Article Date: 02 Aug 2010 - 0:00 PDT
Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by destruction and disappearance of intrahepatic (inside the liver) bile ducts. Multiple causes have been identified including infections, malignancies, autoimmune conditions and adverse effects of medications. The usual course of this condition is variable and many patients with VBDS respond to treatment of the underlying condition and/ or removal of the offending agent. However, others progress to cirrhosis and end stage liver disease requiring liver transplantation.
VBDS is rare in patients with HIV infection, and only one case has been reported in the literature, that of an HIV patient with advanced disease and cytomegalovirus infection. In addition, there are no reports of nevirapine, an anti-retroviral (anti-HIV) drug causing VBDS even though hepatotoxicity is an important side effect of the drug.
A case report published in the World Journal of Gastroenterology describes VBDS secondary to nevirapine use in an HIV-positive, pregnant female. The patient received care at the University of Texas, Memorial Hermann Hospital and the Texas Liver Center in Houston by Dr. Rajan Kochar and colleagues. A 28-yr-old African American female in the 3rd trimester of pregnancy presented to the emergency room with jaundice and itching for 3 days. She also complained of pruritus, light colored stools and dark urine. She was diagnosed with HIV infection in 2000 and had not been on highly active anti-retroviral therapy (HAART) since 2003, but recently started triple drug therapy to minimize risk of vertical transmission with zidovudine, lamivudine and nevirapine 4 wk prior to presentation. She had no history of any opportunistic infections and was not taking any prophylactic medications. Liver tests were abnormal and after liver biopsy was performed, a diagnosis of vanishing bile duct syndrome (VBDS) was made. Liver transplant evaluation was subsequently initiated for the patient.
The most likely cause of VBDS in this patient was drug-induced liver injury (DILI). Nevirapine, a non-nucleoside reverse transcriptase inhibitor, is being increasingly used in pregnant patients owing to its favorable side effect profile and lower teratogenicity compared to protease inhibitors. However, hepatotoxicity is the major adverse effect of nevirapine (5%) and most often manifests as a hypersensitivity reaction with fever, rash and elevated liver tests within the first few weeks of therapy. Late onset hepatotoxicity after several weeks of nevirapine use has also been described in several cases and may be an idiosyncratic reaction to the drug. Although several case reports have demonstrated a cholestatic pattern of nevirapine toxicity, VBDS has never been reported. Ms. B did not have fever and rash, but had evidence of cholestatic hepatitis and a temporal association between nevirapine use and development of biochemical abnormalities. Therefore, nevirapine toxicity was felt to be the most likely cause of cholestasis and VBDS.
To the best of the authors' knowledge, this is the first reported case of nevirapine induced cholestatic hepatitis in a patient with HIV leading to severe ductopenia and VBDS. Therefore, VBDS should be considered in all HIV patients with chronic cholestasis, especially those with a history of nevirapine use. In addition, the possibility of this potentially irreversible adverse event should be kept in mind before making the decision to prescribe nevirapine.
Reference:
Kochar R, Nevah MI, Lukens FJ, Fallon MB, Machicao VI. Vanishing bile duct syndrome in human immunodeficiency virus: Nevirapine hepatotoxicity revisited. World J Gastroenterol 2010; 16(26): 3335-3338
Source:
Lin Tian
World Journal of Gastroenterology
Source
August 2, 2010
A Potential Chemotherapeutic Drug To Treat Hepatocellular Carcinoma
Article Date: 02 Aug 2010 - 0:00 PDT
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, particularly in China. However, HCC remains one of the more difficult cancers to treat. It is important to screen for new anti-cancer drugs. A number of dietary compounds possess anti-cancer properties. These dietary compounds may modify the activity of specific targets that control cell proliferation and apoptosis. Galangin could inhibit the methoxyresorufin O-demethylase activity of CYP1A2, CYP1A1 and P-form phenolsulfotransferase. Galangin induced apoptosis in several cancer cell lines and arrested the cell cycle, modulated the expression of cycline/cdk, and decreased Bcl-2. It was suggested that galangin may be a potential anti-tumor agent. However, the mechanism by which galangin exerts its anti-tumor activity is unknown.
A research article published in the World Journal of Gastroenterology addresses this issue. This is the first study to report that galangin mediates apoptosis through a mitochondrial pathway.
Their data demonstrated that:
Source:
Ye-Ru Wang
World Journal of Gastroenterology
Source
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, particularly in China. However, HCC remains one of the more difficult cancers to treat. It is important to screen for new anti-cancer drugs. A number of dietary compounds possess anti-cancer properties. These dietary compounds may modify the activity of specific targets that control cell proliferation and apoptosis. Galangin could inhibit the methoxyresorufin O-demethylase activity of CYP1A2, CYP1A1 and P-form phenolsulfotransferase. Galangin induced apoptosis in several cancer cell lines and arrested the cell cycle, modulated the expression of cycline/cdk, and decreased Bcl-2. It was suggested that galangin may be a potential anti-tumor agent. However, the mechanism by which galangin exerts its anti-tumor activity is unknown.
A research article published in the World Journal of Gastroenterology addresses this issue. This is the first study to report that galangin mediates apoptosis through a mitochondrial pathway.
Their data demonstrated that:
- galangin induces HCC cell apoptosis by triggering Bax translocation to the mitochondria;
- galangin-treated HCC cells causes the release of AIF and cytochrome c into the cytosol from the mitochondria; and
- overexpression of Bcl-2 attenuated galangin-induced HepG2 cells apoptosis, while down-regulated Bcl-2 expression enhanced galangin to induce cell apoptosis.
Reference:
Zhang HT, Luo H, Wu J, Lan LB, Fan DH, Zhu KD, Chen XY, Wen M, Liu HM. Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol 2010; 16(27): 3377-3384Source:
Ye-Ru Wang
World Journal of Gastroenterology
Source
Effective Inducing Systems Of Hepatic Differentiation From Bone Marrow Mesenchymal Stem Cells
Article Date: 02 Aug 2010 - 1:00 PDT
Recent studies suggest that MSCs possess a greater differentiation potential than once thought and several hepatic differentiation protocols from bone marrow cells have been established. However, the incidence of bone marrow-derived hepatocytes was low. Moreover, a long culture period is needed in most cases.
A research article published in World Journal of Gastroenterology addresses this issue. The research team led by Professor Shao JZ from College of Life Sciences of Zhejiang University used mice to investigate the role of VPA on hepatic differentiation of mBM-MSCs. The article indicates that additional exposure of mBM-MSCs to VPA considerably increased the hepatic differentiation in vitro and improved the liver injury by increased homing efficiency of cells to the damaged site in vivo.
The MSCs were successfully isolated from mouse bone marrow and demonstrated that they could differentiate into hepatocytes induced by VPA and well-defined cytokines in a sequential way. The present study demonstrated that VPA-mediated facilitation of hepatic differentiation was regulated by the selective expression of fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) receptors, the increased amounts of acetylated H3 and H4 as well as the structural de-condensation of chromatin. These results provide new insights into the relationships between the epigenetic modification mediated by VPA and the hepatic differentiation from mBM-MSCs.
These findings may also be applicable to study endoderm differentiation and offers an unlimited source of functional hepatocyte-like cells applicable for pharmaco-toxicological research and testing, also this induced system has numerous potential advantages in clinical application.
Reference:
Dong XJ, Zhang H, Pan RL, Xiang LX, Shao JZ. Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. World J Gastroenterol 2010; 16(26): 3267-3278
Source:
Lin Tian
World Journal of Gastroenterology
Source
Recent studies suggest that MSCs possess a greater differentiation potential than once thought and several hepatic differentiation protocols from bone marrow cells have been established. However, the incidence of bone marrow-derived hepatocytes was low. Moreover, a long culture period is needed in most cases.
A research article published in World Journal of Gastroenterology addresses this issue. The research team led by Professor Shao JZ from College of Life Sciences of Zhejiang University used mice to investigate the role of VPA on hepatic differentiation of mBM-MSCs. The article indicates that additional exposure of mBM-MSCs to VPA considerably increased the hepatic differentiation in vitro and improved the liver injury by increased homing efficiency of cells to the damaged site in vivo.
The MSCs were successfully isolated from mouse bone marrow and demonstrated that they could differentiate into hepatocytes induced by VPA and well-defined cytokines in a sequential way. The present study demonstrated that VPA-mediated facilitation of hepatic differentiation was regulated by the selective expression of fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) receptors, the increased amounts of acetylated H3 and H4 as well as the structural de-condensation of chromatin. These results provide new insights into the relationships between the epigenetic modification mediated by VPA and the hepatic differentiation from mBM-MSCs.
These findings may also be applicable to study endoderm differentiation and offers an unlimited source of functional hepatocyte-like cells applicable for pharmaco-toxicological research and testing, also this induced system has numerous potential advantages in clinical application.
Reference:
Dong XJ, Zhang H, Pan RL, Xiang LX, Shao JZ. Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. World J Gastroenterol 2010; 16(26): 3267-3278
Source:
Lin Tian
World Journal of Gastroenterology
Source
Exciting Changes to Scientific Program at The Liver Meeting® 2010
AASLD News: July 29, 2010
By Arun J. Sanyal, MD, AASLD President
This year’s Liver Meeting® received a record-breaking number of abstracts and registration is now open. I recently had the opportunity to meet with the Scientific Program Committee and put the scientific program together for the meeting and would like to share my excitement and provide a preview of some of the offerings at The Liver Meeting® which make this the premier meeting related to liver diseases worldwide.
Hepatitis at the Liver Meeting
This year, the Postraduate Course will focus on viral hepatitis. This course is also extraordinarily timely given the intense interest generated by the Institute of Medicine (IOM) report and the follow up actions by AASLD outlined previously in this column. The Presidents Choice Lecture will be delivered by the honorable Dr. Howard Koh, Assistant Secretary of Health, United States government, who will outline federal initiatives to translate the IOM report into a plan to control the burden of viral hepatitis in the United States. These talks will be complemented by the clinical Leon Schiff State-of-the-Art Lecture, to be delivered by Dr. David Goldstein, on how recent advances in the genetic determinants of treatment response may allow tailoring treatment to the individual.
Clinical Trials
Several large clinical trials will be presented that are likely to be game changers in the practice of hepatology. These include the final results of telaprevir with interferon and ribavirin (ADVANCE trial), and the use of Boceprevir in non-responders or relapsers to first-line therapy for hepatitis C. The final results of the TONIC trial of metformin or vitamin E versus placebo for NAFLD in children performed by the NIDDK NASH Clinical Research Network will also be presented and will have a major impact on the future management of this disease both in children and in adults.
Cancer as a Theme
A major theme to emerge this year relates to liver cancer. The Liver Cancer Special Interest Group (SIG) will host a symposium on cholangiocarcinoma to highlight the burning issues in the field. A detailed molecular classification of cholangiocarcinoma with specific clinical implications will also be presented in a plenary session. Also, a number of scientific advances in the understanding of the molecular pathogenesis of hepatocellular cancer will be presented. These will synergize with a special session on stem cells and their role in neoplastic transformation in the liver. The Thomas E. Starzl Transplant Surgery State-of-the-Art Lecture will be given by Dr. Michael Abecassis who will discuss the role of liver transplantation in the management of liver cancer.
State-of-the-Art Lectures
In addition to the aforementioned Schiff and Starzl State-of-the-Art Lectures, the Hyman Zimmerman Hepatotoxicity State-of-the-Art Lecture will be delivered by Gyongi Szabo, MD, PhD, on the role of innate immunity in modulating liver injury and the high-quality science in the areas of cell signaling and cell biology that have broad implications for both a healthy liver and a wide range of liver diseases. This is complemented by three sessions on nonalcoholic steatohepatitis and alcohol-related liver disease – an increase from the one session at last year’s meeting and based on the exceptionally high quality of science that was submitted.
The role of bile acids in hepatic physiology has been recognized for many decades. It is now recognized that the process of enterohepatic circulation of bile acids sends signals to the rest of the body about the availability of nutrition from the gut and the cross talk between the intestine and liver via bile acid signaling plays a central role in nutritional homeostasis. The cellular mechanisms of how this is accomplished will be the focus of the Hans Popper Basic Science State-of-the-Art Lecture to be delivered by Prof. Johann Auwerx. This information will be particularly relevant for everyone interested in the current epidemic of obesity, diabetes, and fatty liver disease.
A Focus on Clinicians and Surgeons
For the practicing clinician, the offerings will continue to increase with the General Hepatology Update, a selection of early morning sessions, clinical symposia on liver cancer, portal hypertension, and a new session called the Hepatitis Debrief, which will place all of the new information presented at the liver meeting in perspective. Another new feature at The Liver Meeting® is the Emerging Trends Symposium, which will focus on advances in imaging in liver diseases with a focus on the imaging of tumors, assessment of fibrosis, and measurement of hepatic venous pressure gradient. Similarly, for our surgical colleagues, a workshop on split liver transplantation, donor related issues, the role of genetics in determining post transplant outcomes for those with hepatitis C, and engineering a transplantable liver are just some of the highlights.
These are only some of the many novel and innovative scientific advances in hepatology that will be presented at The Liver Meeting®. There is no question that the scientific and clinical content of the meeting will exceed your expectations and I hope to see you all in Boston to celebrate the best that the field has to offer.
This electronic newsletter is a bi-weekly publication of AASLD and replaces the former bi-monthly print newsletter and weekly e-news. Members are welcome to submit articles and may send suggestions to aharan@aasld.org.
Source
By Arun J. Sanyal, MD, AASLD President
This year’s Liver Meeting® received a record-breaking number of abstracts and registration is now open. I recently had the opportunity to meet with the Scientific Program Committee and put the scientific program together for the meeting and would like to share my excitement and provide a preview of some of the offerings at The Liver Meeting® which make this the premier meeting related to liver diseases worldwide.
Hepatitis at the Liver Meeting
This year, the Postraduate Course will focus on viral hepatitis. This course is also extraordinarily timely given the intense interest generated by the Institute of Medicine (IOM) report and the follow up actions by AASLD outlined previously in this column. The Presidents Choice Lecture will be delivered by the honorable Dr. Howard Koh, Assistant Secretary of Health, United States government, who will outline federal initiatives to translate the IOM report into a plan to control the burden of viral hepatitis in the United States. These talks will be complemented by the clinical Leon Schiff State-of-the-Art Lecture, to be delivered by Dr. David Goldstein, on how recent advances in the genetic determinants of treatment response may allow tailoring treatment to the individual.
Clinical Trials
Several large clinical trials will be presented that are likely to be game changers in the practice of hepatology. These include the final results of telaprevir with interferon and ribavirin (ADVANCE trial), and the use of Boceprevir in non-responders or relapsers to first-line therapy for hepatitis C. The final results of the TONIC trial of metformin or vitamin E versus placebo for NAFLD in children performed by the NIDDK NASH Clinical Research Network will also be presented and will have a major impact on the future management of this disease both in children and in adults.
Cancer as a Theme
A major theme to emerge this year relates to liver cancer. The Liver Cancer Special Interest Group (SIG) will host a symposium on cholangiocarcinoma to highlight the burning issues in the field. A detailed molecular classification of cholangiocarcinoma with specific clinical implications will also be presented in a plenary session. Also, a number of scientific advances in the understanding of the molecular pathogenesis of hepatocellular cancer will be presented. These will synergize with a special session on stem cells and their role in neoplastic transformation in the liver. The Thomas E. Starzl Transplant Surgery State-of-the-Art Lecture will be given by Dr. Michael Abecassis who will discuss the role of liver transplantation in the management of liver cancer.
State-of-the-Art Lectures
In addition to the aforementioned Schiff and Starzl State-of-the-Art Lectures, the Hyman Zimmerman Hepatotoxicity State-of-the-Art Lecture will be delivered by Gyongi Szabo, MD, PhD, on the role of innate immunity in modulating liver injury and the high-quality science in the areas of cell signaling and cell biology that have broad implications for both a healthy liver and a wide range of liver diseases. This is complemented by three sessions on nonalcoholic steatohepatitis and alcohol-related liver disease – an increase from the one session at last year’s meeting and based on the exceptionally high quality of science that was submitted.
The role of bile acids in hepatic physiology has been recognized for many decades. It is now recognized that the process of enterohepatic circulation of bile acids sends signals to the rest of the body about the availability of nutrition from the gut and the cross talk between the intestine and liver via bile acid signaling plays a central role in nutritional homeostasis. The cellular mechanisms of how this is accomplished will be the focus of the Hans Popper Basic Science State-of-the-Art Lecture to be delivered by Prof. Johann Auwerx. This information will be particularly relevant for everyone interested in the current epidemic of obesity, diabetes, and fatty liver disease.
A Focus on Clinicians and Surgeons
For the practicing clinician, the offerings will continue to increase with the General Hepatology Update, a selection of early morning sessions, clinical symposia on liver cancer, portal hypertension, and a new session called the Hepatitis Debrief, which will place all of the new information presented at the liver meeting in perspective. Another new feature at The Liver Meeting® is the Emerging Trends Symposium, which will focus on advances in imaging in liver diseases with a focus on the imaging of tumors, assessment of fibrosis, and measurement of hepatic venous pressure gradient. Similarly, for our surgical colleagues, a workshop on split liver transplantation, donor related issues, the role of genetics in determining post transplant outcomes for those with hepatitis C, and engineering a transplantable liver are just some of the highlights.
These are only some of the many novel and innovative scientific advances in hepatology that will be presented at The Liver Meeting®. There is no question that the scientific and clinical content of the meeting will exceed your expectations and I hope to see you all in Boston to celebrate the best that the field has to offer.
This electronic newsletter is a bi-weekly publication of AASLD and replaces the former bi-monthly print newsletter and weekly e-news. Members are welcome to submit articles and may send suggestions to aharan@aasld.org.
Source
Incidence of Non-AIDS-Related Cancers Increasing Among People With HIV
Norra MacReady
August 2, 2010 (Vienna, Austria) — Life expectancy is increasing for people with HIV and AIDS, and with it, cancer risk and incidence, Eric A. Engels, MD, MPH, reported here at AIDS 2010: XVIII International AIDS Conference.
This means that cancer prevention and treatment among people infected with HIV will become more and more important in the years ahead, said Dr. Engels, senior investigator at the Division of Cancer Epidemiology and Genetics at the National Cancer Institute.
In an analysis of data collected by the Centers for Disease Control and Prevention during 15 years from 15 regions of the United States, Dr. Engels and coauthors found that the proportion of the US AIDS population aged 50 years or more increased from 8% of 93,802 people in 1991 to 29% of 399,762 people in 2005.
During the same time period, the incidence of non-AIDS-defining cancers increased, from 416 in 1991 to 2437 in 2005, with a total of 76,558 cancers in this cohort.
In contrast, AIDS-defining cancers such as Kaposi's sarcoma and non-Hodgkin's lymphoma decreased from 7284 cases in 1993 to 1736 cases in 2005.
Cases of anal cancer increased from 18 in 1991 to 358 in 2005, and cases of prostate cancer increased from 10 to 123 from 1991 to 2005, largely as a result of rising rates of those malignancies, Dr. Engels said during an oral abstract session. The rates of lung cancer and Hodgkin's lymphoma remained relatively stable, but the absolute number of cases increased from 112 to 478 and from 72 to 169, respectively.
The authors also estimated cancer incidence between 2004 and 2007 for people in 34 states who were HIV-positive but did not have AIDS. In that population, 4388 cancers occurred, including 381 anal cancers, 892 lung cancers, and 327 cases of Hodgkin's lymphoma.
Immunosuppression and coinfection with the human papillomavirus may explain, in part, the dramatic rise in the number of anal cancer cases, Dr. Engels told Medscape Medical News.
These findings are "in large part due to the increasing number of people living with HIV infection and the fact that they are getting older," he said. "Non-AIDS-defining cancers are now roughly as common as AIDS-defining cancers [in this population] and represent a priority for cancer prevention, screening, and treatment."
Treatment challenges among people with HIV and AIDS include immunosuppression and drug interactions between highly active antiretroviral therapy and chemotherapy. In addition, "many HIV-infected people present late to care, which can impair their response to cancer treatment," the investigator pointed out.
Strides in medications and management are allowing patients in this population "to enter the prime years for cancer development," noted Susan E. Krown, MD, head of the Human Papilloma Virus Working Group of the AIDS Malignancy Consortium at the National Cancer Institute.
Patients infected with HIV "are also more likely than HIV-uninfected individuals to smoke and to have coinfections, such as HPV and hepatitis B and C, that increase the likelihood of certain cancers. A particular challenge is to learn how best to manage the sometimes profound interactions between cancer therapeutic agents and antiretroviral drugs," said Dr. Krown, who is also a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City. She was not involved in this research.
"The link between non-AIDS-defining cancers and HIV is not entirely clear, but appears to be related to factors beyond HIV and the associated immunosuppression," said Michael Fisch, MD, MPH, chairman of the Department of General Oncology at the M.D. Anderson Cancer Center in Houston, Texas. Along with lifestyle factors such as smoking and sexual behavior, "testosterone replacement, and perhaps even adherence to screening recommendations, may play a role in the association" between HIV and non-AIDS-defining cancers, he added. Dr. Fisch was also not involved in this study.
He took a brighter view of treatment than Dr. Krown. "In most instances, standard cancer therapy can be safely provided to HIV-infected patients," he told Medscape Medical News. "And I am optimistic that similar potential exists for the HIV population to reduce suffering and death due to cancer through standard screening and advice related to lifestyle and behavioral modifications."
Dr. Engels, Dr. Krown, and Dr. Fisch have disclosed no relevant financial relationships.
AIDS 2010: XVIII International AIDS Conference: Abstract WEAB 0101. Presented Wednesday, July 21, 2010
Source
August 2, 2010 (Vienna, Austria) — Life expectancy is increasing for people with HIV and AIDS, and with it, cancer risk and incidence, Eric A. Engels, MD, MPH, reported here at AIDS 2010: XVIII International AIDS Conference.
This means that cancer prevention and treatment among people infected with HIV will become more and more important in the years ahead, said Dr. Engels, senior investigator at the Division of Cancer Epidemiology and Genetics at the National Cancer Institute.
In an analysis of data collected by the Centers for Disease Control and Prevention during 15 years from 15 regions of the United States, Dr. Engels and coauthors found that the proportion of the US AIDS population aged 50 years or more increased from 8% of 93,802 people in 1991 to 29% of 399,762 people in 2005.
During the same time period, the incidence of non-AIDS-defining cancers increased, from 416 in 1991 to 2437 in 2005, with a total of 76,558 cancers in this cohort.
In contrast, AIDS-defining cancers such as Kaposi's sarcoma and non-Hodgkin's lymphoma decreased from 7284 cases in 1993 to 1736 cases in 2005.
Cases of anal cancer increased from 18 in 1991 to 358 in 2005, and cases of prostate cancer increased from 10 to 123 from 1991 to 2005, largely as a result of rising rates of those malignancies, Dr. Engels said during an oral abstract session. The rates of lung cancer and Hodgkin's lymphoma remained relatively stable, but the absolute number of cases increased from 112 to 478 and from 72 to 169, respectively.
The authors also estimated cancer incidence between 2004 and 2007 for people in 34 states who were HIV-positive but did not have AIDS. In that population, 4388 cancers occurred, including 381 anal cancers, 892 lung cancers, and 327 cases of Hodgkin's lymphoma.
Immunosuppression and coinfection with the human papillomavirus may explain, in part, the dramatic rise in the number of anal cancer cases, Dr. Engels told Medscape Medical News.
These findings are "in large part due to the increasing number of people living with HIV infection and the fact that they are getting older," he said. "Non-AIDS-defining cancers are now roughly as common as AIDS-defining cancers [in this population] and represent a priority for cancer prevention, screening, and treatment."
Treatment challenges among people with HIV and AIDS include immunosuppression and drug interactions between highly active antiretroviral therapy and chemotherapy. In addition, "many HIV-infected people present late to care, which can impair their response to cancer treatment," the investigator pointed out.
Strides in medications and management are allowing patients in this population "to enter the prime years for cancer development," noted Susan E. Krown, MD, head of the Human Papilloma Virus Working Group of the AIDS Malignancy Consortium at the National Cancer Institute.
Patients infected with HIV "are also more likely than HIV-uninfected individuals to smoke and to have coinfections, such as HPV and hepatitis B and C, that increase the likelihood of certain cancers. A particular challenge is to learn how best to manage the sometimes profound interactions between cancer therapeutic agents and antiretroviral drugs," said Dr. Krown, who is also a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City. She was not involved in this research.
"The link between non-AIDS-defining cancers and HIV is not entirely clear, but appears to be related to factors beyond HIV and the associated immunosuppression," said Michael Fisch, MD, MPH, chairman of the Department of General Oncology at the M.D. Anderson Cancer Center in Houston, Texas. Along with lifestyle factors such as smoking and sexual behavior, "testosterone replacement, and perhaps even adherence to screening recommendations, may play a role in the association" between HIV and non-AIDS-defining cancers, he added. Dr. Fisch was also not involved in this study.
He took a brighter view of treatment than Dr. Krown. "In most instances, standard cancer therapy can be safely provided to HIV-infected patients," he told Medscape Medical News. "And I am optimistic that similar potential exists for the HIV population to reduce suffering and death due to cancer through standard screening and advice related to lifestyle and behavioral modifications."
Dr. Engels, Dr. Krown, and Dr. Fisch have disclosed no relevant financial relationships.
AIDS 2010: XVIII International AIDS Conference: Abstract WEAB 0101. Presented Wednesday, July 21, 2010
Source
The Next Pandemic
Author
Jeffrey Fried
Hepatitis C (HCV) is the next pandemic. 250-300 million people worldwide are carrying the virus. This is 5, five, times the number of people carrying HIV. HCV is the main cause for liver transplants. As of a few years ago, for every 20 people who die of HIV in the US, 11 people die of HCV because they cannot get a liver transplant. And what makes it particularly dangerous is that when contracting HCV the symptoms are usually mild, or none at all, and there are no obvious symptoms until 20 years later when the liver starts to fail. This means that people are giving the disease to other people simply because they don't know that they have it, so, they don't know what they should do to prevent transmitting it to others. Also, the period where most people appear to be without symptoms, is in fact not the case. During that time some people develop related disorders (http://www.webmd.com/hepatitis/connection-between-hepatitis-c-autoimmune-disorders) that can be very debilitating.
Currently the only drug therapy, interferon, works about 50% of the time for those who can afford it. It requires loading your body with interferon, the same chemical that your body uses to kill colds, and other viruses, producing the same side effects for 26 to 52 weeks. The cost of the therapy can be prohibitive for people with low income or no health insurance.
Surprisingly the effort needed to protect yourself is relatively simple, its just that most of us are unaware so we don't take any precautions. The story should explain the problem, present current, and emerging therapies, and provide a sense of what the reader should do to ensure that they are not carriers or receivers.
Source
Jeffrey Fried
Hepatitis C (HCV) is the next pandemic. 250-300 million people worldwide are carrying the virus. This is 5, five, times the number of people carrying HIV. HCV is the main cause for liver transplants. As of a few years ago, for every 20 people who die of HIV in the US, 11 people die of HCV because they cannot get a liver transplant. And what makes it particularly dangerous is that when contracting HCV the symptoms are usually mild, or none at all, and there are no obvious symptoms until 20 years later when the liver starts to fail. This means that people are giving the disease to other people simply because they don't know that they have it, so, they don't know what they should do to prevent transmitting it to others. Also, the period where most people appear to be without symptoms, is in fact not the case. During that time some people develop related disorders (http://www.webmd.com/hepatitis/connection-between-hepatitis-c-autoimmune-disorders) that can be very debilitating.
Currently the only drug therapy, interferon, works about 50% of the time for those who can afford it. It requires loading your body with interferon, the same chemical that your body uses to kill colds, and other viruses, producing the same side effects for 26 to 52 weeks. The cost of the therapy can be prohibitive for people with low income or no health insurance.
Surprisingly the effort needed to protect yourself is relatively simple, its just that most of us are unaware so we don't take any precautions. The story should explain the problem, present current, and emerging therapies, and provide a sense of what the reader should do to ensure that they are not carriers or receivers.
Source
New study to turn cancer research on its head
David Binning (Australian Life Scientist)
02 August, 2010 16:30
Research challenges conventional wisdom that cell death impedes tumour growth
Researchers at the Walter and Eliza Hall Institute (WEHI) have shown that programmed cell death or apoptosis, a process which has typically been assumed to prevent or slow the development of cancer, may in some instances contribute to its spreading.
“In general everything we’ve known indicates that if you have impaired cell death that helps the tumour to get going,” Professor Jerry Adams told Australian Life Scientist. “What’s exciting about this result is it’s the first case in which the opposite happens.”
For example, when the DNA in many cells is damaged, as occurs after repeated exposure to low doses of radiation, this leads to repeated cycles of cell death in the body’s tissues.
“Attempts by the body’s stem cells to repopulate the depleted tissue can then actually drive the tumour development,” project leader Professor Andreas Strasser said.
“That’s because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours.”
A particular focus of the teams’ research was comparing the effects of radiation exposure in mice with and without the so-called Puma gene, which is essential for the death of cells with damaged DNA.
“If normal mice (which have the Puma gene) are given a low dose of radiation it destroys around 80 per cent of the white blood cells,” Professor Strasser said. “That does not kill the mouse but it does mean the stem cells in the bone marrow have to work extra hard to replenish the blood system. This can lead to the formation of tumours of white blood cells, called leukaemia’s, if the stem cells doing the re-populating have cancer-causing mutations."
In contrast, mice without the Puma gene did no experience this type of tumour development at all.
“If mice don’t have the Puma gene when they receive low doses of radiation the white blood cells are not destroyed, so you don’t force mutated stem cells to become activated (and divide) to replenish the blood system,” Professor Strasser explained.
The findings point to an increased risk of cancer development in people who have experienced cycles of cell damage followed by tissue re-population by stem cells. Examples include liver cancers such as those arising from viral infections like hepatitis C, or alcohol-related liver damage. The research may also help to shed light on the causes of secondary cancers which can appear in patients cured of their primary cancer by chemotherapy drugs which typically result in damaged DNA.
Further, these findings are expected to lead to a deeper understanding of the role and effectiveness of the new class of BH3 mimetics cancer drugs, which are designed to kill cancer cells.
Professor Adams said that the study results would likely be of interest to Abbot Laboratories, which is currently conducting similar research into cancer treatments. Abbott and the WEHI have a research collaboration agreement.
Funding for the WEHI study was provided by the National Health and Medical Research Council, the Leukaemia and Lymphoma Society, the National Institutes of Health (US), the Juvenile Diabetes Research Foundation, Cancer Council Victoria and the Victorian Government.
The complete findings were published this week in the international journal Genes and Development.
Source
02 August, 2010 16:30
Research challenges conventional wisdom that cell death impedes tumour growth
Researchers at the Walter and Eliza Hall Institute (WEHI) have shown that programmed cell death or apoptosis, a process which has typically been assumed to prevent or slow the development of cancer, may in some instances contribute to its spreading.
“In general everything we’ve known indicates that if you have impaired cell death that helps the tumour to get going,” Professor Jerry Adams told Australian Life Scientist. “What’s exciting about this result is it’s the first case in which the opposite happens.”
For example, when the DNA in many cells is damaged, as occurs after repeated exposure to low doses of radiation, this leads to repeated cycles of cell death in the body’s tissues.
“Attempts by the body’s stem cells to repopulate the depleted tissue can then actually drive the tumour development,” project leader Professor Andreas Strasser said.
“That’s because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours.”
A particular focus of the teams’ research was comparing the effects of radiation exposure in mice with and without the so-called Puma gene, which is essential for the death of cells with damaged DNA.
“If normal mice (which have the Puma gene) are given a low dose of radiation it destroys around 80 per cent of the white blood cells,” Professor Strasser said. “That does not kill the mouse but it does mean the stem cells in the bone marrow have to work extra hard to replenish the blood system. This can lead to the formation of tumours of white blood cells, called leukaemia’s, if the stem cells doing the re-populating have cancer-causing mutations."
In contrast, mice without the Puma gene did no experience this type of tumour development at all.
“If mice don’t have the Puma gene when they receive low doses of radiation the white blood cells are not destroyed, so you don’t force mutated stem cells to become activated (and divide) to replenish the blood system,” Professor Strasser explained.
The findings point to an increased risk of cancer development in people who have experienced cycles of cell damage followed by tissue re-population by stem cells. Examples include liver cancers such as those arising from viral infections like hepatitis C, or alcohol-related liver damage. The research may also help to shed light on the causes of secondary cancers which can appear in patients cured of their primary cancer by chemotherapy drugs which typically result in damaged DNA.
Further, these findings are expected to lead to a deeper understanding of the role and effectiveness of the new class of BH3 mimetics cancer drugs, which are designed to kill cancer cells.
Professor Adams said that the study results would likely be of interest to Abbot Laboratories, which is currently conducting similar research into cancer treatments. Abbott and the WEHI have a research collaboration agreement.
Funding for the WEHI study was provided by the National Health and Medical Research Council, the Leukaemia and Lymphoma Society, the National Institutes of Health (US), the Juvenile Diabetes Research Foundation, Cancer Council Victoria and the Victorian Government.
The complete findings were published this week in the international journal Genes and Development.
Source
Thousands may not know they have fatal blood infections
THOUSANDS of people in Nottingham could have potentially fatal infections such as hepatitis and HIV – but not know it.
The NHS says as many as 3,000 people in the city may have one or more blood-borne infections.
Hepatitis B and C and HIV can be spread though sex with an infected person, sharing needles or through a broken area of skin.
And 80% of sufferers – around 2,400 people – may not know they have them.
GPs are now routinely testing "at-risk" people from countries with high rates of blood-borne viruses, those who inject drugs or the sexual partners of sufferers.
And experts are calling for people in such groups to get themselves tested – to avoid putting themselves and others at risk.
Mick Mason of sexual health charity the Terrence Higgins Trust said those at risk should get tested as early as possible. "The earlier you can get people diagnosed, the less risk there is of passing it on," he said.
People can get test results for HIV within 20 minutes and for hepatitis B and C within a week from the charity's base at Barker Gate, the Lace Market.
The number of people thought to have HIV has risen sharply in recent years, with 428 new cases in 2007.
Infections rates have gone up in Nottingham due, in part, to people from countries with higher rates of blood-borne viruses coming to the city.
Hepatitis B and C are infections of the liver caused by a virus, which can cause significant damage if left untreated.
Human immunodeficiency virus (HIV) is a virus that attacks the body's immune system. It leaves an infected person with a high risk of developing a serious infection or disease, such as cancer.
Mr Mason contracted HIV as well as Hepatitis B and C in 1983 from contaminated blood plasma. "We do see more and more cases of cross-infection, when someone has hepatitis and HIV," he said.
"That is an added complication because the two conditions accelerate each other and the treatments have an adverse effect on the other condition."
The rise in the number of blood-borne virus cases was revealed in the annual report of the primary care trust's director of public health, Chris Packham.
Source
The NHS says as many as 3,000 people in the city may have one or more blood-borne infections.
Hepatitis B and C and HIV can be spread though sex with an infected person, sharing needles or through a broken area of skin.
And 80% of sufferers – around 2,400 people – may not know they have them.
GPs are now routinely testing "at-risk" people from countries with high rates of blood-borne viruses, those who inject drugs or the sexual partners of sufferers.
And experts are calling for people in such groups to get themselves tested – to avoid putting themselves and others at risk.
Mick Mason of sexual health charity the Terrence Higgins Trust said those at risk should get tested as early as possible. "The earlier you can get people diagnosed, the less risk there is of passing it on," he said.
People can get test results for HIV within 20 minutes and for hepatitis B and C within a week from the charity's base at Barker Gate, the Lace Market.
The number of people thought to have HIV has risen sharply in recent years, with 428 new cases in 2007.
Infections rates have gone up in Nottingham due, in part, to people from countries with higher rates of blood-borne viruses coming to the city.
Hepatitis B and C are infections of the liver caused by a virus, which can cause significant damage if left untreated.
Human immunodeficiency virus (HIV) is a virus that attacks the body's immune system. It leaves an infected person with a high risk of developing a serious infection or disease, such as cancer.
Mr Mason contracted HIV as well as Hepatitis B and C in 1983 from contaminated blood plasma. "We do see more and more cases of cross-infection, when someone has hepatitis and HIV," he said.
"That is an added complication because the two conditions accelerate each other and the treatments have an adverse effect on the other condition."
The rise in the number of blood-borne virus cases was revealed in the annual report of the primary care trust's director of public health, Chris Packham.
Source
Conquering HIV, hepatitis C requires ongoing research, expert says
Publish date: Aug 1, 2010
By: John Jesitus
Key Points
By: John Jesitus
Key Points
- More than a dozen drug candidates under development for HCV
- Researchers are applying combination modalities established in cancer and HIV to HCV
Atlanta — Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may be out of the public eye, but curing these unseen epidemics requires ongoing research, says an expert who spoke at the 2010 annual meeting of the Society for Investigative Dermatology.
Although more than two dozen HIV drugs can alleviate suffering and prolong life, "The epidemic is not over," says Raymond Schinazi, Ph.D., D.Sc., professor of pediatrics, Emory University School of Medicine and Atlanta VA Medical Center. "We also know that more than 1 million people have been infected with HIV in the United States," and an estimated 60 million will be infected worldwide by 2015, he says, adding that only 28 percent of those who need treatment actually get it.
Before the advent of modern treatments in 1985, HIV had a 73 percent mortality rate, Dr. Schinazi says. But by 2008, more than 94 percent of people infected with HIV who receive Western standard-of-care treatment survive at least five years.
"More than 90 percent of HIV-infected subjects are taking one or more drugs invented at Emory University," he says. Examples include Atripla (efavirenz 600 mg, emtricitabine 200 mg, tenofovir-DF 300 mg; Bristol-Myers Squibb/Gilead), 3TC (beta-2',3'-dideoxy-3'-thiacytidine, also called Lamivudine; GlaxoSmithKline), Truvada (tenofovir-DF 300 mg/emtricitabine 200 mg, Gilead) and Viread (tenofovir-DF 300 mg, Gilead). As a professor of pediatrics, Dr. Schinazi says, "Probably the most important accomplishment is the fact that maternal-to-fetal transmission today is history. We rarely see it in the United States, although it still occurs in Africa" and elsewhere.
Hepatitis C
For hepatitis C virus (HCV), "We only have two drugs — ribavirin and interferon (IFN). Both are relatively toxic," Dr. Schinazi says. About 280 million people worldwide are infected with HCV. "There are 3 to 4 million infections per year globally, and we expect more than 800,000 U.S. patients to develop HCV-related cirrhosis this decade," he says.
Up to one-third of those with HCV are coinfected with HIV, Dr. Schinazi says, adding that coinfection complicates treatment because physicians must consider dangerous drug interactions. Both viruses share routes of transmission, which are all very dynamic.
"The number of patients with HCV treated in the United States is very small compared to the number of chronic carriers," Dr. Schinazi says. Treatment failures are common, he says, because the current standard of care does not work well against certain HCV genotypes. Only 30 to 60 percent of patients achieve sustained virological response (SVR, or a cure) on currently available HCV therapies, all of which require intravenous administration, he says.
Up-and-coming drugs
More than a dozen drug candidates are under development for HCV (Sarrazin C, Zeuzem S. Gastroenterology. 2010 Feb;138(2):447-462. Epub 2009 Dec 16. Review), Dr. Schinazi says. These include small molecules and interferon-related therapies.
"There are various classes of compounds, including nucleoside and non-nucleoside polymerase inhibitors, cyclophilin inhibitors, protease inhibitors (PIs) and, more recently, the very potent NS5A inhibitors," he says.
However, Dr. Schinazi says, only two candidates are in Food and Drug Administration phase 3 trials: telaprevir (Vertex) and boceprevir (Merck/Schering-Plough). "These PIs are having a remarkable effect on viral load in persons infected with HCV," he says. NS5A inhibitors also show promise in reducing viral load, though they're only in phase 1/2.
HCV drug candidates often fail, Dr. Schinazi says, due to side effects such as anemia, gastrointestinal issues, body composition changes or dermatologic side effects. Telaprevir can cause severe rashes, he notes, a fact which "probably should have been picked up in earlier development. Unfortunately, it wasn't," which has required investigators to cut the treatment duration from six or 12 months to 12 weeks.
HIV updates
People infected with HIV also can experience various dermatologic manifestations. Some, such as psoriasis, are associated with declining CD4 T cell counts, Dr. Schinazi says. Others — eczema/dermatitis, Kaposi's sarcoma, warts — occur despite adequate treatment. Still others, such as lichen planus, occur commonly with HIV-HCV coinfection.
Nevertheless, modern HIV therapies have simplified the complex multi-pill regimens of the 1980s and 1990s into a single pill with three active ingredients (Atripla, Truvada), which frequently achieves strong virus suppression. Meanwhile, Dr. Schinazi says, researchers are applying the combination modalities that have been established in cancer and HIV to HCV.
Researchers also must address HIV's persistence, he says. Even after extensive treatment, the virus rebounds without continued treatment, or when resistance develops. Additionally, persons on successful long-term treatment can experience "blips" wherein viral load climbs from undetectable levels to detectable levels. "Even one virus is enough to light the fire again and cause problems with reinfection (Pierson T, McArthur J, Siliciano RF. Annu Rev Immunol. 2000;18:665-708)," Dr. Schinazi says.
Researchers believe HIV's persistence stems at least partly from anatomical and cellular reservoirs of virus (in areas such as the gut or the brain) where current drugs cannot penetrate effectively, and from ongoing low-level replication. Accordingly, Dr. Schinazi says eradicating HIV will require systematic study of drug penetration into various compartments and its impact on local viral replication.
"Tissue macrophages are a major reservoir for HIV, in addition to the active and memory CD4+ T lymphocytes in the peripheral circulation," he says. En route to developing therapies that can eradicate HIV, Dr. Schinazi says, "We must develop systems to measure virus below current detection levels." Additionally, he says that researchers need preclinical tools that can identify and validate specific biochemical targets and rapidly screen drug candidates, perhaps using cell lines and/or primary cell assays.
Study details
In a recent study, Dr. Schinazi and his coauthors showed that after highly active antiretroviral therapy, viral "sanctuaries" persisted, with the highest levels of viral DNA and RNA found in the spleen, lymph nodes and gastrointestinal tract (North TW, Higgins J, Deere JD, et al. J Virol. 2010 Mar;84(6):2913-2922. Epub 2009 Dec 23).
For eradicating latent integrated HIV, he says the "shock and kill" strategy involves activating the virus and then stimulating it, leading to cell death (Hamer DH. Curr HIV Res. 2004 Apr;2(2):99-111). "The challenges are, how do we specifically kill the cells that are latently infected and deliver the drugs or deadly punch to initiate the cell apoptosis?" Dr. Schinazi says. Other potential approaches involve using anti-TNF-alpha treatment. "That will also be tested in the animal system we have developed."
In combating HCV, Dr. Schinazi says researchers have an advantage, because this virus does not establish latency. "Theoretically, we can eradicate this virus much more easily than HIV." Here, a promising drug candidate under development is a nucleoside developed at Emory in conjunction with Pharmasset, called R7128 (Roche). "The advantage of this nucleoside is that even when there is resistant virus, it is still active," he says.
In clinical testing, investigators combined R7128 (500 mg to 1,500 mg daily) with IFN and ribavirin for 28 days. "Preliminary results showed we had 85 percent rapid virological response in four weeks," Dr. Schinazi says. Researchers then combined the drug in doses of 500 mg or 1,000 mg daily with a PI (R7227, Roche; 100 mg or 200 mg daily) in an attempt to develop an IFN/ribavirin-free regimen.
"By day 14 there was a nearly five log10 drop irrespective of the dose (Gane EJ, Stedman C. First-in-man demonstration of potent antiviral activity with a nucleoside polymerase (R7128) and protease (R7227/ITMN-191) inhibitor combination in HCV: Safety, pharmacokinetics, and virologic results from INFORM-1 [abstract]. J Hepatol. 2008;50 (Suppl. 1): Abstract 1046, S380). Unfortunately, the PI caused some toxicity, so the dose has now been reduced to 100 mg daily, with a protease booster, a bit like we do with HIV," Dr. Schinazi says.
"This is where the future lies — the INFORM study demonstrated that two compounds with different targets can achieve tremendous viral reduction," he says. With HCV, "Cures are already possible with IFN and ribavirin. We just need to improve the SVR." He predicts that in the next year or so, drug combinations will provide SVR for more than 90 percent of patients with HCV.
Disclosures: Dr. Schinazi is founder and major shareholder of Pharmasset, Idenix and RFS Pharma. He also receives royalties from 3TC and LdT.
Source
People infected with HIV also can experience various dermatologic manifestations. Some, such as psoriasis, are associated with declining CD4 T cell counts, Dr. Schinazi says. Others — eczema/dermatitis, Kaposi's sarcoma, warts — occur despite adequate treatment. Still others, such as lichen planus, occur commonly with HIV-HCV coinfection.
Nevertheless, modern HIV therapies have simplified the complex multi-pill regimens of the 1980s and 1990s into a single pill with three active ingredients (Atripla, Truvada), which frequently achieves strong virus suppression. Meanwhile, Dr. Schinazi says, researchers are applying the combination modalities that have been established in cancer and HIV to HCV.
Researchers also must address HIV's persistence, he says. Even after extensive treatment, the virus rebounds without continued treatment, or when resistance develops. Additionally, persons on successful long-term treatment can experience "blips" wherein viral load climbs from undetectable levels to detectable levels. "Even one virus is enough to light the fire again and cause problems with reinfection (Pierson T, McArthur J, Siliciano RF. Annu Rev Immunol. 2000;18:665-708)," Dr. Schinazi says.
Researchers believe HIV's persistence stems at least partly from anatomical and cellular reservoirs of virus (in areas such as the gut or the brain) where current drugs cannot penetrate effectively, and from ongoing low-level replication. Accordingly, Dr. Schinazi says eradicating HIV will require systematic study of drug penetration into various compartments and its impact on local viral replication.
"Tissue macrophages are a major reservoir for HIV, in addition to the active and memory CD4+ T lymphocytes in the peripheral circulation," he says. En route to developing therapies that can eradicate HIV, Dr. Schinazi says, "We must develop systems to measure virus below current detection levels." Additionally, he says that researchers need preclinical tools that can identify and validate specific biochemical targets and rapidly screen drug candidates, perhaps using cell lines and/or primary cell assays.
Study details
In a recent study, Dr. Schinazi and his coauthors showed that after highly active antiretroviral therapy, viral "sanctuaries" persisted, with the highest levels of viral DNA and RNA found in the spleen, lymph nodes and gastrointestinal tract (North TW, Higgins J, Deere JD, et al. J Virol. 2010 Mar;84(6):2913-2922. Epub 2009 Dec 23).
For eradicating latent integrated HIV, he says the "shock and kill" strategy involves activating the virus and then stimulating it, leading to cell death (Hamer DH. Curr HIV Res. 2004 Apr;2(2):99-111). "The challenges are, how do we specifically kill the cells that are latently infected and deliver the drugs or deadly punch to initiate the cell apoptosis?" Dr. Schinazi says. Other potential approaches involve using anti-TNF-alpha treatment. "That will also be tested in the animal system we have developed."
In combating HCV, Dr. Schinazi says researchers have an advantage, because this virus does not establish latency. "Theoretically, we can eradicate this virus much more easily than HIV." Here, a promising drug candidate under development is a nucleoside developed at Emory in conjunction with Pharmasset, called R7128 (Roche). "The advantage of this nucleoside is that even when there is resistant virus, it is still active," he says.
In clinical testing, investigators combined R7128 (500 mg to 1,500 mg daily) with IFN and ribavirin for 28 days. "Preliminary results showed we had 85 percent rapid virological response in four weeks," Dr. Schinazi says. Researchers then combined the drug in doses of 500 mg or 1,000 mg daily with a PI (R7227, Roche; 100 mg or 200 mg daily) in an attempt to develop an IFN/ribavirin-free regimen.
"By day 14 there was a nearly five log10 drop irrespective of the dose (Gane EJ, Stedman C. First-in-man demonstration of potent antiviral activity with a nucleoside polymerase (R7128) and protease (R7227/ITMN-191) inhibitor combination in HCV: Safety, pharmacokinetics, and virologic results from INFORM-1 [abstract]. J Hepatol. 2008;50 (Suppl. 1): Abstract 1046, S380). Unfortunately, the PI caused some toxicity, so the dose has now been reduced to 100 mg daily, with a protease booster, a bit like we do with HIV," Dr. Schinazi says.
"This is where the future lies — the INFORM study demonstrated that two compounds with different targets can achieve tremendous viral reduction," he says. With HCV, "Cures are already possible with IFN and ribavirin. We just need to improve the SVR." He predicts that in the next year or so, drug combinations will provide SVR for more than 90 percent of patients with HCV.
Disclosures: Dr. Schinazi is founder and major shareholder of Pharmasset, Idenix and RFS Pharma. He also receives royalties from 3TC and LdT.
Source
How blocking the 'Programmed Death 1' protein may treat or prevent sepsis and severe infection
Public release date: 2-Aug-2010
Contact: Cody Mooneyhan
cmooneyhan@faseb.org
301-515-0371
Federation of American Societies for Experimental Biology
New research published in the Journal of Leukocyte Biology suggests that blocking a membrane protein called Programmed Death 1 improves survival in a clinically relevant model of severe infection
Scientists have made an important discovery that could lead to new drugs that reduce the severity of blood infections leading to sepsis. Research presented in the August 2010 issue of Journal of Leukocyte Biology (http://www.jleukbio.org) shows how interfering with the function of the cell membrane protein called "Programmed Death 1" (PD-1) improves survival in a clinically relevant model of severe infection.
"Clinical trials of anti-PD-1 are currently underway in patients with cancer and in patients with hepatitis C," said Richard S. Hotchkiss, M.D., co-study author from the Department of Anesthesiology at Washington University School of Medicine in St. Louis, MO. "It is hoped that blocking PD-1 will lead to enhanced immune function and a resultant improved tumor elimination and viral eradication respectively."
To make this discovery, the researchers studied two groups of mice with a surgically induced severe infection that simulates a ruptured appendix in humans. One group of mice received an inactive antibody while the other group of mice received an antibody that blocked PD-1. The mice that received the PD-1 blocking antibody had a greater survival rate when compared to the mice that received the inactive control antibody. Results show that PD-1 inhibits the ability of the immune system to fight infection by suppressing the function of immune cells. Thus, blocking PD-1 can restore the ability of the host to combat infections, also helping to improve chances for survival.
"This research may lead to a new class of drugs that could treat severe bacterial infections, including those that are becoming increasingly resistant to today's antibiotics," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, "This study is one of science's many steps to keep pace or a step ahead of the evolutionary progress that these microrganisms are making."
###
The Journal of Leukocyte Biology (http://www.jleukbio.org/) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
Details: Pavan Brahmamdam, Shigeaki Inoue, Jacqueline Unsinger, Katherine C. Chang, Jonathan E. McDunn, and Richard S. Hotchkiss Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol 2010 88: 233-240. doi: 10.1189/jlb.0110037 ; http://www.jleukbio.org/cgi/content/abstract/88/2/233
Source
Contact: Cody Mooneyhan
cmooneyhan@faseb.org
301-515-0371
Federation of American Societies for Experimental Biology
New research published in the Journal of Leukocyte Biology suggests that blocking a membrane protein called Programmed Death 1 improves survival in a clinically relevant model of severe infection
Scientists have made an important discovery that could lead to new drugs that reduce the severity of blood infections leading to sepsis. Research presented in the August 2010 issue of Journal of Leukocyte Biology (http://www.jleukbio.org) shows how interfering with the function of the cell membrane protein called "Programmed Death 1" (PD-1) improves survival in a clinically relevant model of severe infection.
"Clinical trials of anti-PD-1 are currently underway in patients with cancer and in patients with hepatitis C," said Richard S. Hotchkiss, M.D., co-study author from the Department of Anesthesiology at Washington University School of Medicine in St. Louis, MO. "It is hoped that blocking PD-1 will lead to enhanced immune function and a resultant improved tumor elimination and viral eradication respectively."
To make this discovery, the researchers studied two groups of mice with a surgically induced severe infection that simulates a ruptured appendix in humans. One group of mice received an inactive antibody while the other group of mice received an antibody that blocked PD-1. The mice that received the PD-1 blocking antibody had a greater survival rate when compared to the mice that received the inactive control antibody. Results show that PD-1 inhibits the ability of the immune system to fight infection by suppressing the function of immune cells. Thus, blocking PD-1 can restore the ability of the host to combat infections, also helping to improve chances for survival.
"This research may lead to a new class of drugs that could treat severe bacterial infections, including those that are becoming increasingly resistant to today's antibiotics," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, "This study is one of science's many steps to keep pace or a step ahead of the evolutionary progress that these microrganisms are making."
###
The Journal of Leukocyte Biology (http://www.jleukbio.org/) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
Details: Pavan Brahmamdam, Shigeaki Inoue, Jacqueline Unsinger, Katherine C. Chang, Jonathan E. McDunn, and Richard S. Hotchkiss Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol 2010 88: 233-240. doi: 10.1189/jlb.0110037 ; http://www.jleukbio.org/cgi/content/abstract/88/2/233
Source
New York To Reduce The Spread Of HIV And AIDS
Source: Governor of New York
Posted on: 2nd August 2010
Governor David A. Paterson has announced the enactment of two bills to reduce the spread of HIV/AIDS by updating New York’s HIV testing law to encourage increased testing rates and remove disincentives to participation in needle exchange and syringe access programs.
The Governor signed into law S.8227/A.11487, which will allow patients to agree to HIV testing as part of a general signed consent to medical care that remains in effect until it is revoked or expires.
The bill will also require health care providers to offer testing to their patients between 13 and 64 years of age, as recommended by the federal Centers for Disease and Control (CDC), and will facilitate authorization for testing in the case of certain occupational exposures to HIV infection.
“The enactment of this bill represents a significant step forward in combating the HIV/AIDS epidemic,” Governor Paterson said. “By making HIV testing a routine part of health care, this legislation will increase HIV testing rates, letting people learn their status and begin treatment at an earlier stage, which can significantly improve the length and quality of life and help reduce transmission of the disease.”
The bill will also, among other things:
These public health programs that provide intravenous drug users with access to clean syringes and to substance abuse counseling and health care have operated in New York for many years. Numerous State, national and international studies have found that such programs are very effective in reducing transmission of blood-borne diseases such as HIV and Hepatitis C.
A number of participants in such programs have been arrested for possession of needles and syringes which, although permitted under the Public Health Law, is not reflected in the Penal Law where the crimes are defined.
In addition, residue in such syringes could subject someone to criminal charges under the Penal Law, which is clearly in conflict with the spirit of the Public Health Law provisions and the objectives of the needle exchange and syringe access programs.
“The success of needle exchange and syringe access programs has been repeatedly verified to be instrumental in reducing the transmission of blood-borne diseases,” Governor Paterson said. “I proposed this legislation to prevent people from being arrested unnecessarily, thus ensuring that syringe users are not deterred from participating in these important programs.”
The Governor’s Program Bill No. 23 will:
Posted on: 2nd August 2010
Governor David A. Paterson has announced the enactment of two bills to reduce the spread of HIV/AIDS by updating New York’s HIV testing law to encourage increased testing rates and remove disincentives to participation in needle exchange and syringe access programs.
The Governor signed into law S.8227/A.11487, which will allow patients to agree to HIV testing as part of a general signed consent to medical care that remains in effect until it is revoked or expires.
The bill will also require health care providers to offer testing to their patients between 13 and 64 years of age, as recommended by the federal Centers for Disease and Control (CDC), and will facilitate authorization for testing in the case of certain occupational exposures to HIV infection.
“The enactment of this bill represents a significant step forward in combating the HIV/AIDS epidemic,” Governor Paterson said. “By making HIV testing a routine part of health care, this legislation will increase HIV testing rates, letting people learn their status and begin treatment at an earlier stage, which can significantly improve the length and quality of life and help reduce transmission of the disease.”
The bill will also, among other things:
- Allow oral consent to an HIV test for a “rapid HIV test,” a newer type of testing that is generally available in settings that include hospitals and clinics;
- Require, in accordance with the CDC’s 2006 recommendations, that an HIV related test be offered to every individual between the ages of 13 and 64 years of age receiving health services in any health setting, including hospitals, emergency rooms, hospital outpatient departments, and primary care settings including physician, physician assistant, nurse practitioner and midwife offices;
- Permit anonymous testing of the blood of a person who is deceased, comatose or otherwise lacks the ability to consent, if someone such as a health care worker is exposed to the person’s blood and no one with the authority to consent to testing can be found in time for the exposed worker to begin medical treatment for HIV.
These public health programs that provide intravenous drug users with access to clean syringes and to substance abuse counseling and health care have operated in New York for many years. Numerous State, national and international studies have found that such programs are very effective in reducing transmission of blood-borne diseases such as HIV and Hepatitis C.
A number of participants in such programs have been arrested for possession of needles and syringes which, although permitted under the Public Health Law, is not reflected in the Penal Law where the crimes are defined.
In addition, residue in such syringes could subject someone to criminal charges under the Penal Law, which is clearly in conflict with the spirit of the Public Health Law provisions and the objectives of the needle exchange and syringe access programs.
“The success of needle exchange and syringe access programs has been repeatedly verified to be instrumental in reducing the transmission of blood-borne diseases,” Governor Paterson said. “I proposed this legislation to prevent people from being arrested unnecessarily, thus ensuring that syringe users are not deterred from participating in these important programs.”
The Governor’s Program Bill No. 23 will:
- Clarify in the Penal Law that a person does not act unlawfully by possessing a hypodermic needle or syringe if he or she participates in a needle exchange or syringe access program authorized under the Public Health Law;
- Provide that possession of a residual amount of a controlled substance on a needle or syringe does not constitute a criminal act if the individual is permitted to possess such needle or syringe under the Public Health Law; and
- Require the Division of Criminal Justice Services to periodically notify law enforcement agencies and prosecutors about the right of individuals to possess syringes under a qualifying public health program and how to verify that a person is participating in such a program.
August 1, 2010
Statement from Assistant Secretary for Health, Dr. Howard Koh, Regarding National Minority Donor Awareness Day
FOR IMMEDIATE RELEASE
Friday, July 30, 2010
Contact: HHS Press Office
(202) 690-6343
August 1, is National Minority Donor Awareness Day, an opportunity to honor minority organ donors and their families, encourage greater donor enrollment among all racial and ethnic groups, and promote healthy living to decrease the need for organ transplantation.
At no time has the need for organ donations been greater: today, more than 108,000 Americans are waiting for an organ transplant. Of these, 55 percent are minorities. In 2009, minorities accounted for approximately 35 percent of organ and tissue donors in the country.
People of minority backgrounds have a particularly high need for organ transplants because some diseases that can lead to organ failure are found more frequently in such populations compared to others. For example, African Americans, Asian Americans and Pacific Islanders, and Hispanics are more likely than whites to suffer from end-stage renal (kidney) disease, often as a result of high blood pressure and other conditions that damage the kidneys. Native Americans are more likely than whites to suffer from diabetes.
Although organs are not matched according to ethnicity, and people of different ethnicities are often matched through donation, those on waiting lists have a better chance of being a recipient if large numbers of donors are available from their ethnic background. This reflects the higher likelihood of compatible blood type and tissue markers – critical for donor/recipient matching – among members of the same ethnicity. Hence, greater diversity of donors may potentially increase access to transplantation for all patients on the waiting list.
To become part of the movement:
--Enroll in your state donor registry. Learn how at: www.organdonor.gov/donor/registry.shtm.
--Designate your decision on your driver’s license. Do this when you obtain or renew your license.
Talk to your family now about your donation decision. Help your family understand your wish to be an organ and tissue donor before a crisis occurs. Then they will be prepared to serve as your advocate for donation.
We can celebrate many gifts in this world. Encourage your family and friends to choose organ donation and give the greatest gifts of all – hope and life.
Howard K. Koh, M.D., M.P.H.
Assistant Secretary for Health
###
Note: All HHS press releases, fact sheets and other press materials are available at http://www.hhs.gov/news.
Last revised: July 30, 2010
Source
Friday, July 30, 2010
Contact: HHS Press Office
(202) 690-6343
August 1, is National Minority Donor Awareness Day, an opportunity to honor minority organ donors and their families, encourage greater donor enrollment among all racial and ethnic groups, and promote healthy living to decrease the need for organ transplantation.
At no time has the need for organ donations been greater: today, more than 108,000 Americans are waiting for an organ transplant. Of these, 55 percent are minorities. In 2009, minorities accounted for approximately 35 percent of organ and tissue donors in the country.
People of minority backgrounds have a particularly high need for organ transplants because some diseases that can lead to organ failure are found more frequently in such populations compared to others. For example, African Americans, Asian Americans and Pacific Islanders, and Hispanics are more likely than whites to suffer from end-stage renal (kidney) disease, often as a result of high blood pressure and other conditions that damage the kidneys. Native Americans are more likely than whites to suffer from diabetes.
Although organs are not matched according to ethnicity, and people of different ethnicities are often matched through donation, those on waiting lists have a better chance of being a recipient if large numbers of donors are available from their ethnic background. This reflects the higher likelihood of compatible blood type and tissue markers – critical for donor/recipient matching – among members of the same ethnicity. Hence, greater diversity of donors may potentially increase access to transplantation for all patients on the waiting list.
To become part of the movement:
--Enroll in your state donor registry. Learn how at: www.organdonor.gov/donor/registry.shtm.
--Designate your decision on your driver’s license. Do this when you obtain or renew your license.
Talk to your family now about your donation decision. Help your family understand your wish to be an organ and tissue donor before a crisis occurs. Then they will be prepared to serve as your advocate for donation.
We can celebrate many gifts in this world. Encourage your family and friends to choose organ donation and give the greatest gifts of all – hope and life.
Howard K. Koh, M.D., M.P.H.
Assistant Secretary for Health
###
Note: All HHS press releases, fact sheets and other press materials are available at http://www.hhs.gov/news.
Last revised: July 30, 2010
Source
New insights into how stem cells determine what tissue to become
August 1, 2010
Within 24 hours of culturing adult human stem cells on a new type of matrix, University of Michigan researchers were able to make predictions about how the cells would differentiate, or what type of tissue they would become. Their results are published in the Aug. 1 edition of Nature Methods.
Differentiation is the process of stem cells morphing into other types of cells. Understanding it is key to developing future stem cell-based regenerative therapies.
"We show, for the first time, that we can predict stem cell differentiation as early as Day 1," said Jianping Fu, an assistant professor in mechanical engineering and biomedical engineering who is the first author on the paper.
"Normally, it takes weeks or maybe longer to know how the stem cell will differentiate. Our work could speed up this lengthy process and could have important applications in drug screening and regenerative medicine. Our method could provide early indications of how the stem cells are differentiating and what the cell types they are becoming under a new drug treatment."
In this study, Fu and his colleagues examined stem cell mechanics, the slight forces the cells exert on the materials they are attached to. These traction forces were suspected to be involved in differentiation, but they have not been as widely studied as the chemical triggers. In this paper, the researchers show that the stiffness of the material on which stem cells are cultivated in a lab does, in fact, help to determine what type of cells they turn into.
"Our research confirms that mechanical factors are as important as the chemical factors regulating differentiation," Fu said. "The mechanical aspects have, until now, been largely ignored by stem cell biologists."
The researchers built a novel type of stem cell matrix, or scaffold, whose stiffness can be adjusted without altering its chemical composition, which cannot be done with conventional stem cell growth matrices, Fu said.
The new scaffold resembles an ultrafine carpet of "microposts," hair-like projections made of the elastic polymer polydimethylsiloxane---a key component in Silly Putty, Fu said. By adjusting the height of the microposts, the researchers were able to adjust the rigidity of the matrix.
In this experiment, the engineers used human mesenchymal stem cells, which are found in bone marrow and other connective tissues such as fat. The stem cells differentiated into bone when grown on stiffer scaffolds, and into fat when grown on more flexible scaffolds.
Once the researchers observed the cells differentiating according to the mechanical stiffness of the substrate, they decided to measure the cellular traction forces throughout the culturing process to see if they could predict how the cells would differentiate.
Using a technique called fluorescent microscopy, the researchers measured the bending of the microposts in order to quantify the traction forces.
"Our study shows that if the stem cells determine to differentiate into one cell type then their traction forces can be much greater than the ones that do not differentiate, or that differentiate into another cell type," Fu said. "We prove that we can use the evolution of the traction force as early indicators for stem cell differentiation."
The new matrix---manufactured through an inexpensive molding process---is so cheap to make that the researchers are giving it away to any interested scientists or engineers.
"We think this toolset provides a newly accessible, practical methodology for the whole community," Fu said.
More information: "Mechanical regulation of cell function using geometrically modulated elastomeric substrates," Nature Methods.
Provided by University of Michigan
Source
This is an immunofluorescence image of a human mesenchymal stem cell growing on a plate of microposts, which have the approximate consistency of Silly Putty. This image was taken after one day of culturing. The red dots are the microposts, which are relatively short in this sample. The green is the cell and the blue is its nucleus. This cell will differentiate into a bone cell. Credit: Michael T. Yang (University of Pennsylvania)
Within 24 hours of culturing adult human stem cells on a new type of matrix, University of Michigan researchers were able to make predictions about how the cells would differentiate, or what type of tissue they would become. Their results are published in the Aug. 1 edition of Nature Methods.
Differentiation is the process of stem cells morphing into other types of cells. Understanding it is key to developing future stem cell-based regenerative therapies.
"We show, for the first time, that we can predict stem cell differentiation as early as Day 1," said Jianping Fu, an assistant professor in mechanical engineering and biomedical engineering who is the first author on the paper.
"Normally, it takes weeks or maybe longer to know how the stem cell will differentiate. Our work could speed up this lengthy process and could have important applications in drug screening and regenerative medicine. Our method could provide early indications of how the stem cells are differentiating and what the cell types they are becoming under a new drug treatment."
In this study, Fu and his colleagues examined stem cell mechanics, the slight forces the cells exert on the materials they are attached to. These traction forces were suspected to be involved in differentiation, but they have not been as widely studied as the chemical triggers. In this paper, the researchers show that the stiffness of the material on which stem cells are cultivated in a lab does, in fact, help to determine what type of cells they turn into.
"Our research confirms that mechanical factors are as important as the chemical factors regulating differentiation," Fu said. "The mechanical aspects have, until now, been largely ignored by stem cell biologists."
The researchers built a novel type of stem cell matrix, or scaffold, whose stiffness can be adjusted without altering its chemical composition, which cannot be done with conventional stem cell growth matrices, Fu said.
This is an image taken with a scanning electron microscope of a human mesenchymal stem cell growing on a plate of long microposts approximately 13 microns in length. After one day of culturing, this cell exerts centripetal force, which can be seen in the bending of the microposts. This cell will differentiate into a fat cell. Credit: Jianping Fu (University of Michigan)
The new scaffold resembles an ultrafine carpet of "microposts," hair-like projections made of the elastic polymer polydimethylsiloxane---a key component in Silly Putty, Fu said. By adjusting the height of the microposts, the researchers were able to adjust the rigidity of the matrix.
In this experiment, the engineers used human mesenchymal stem cells, which are found in bone marrow and other connective tissues such as fat. The stem cells differentiated into bone when grown on stiffer scaffolds, and into fat when grown on more flexible scaffolds.
Once the researchers observed the cells differentiating according to the mechanical stiffness of the substrate, they decided to measure the cellular traction forces throughout the culturing process to see if they could predict how the cells would differentiate.
Using a technique called fluorescent microscopy, the researchers measured the bending of the microposts in order to quantify the traction forces.
This is an image taken with a scanning electron microscope of human mesenchymal stem cells growing on a plate of short microposts. After one day of culturing, these cells spread more than cells cultured on long microposts. These will differentiate into bone cells. Even though these cells bend their shorter microposts less than their counterparts growing on longer microposts, they exert greater force to do so. Credit: Jianping Fu (University of Michigan)
"Our study shows that if the stem cells determine to differentiate into one cell type then their traction forces can be much greater than the ones that do not differentiate, or that differentiate into another cell type," Fu said. "We prove that we can use the evolution of the traction force as early indicators for stem cell differentiation."
The new matrix---manufactured through an inexpensive molding process---is so cheap to make that the researchers are giving it away to any interested scientists or engineers.
"We think this toolset provides a newly accessible, practical methodology for the whole community," Fu said.
More information: "Mechanical regulation of cell function using geometrically modulated elastomeric substrates," Nature Methods.
Provided by University of Michigan
Source
EASL Publishes European Clinical Practice Guidelines For The Management Of Ascites, SBP, And Hepatorenal Syndrome In Cirrhosis
Article Date: 01 Aug 2010 - 0:00 PDT
The European Association for the Study of the Liver (EASL) - the leading European scientific society dedicated to promoting research and education in hepatology - publishes clinical practice guidelines for the management of ascites, the most common complication of cirrhosis. The peer reviewed guidelines will be available in the September 2010 issue, (Volume 53, No.3) of the Journal of Hepatology and online in advance of publication here. They also provide recommendations for the management of spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome, which often affect patients with cirrhosis[1].
An estimated 75 percent of patients presenting with ascites in Western Europe and the USA have cirrhosis as the underlying cause. The development of ascites is an extremely common yet debilitating complication for cirrhotic patients and has a huge impact on their life expectancy and quality of life. SBP and hepatorenal syndrome are ominous complications of which patients with ascites are at risk. They carry a high mortality and prophylactic measures, early diagnosis and appropriate treatments are crucial, especially to bridge eligible patients to liver transplantation.
"It is estimated that almost 60 percent of cirrhotic patients develop ascites within 10 years of their disease, which is a huge proportion of patients. These guidelines provide clinicians with the latest recommendations from a panel of experts on the management of ascites, SBP and hepatorenal syndrome. It is hoped that the guidelines will improve and facilitate best practice and ultimately improve disease outcomes and symptoms for cirrhotic patients in the future," stated Pere Ginès, lead contributor of the guidelines.
These guidelines aim to assist clinicians in the decision making and management process for ascites, SBP and hepatorenal syndrome, as well as inform patients and their carers of optimal treatment and care. New and updated best practice for the screening, diagnosis and management of these conditions are offered, with particular emphasis on:
-- Prevalence and prognosis of ascites
-- Management of the various stages of its development
-- Diagnostic strategies for ascites, SBP and hepatorenal syndrome
-- The use of drugs, antibiotics and diuretics and their associated complications
-- Ascitic fluid analysis for assessing peritoneal infections
-- Methods to improve renal function and considerations of liver transplantation
"EASL is dedicated to promoting research and education in the field of hepatology to improve the treatment of liver disease throughout the world. Its series of clinical practice guidelines aims to promote best practise to drive better clinical outcomes and inform both the scientific community and the wider public of the latest developments in the field. We hope these new ascites guidelines provide clinicians with the most up-to-date, evidence based methods for the management of patients affected by this common and debilitating disease" added Professor Heiner Wedemeyer, EASL Secretary General.
[1] Cirrhosis is associated with portal hypertension which increases pressure in the portal venous system and forces fluid into the abdominal cavity (ascites). This leads to fluid retention in the kidneys and decreased renal perfusion, which can eventually progress to hepatorenal syndrome. Another possible complication is spontaneous bacterial peritonitis, an acute bacterial infection of ascitic fluid.
Source:
European Association for the Study of the Liver
Source
The European Association for the Study of the Liver (EASL) - the leading European scientific society dedicated to promoting research and education in hepatology - publishes clinical practice guidelines for the management of ascites, the most common complication of cirrhosis. The peer reviewed guidelines will be available in the September 2010 issue, (Volume 53, No.3) of the Journal of Hepatology and online in advance of publication here. They also provide recommendations for the management of spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome, which often affect patients with cirrhosis[1].
An estimated 75 percent of patients presenting with ascites in Western Europe and the USA have cirrhosis as the underlying cause. The development of ascites is an extremely common yet debilitating complication for cirrhotic patients and has a huge impact on their life expectancy and quality of life. SBP and hepatorenal syndrome are ominous complications of which patients with ascites are at risk. They carry a high mortality and prophylactic measures, early diagnosis and appropriate treatments are crucial, especially to bridge eligible patients to liver transplantation.
"It is estimated that almost 60 percent of cirrhotic patients develop ascites within 10 years of their disease, which is a huge proportion of patients. These guidelines provide clinicians with the latest recommendations from a panel of experts on the management of ascites, SBP and hepatorenal syndrome. It is hoped that the guidelines will improve and facilitate best practice and ultimately improve disease outcomes and symptoms for cirrhotic patients in the future," stated Pere Ginès, lead contributor of the guidelines.
These guidelines aim to assist clinicians in the decision making and management process for ascites, SBP and hepatorenal syndrome, as well as inform patients and their carers of optimal treatment and care. New and updated best practice for the screening, diagnosis and management of these conditions are offered, with particular emphasis on:
-- Prevalence and prognosis of ascites
-- Management of the various stages of its development
-- Diagnostic strategies for ascites, SBP and hepatorenal syndrome
-- The use of drugs, antibiotics and diuretics and their associated complications
-- Ascitic fluid analysis for assessing peritoneal infections
-- Methods to improve renal function and considerations of liver transplantation
"EASL is dedicated to promoting research and education in the field of hepatology to improve the treatment of liver disease throughout the world. Its series of clinical practice guidelines aims to promote best practise to drive better clinical outcomes and inform both the scientific community and the wider public of the latest developments in the field. We hope these new ascites guidelines provide clinicians with the most up-to-date, evidence based methods for the management of patients affected by this common and debilitating disease" added Professor Heiner Wedemeyer, EASL Secretary General.
[1] Cirrhosis is associated with portal hypertension which increases pressure in the portal venous system and forces fluid into the abdominal cavity (ascites). This leads to fluid retention in the kidneys and decreased renal perfusion, which can eventually progress to hepatorenal syndrome. Another possible complication is spontaneous bacterial peritonitis, an acute bacterial infection of ascitic fluid.
Source:
European Association for the Study of the Liver
Source
Virologic response rates of weight-based taribavirin versus ribavirin in naïve chronic hepatitis C genotype 1 patients
Hepatology
Volume 9999 Issue 999A, Page NA
Published Online: 30 Jun 2010
Copyright © 2010 American Association for the Study of Liver Diseases
F Poordad 1 *, E Lawitz 2, ML Shiffman 3, T Hassanein 4, AJ Muir 5, B Bacon 6, J Heise 7, D Halliman 7, E Chun 7, J Hammond 7
1 Cedars-Sinai Medical Center, Los Angeles, CA, USA
2 Alamo Medical Research, San Antonio, TX, USA
3 McGuire Research Institute, McGuire Veterans Administration Medical Center, Richmond, VA, USA
4 Southern California Liver Centers, San Clemente, CA, USA
5 Duke Clinical Research Institute, Duke University, Durham, NC, USA
6 Saint Louis University School of Medicine, St. Louis, MO, USA
7 Valeant Pharmaceuticals North America, Aliso Viejo, CA, USA
email: F Poordad (fred.poordad@cshs.org)
*Correspondence to F Poordad, Cedars -Sinai Medical Center, Hepatology and Liver Transplantation, Los Angeles, California, United States
Keywords
anemia • erythropoiesis-stimulating agents • weight-based dosing • antiviral dosing • clinical trial
Abstract
BACKGROUND:
Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of chronic hepatitis C patients.
The study aimed to determine if weight-based dosing (WBD) of taribavirin (TBV), an oral pro-drug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration.
METHODS:
A US phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naïve, genotype 1 patients stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800 -1400 mg/day) with pegylated interferon alfa-2b for 48 weeks.
RESULTS:
The SVR rates in this difficult to cure patient demographics (mean age 49 yrs; 61% male; 30% African-American or Latino; high viral load; advanced fibrosis; and mean weight 82 kg) were 28.4%, 24.3%, 20.6% and 21.4% in the 20, 25, 30 mg/kg TBV groups and RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (p<0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7% respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting.
CONCLUSIONS:
All TBV doses demonstrated efficacy and tolerability comparable to that of RBV, however the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV 20-25 mg/kg than RBV. These data suggest WBD with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. (HEPATOLOGY 2010.)
Received: 24 April 2010; Revised: 18 June 2010; Accepted: 22 June 2010
Digital Object Identifier (DOI)
10.1002/hep.23827 About DOI
Source
Volume 9999 Issue 999A, Page NA
Published Online: 30 Jun 2010
Copyright © 2010 American Association for the Study of Liver Diseases
F Poordad 1 *, E Lawitz 2, ML Shiffman 3, T Hassanein 4, AJ Muir 5, B Bacon 6, J Heise 7, D Halliman 7, E Chun 7, J Hammond 7
1 Cedars-Sinai Medical Center, Los Angeles, CA, USA
2 Alamo Medical Research, San Antonio, TX, USA
3 McGuire Research Institute, McGuire Veterans Administration Medical Center, Richmond, VA, USA
4 Southern California Liver Centers, San Clemente, CA, USA
5 Duke Clinical Research Institute, Duke University, Durham, NC, USA
6 Saint Louis University School of Medicine, St. Louis, MO, USA
7 Valeant Pharmaceuticals North America, Aliso Viejo, CA, USA
email: F Poordad (fred.poordad@cshs.org)
*Correspondence to F Poordad, Cedars -Sinai Medical Center, Hepatology and Liver Transplantation, Los Angeles, California, United States
Keywords
anemia • erythropoiesis-stimulating agents • weight-based dosing • antiviral dosing • clinical trial
Abstract
BACKGROUND:
Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of chronic hepatitis C patients.
The study aimed to determine if weight-based dosing (WBD) of taribavirin (TBV), an oral pro-drug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration.
METHODS:
A US phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naïve, genotype 1 patients stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800 -1400 mg/day) with pegylated interferon alfa-2b for 48 weeks.
RESULTS:
The SVR rates in this difficult to cure patient demographics (mean age 49 yrs; 61% male; 30% African-American or Latino; high viral load; advanced fibrosis; and mean weight 82 kg) were 28.4%, 24.3%, 20.6% and 21.4% in the 20, 25, 30 mg/kg TBV groups and RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (p<0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7% respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting.
CONCLUSIONS:
All TBV doses demonstrated efficacy and tolerability comparable to that of RBV, however the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV 20-25 mg/kg than RBV. These data suggest WBD with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. (HEPATOLOGY 2010.)
Received: 24 April 2010; Revised: 18 June 2010; Accepted: 22 June 2010
Digital Object Identifier (DOI)
10.1002/hep.23827 About DOI
Source
Retransplantation in patients with hepatitis C recurrence after liver transplantation
José A. Carrión, Miquel Navasa, Xavier Forns
Received 10 November 2009; received in revised form 8 June 2010; accepted 10 June 2010. published online 30 July 2010.
Uncorrected Proof
HCV-infection recurs universally after liver transplantation (LT) and fibrosis progression is accelerated in the graft. Retransplantation (RT) is the only therapeutic option to achieve long-term survival in patients with decompensated cirrhosis after LT. Patient and graft survival rates after RT are inferior to those after primary LT. It is generally accepted that severe hepatitis C recurrence (cholestatic hepatitis) and forms with rapid fibrosis progression have a poor survival after RT. However, it is not clear whether rapid fibrosis progression in the first graft will be followed by the same rate of fibrosis progression in the second graft. The use of prognostic scores as screening tools has shown an improvement in survival in HCV-infected patients after RT, reaching similar survival rates as those obtained in non HCV-infected patients. Moreover, these scores can identify candidates with a high risk of mortality in whom the use of a new organ would be unreasonable. Prevention of severe hepatitis C recurrence could be the first step to avoid RT. Thus, antiviral treatment on the waiting list (if possible) and early identification and treatment of patients with severe hepatitis C recurrence may be a good strategy to avoid RT. In addition, active management of factors which can accelerate fibrosis progression (donor age, post-transplant diabetes, high dose of corticosteroids) might reduce the incidence of severe forms of hepatitis C recurrence.
Abbreviations: RT, retransplantation, LT, liver transplantation, HCV, hepatitis C virus, PNF, primary non-function, HAT, hepatic artery thrombosis, UNOS, United Network for Organ Sharing, MELD, model for end-stage liver disease, ECD, extender criteria donors, HCC, hepatocellular carcinoma, SVR, sustained virological response
Keywords: Severe recurrence, Cirrhosis, MELD, Survival
Liver Unit, Institut de Malalties Digestives, Hospital ClÃnic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
Corresponding author. Address: Liver Unit, Escala 7, 3 pis., Villarroel 170, Hospital Clinic, Barcelona 08036, Spain. Tel.: +34 93 227 54 99; fax: +34 93 451 55 22.
PII: S0168-8278(10)00623-9
doi:10.1016/j.jhep.2010.06.006
© 2010 Published by Elsevier Inc.
Source
Received 10 November 2009; received in revised form 8 June 2010; accepted 10 June 2010. published online 30 July 2010.
Uncorrected Proof
HCV-infection recurs universally after liver transplantation (LT) and fibrosis progression is accelerated in the graft. Retransplantation (RT) is the only therapeutic option to achieve long-term survival in patients with decompensated cirrhosis after LT. Patient and graft survival rates after RT are inferior to those after primary LT. It is generally accepted that severe hepatitis C recurrence (cholestatic hepatitis) and forms with rapid fibrosis progression have a poor survival after RT. However, it is not clear whether rapid fibrosis progression in the first graft will be followed by the same rate of fibrosis progression in the second graft. The use of prognostic scores as screening tools has shown an improvement in survival in HCV-infected patients after RT, reaching similar survival rates as those obtained in non HCV-infected patients. Moreover, these scores can identify candidates with a high risk of mortality in whom the use of a new organ would be unreasonable. Prevention of severe hepatitis C recurrence could be the first step to avoid RT. Thus, antiviral treatment on the waiting list (if possible) and early identification and treatment of patients with severe hepatitis C recurrence may be a good strategy to avoid RT. In addition, active management of factors which can accelerate fibrosis progression (donor age, post-transplant diabetes, high dose of corticosteroids) might reduce the incidence of severe forms of hepatitis C recurrence.
Abbreviations: RT, retransplantation, LT, liver transplantation, HCV, hepatitis C virus, PNF, primary non-function, HAT, hepatic artery thrombosis, UNOS, United Network for Organ Sharing, MELD, model for end-stage liver disease, ECD, extender criteria donors, HCC, hepatocellular carcinoma, SVR, sustained virological response
Keywords: Severe recurrence, Cirrhosis, MELD, Survival
Liver Unit, Institut de Malalties Digestives, Hospital ClÃnic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
Corresponding author. Address: Liver Unit, Escala 7, 3 pis., Villarroel 170, Hospital Clinic, Barcelona 08036, Spain. Tel.: +34 93 227 54 99; fax: +34 93 451 55 22.
PII: S0168-8278(10)00623-9
doi:10.1016/j.jhep.2010.06.006
© 2010 Published by Elsevier Inc.
Source
Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease
Gastroenterology
Volume 139, Issue 2 , Pages 456-463, August 2010
Jody Dushay, Patricia C. Chui, Gosala S. Gopalakrishnan, Marta Varela–Rey, Meghan Crawley, Ffolliott M. Fisher, Michael K. Badman, Maria L. Martinez–Chantar, Eleftheria Maratos–Flier
Received 21 January 2010; accepted 29 April 2010. published online 07 May 2010.
Abstract
Background & Aims
Fibroblast growth factor 21 (FGF21) is an hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index (BMI), but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver messenger RNA (mRNA) expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
Methods
Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH.
Results
There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A nonstatistically significant fall in FGF21 levels was seen after a 72-hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased.
Conclusions
FGF21 correlates with BMI and may be a novel biomarker for NAFLD, but is not nutritionally regulated in humans.
Keywords: FGF21, NAFLD, NASH, Obesity
Abbreviations used in this paper: BMI, body mass index, FGF21, fibroblast growth factor 21, GCRC, General Clinical Research Center, KD, ketogenic diet, mRNA, messenger RNA, NAFLD, nonalcoholic fatty liver disease, NASH, nonalcoholic steatohepatitis, PPARα, peroxisome proliferator−activated receptor-α
Conflicts of interest The authors disclose no conflicts.
Funding This study was supported in part by National Institutes of Health (NIH) grant M01-RR01032, Beth Israel Deaconess Medical Center General Clinical Research Center, NIH grant AT-1576, SAF2005-00855, and HEPADIP-EULSHM-CT-205 (to M.L.M.-C.), NIH grants 5R01DK069983-04 and NIH/5P01DK056106-10 (to E.M.F.), and the Boston Obesity and Nutrition Research Center DK46200.
PII: S0016-5085(10)00662-1
doi:10.1053/j.gastro.2010.04.054
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Volume 139, Issue 2 , Pages 456-463, August 2010
Jody Dushay, Patricia C. Chui, Gosala S. Gopalakrishnan, Marta Varela–Rey, Meghan Crawley, Ffolliott M. Fisher, Michael K. Badman, Maria L. Martinez–Chantar, Eleftheria Maratos–Flier
Received 21 January 2010; accepted 29 April 2010. published online 07 May 2010.
Abstract
Background & Aims
Fibroblast growth factor 21 (FGF21) is an hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index (BMI), but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver messenger RNA (mRNA) expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
Methods
Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH.
Results
There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A nonstatistically significant fall in FGF21 levels was seen after a 72-hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased.
Conclusions
FGF21 correlates with BMI and may be a novel biomarker for NAFLD, but is not nutritionally regulated in humans.
Keywords: FGF21, NAFLD, NASH, Obesity
Abbreviations used in this paper: BMI, body mass index, FGF21, fibroblast growth factor 21, GCRC, General Clinical Research Center, KD, ketogenic diet, mRNA, messenger RNA, NAFLD, nonalcoholic fatty liver disease, NASH, nonalcoholic steatohepatitis, PPARα, peroxisome proliferator−activated receptor-α
Conflicts of interest The authors disclose no conflicts.
Funding This study was supported in part by National Institutes of Health (NIH) grant M01-RR01032, Beth Israel Deaconess Medical Center General Clinical Research Center, NIH grant AT-1576, SAF2005-00855, and HEPADIP-EULSHM-CT-205 (to M.L.M.-C.), NIH grants 5R01DK069983-04 and NIH/5P01DK056106-10 (to E.M.F.), and the Boston Obesity and Nutrition Research Center DK46200.
PII: S0016-5085(10)00662-1
doi:10.1053/j.gastro.2010.04.054
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Eating Spicy Curry food could Reduce Liver Damage
A chief constituent of the Indian spice turmeric was found to reduce the inflammation and fibrosis (Development of excess fibrous tissue in an organ) in an animal study. Research work in rodents with chemically induced liver injury found that curcumin, a chemical in turmeric which is responsible for giving curry a yellow colour, has anti-inflammatory and anti-oxidative activities. The compound has been used since years in Ayurvedic medical specialty to treat a various gastrointestinal problems. However, latest research indicates that the compound may have other therapeutic applications, with potential effects on liver disorders. The new study proposed that that mice fed with curcumin had very less liver damage than other group which was on a normal diet.
The investigators in this study have looked into how curcumin saved mice that had been grew for inflammation in their bile ducts and liver injury. The study was aimed for screening out of mice model for a group of disease known as cholangiopathy. It is caused by inflammatory process and fibrosis of bile duct in liver which may cause blockage of bile flow to gut and may result in to jaundice, liver failure, liver cancer or other injuries to liver. The mice used in the study were bred to have a type of chronic cholangiopathy. The investigators did screening of various liver function tests for finding any sign of liver injury before and after the mice were fed with curcumin.
The results of this study indicated that liver injury, jaundice and scarring (which may lead to fibrosis) are reduced by the curcumin intake. The results also showed that curcumin may work on multiple targets in liver and thereby regulating numerous cellular events in mice. The underlying cellular process that is affected be curcumin rich diet might turn out to be promising targets for developing new drugs. As the efficacy of available medical alternatives to slow the progression of liver diseases is very narrow, there is a requirement for new and effectual medical intervention strategy. The finding of this study has opened the doors for newer treatment option for liver damage.
On the other hand, the hypothesis is in its early stage and it will be too early to say that the new treatment option might develop from this spice. There is no proposal from the study that consumption of turmeric will comprise the similar result or be a helpful treatment for human being. Nevertheless, researchers are taking this finding in positive ways and have started working in this direction.
Source
Ablate and Wait in Liver CA, Experts Suggest
By Charles Bankhead, Staff Writer, MedPage Today
Published: July 30, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Outcomes in all patients with hepatocellular carcinoma might improve with an "ablate- and-wait" strategy versus rapid transplantation, according to a group of clinicians who have regularly used the strategy.
Use of radiofrequency ablation and chemoembolization to downstage large tumors has shown that about 30% of patients do not qualify for transplantation because of disease progression. The strategy warrants consideration for all patients with hepatocellular carcinoma, regardless of whether they fall within the Milan criteria, according to authors of an article in the August issue of Liver Transplantation.
"Those patients who make it to transplantation have an excellent outcome as compared to patients transplanted with tumors beyond the Milan criteria who are not treated," John Roberts, MD, of the University of California San Francisco, and colleagues wrote in an opinion piece.
"The median time between the first ablative procedure and transplantation was 8.2 months with a range of 3 to 25 months. This approach suggests that the test of time may be the surest method to select patients with hepatocellular carcinoma who are destined to have good transplant outcomes."
The authors argue that their approach of ablating the tumor and then waiting to see whether it recurs or progresses should be expanded to all patients listed for transplantation because of hepatocellular carcinoma. Treating and waiting could help reduce the use of scarce donor organs in patients who will have recurrent disease.
"Our experience with ablative treatment and then observation suggests that the ultimate outcomes of transplantation are not dependent on the primary tumor but more on time spent waiting for transplantation," the authors wrote in their conclusion. "It would seem logical that smaller and/or fewer tumors, though more unlikely to have spread, would also benefit from a period of time if the primary tumor can be controlled."
"The waiting period may be able to decrease the 10% recurrence rate seen in patients transplanted within Milan," they added.
Published more than a decade ago, the Milan criteria for liver transplantation in patients with hepatocellular carcinoma won support because they seemed to identify patients likely to have good transplantation outcomes (N Engl J Med 1996; 334: 693-699). Based on tumor size and number, the criteria fell victim to the same fallacy as other criteria have, according to the authors.
"It has not been shown that there is any particular tumor size that represents no risk of recurrence, at least among those tumors that can be detected radiologically," Roberts and co-authors wrote in their introduction. "Furthermore, the degree of risk is not the same for all patients within the Milan criteria."
The San Francisco group's experience with a strategy of ablate and wait has indicated that patients who fall far outside the Milan criteria do quite well after transplantation, if time is added as a criterion for transplantation. A report covering their experience with 61 patients showed successful downstaging of 43, all but eight of whom had successful orthoptic liver transplants (Hepatol 2008; 48: 819-827).
Intention-to-treat analysis showed one- and four-year survival rates of 87.5% and 69.3%, respectively. One- and four-year survival after transplantation was 96.2% and 92.1%, respectively.
The authors also cited several small clinical studies that have added support to the ablate-and-wait strategy for patients outside the Milan criteria. Cumulatively, the data suggest that a waiting period of about six months after therapy might be appropriate.
Less evidence has emerged in support of ablate and wait for patients within the Milan criteria. In general, the data suggest that tumor status does not deteriorate between treatment and transplantation.
Geographic variation in the time to transplantation complicates the ablate-and-wait strategy. Roberts and co-authors cited 2007 data showing that 62% of patients underwent liver transplantation within three months after receiving exception points for hepatocellular carcinoma. A shorter waiting time might increase risk of cancer recurrence, but data on recurrence of hepatocellular carcinoma are incomplete.
"The more rapid transplantation rate in some geographic areas is going to create some issues if transplantation is delayed under an ablate-and-wait strategy," the authors acknowledged. "Fortunately, if the wait is six months long, major effects on center transplant numbers are likely to be small."
The authors reported that they had no relevant disclosures.
Primary source: Liver Transplantation
Source reference:
Roberts JP, et al "Hepatocellular carcinoma: ablate and wait versus rapid transplantation" Liver Transpl 2010; DOI: 10.1002/lt.22103.
Source
Published: July 30, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Outcomes in all patients with hepatocellular carcinoma might improve with an "ablate- and-wait" strategy versus rapid transplantation, according to a group of clinicians who have regularly used the strategy.
Use of radiofrequency ablation and chemoembolization to downstage large tumors has shown that about 30% of patients do not qualify for transplantation because of disease progression. The strategy warrants consideration for all patients with hepatocellular carcinoma, regardless of whether they fall within the Milan criteria, according to authors of an article in the August issue of Liver Transplantation.
"Those patients who make it to transplantation have an excellent outcome as compared to patients transplanted with tumors beyond the Milan criteria who are not treated," John Roberts, MD, of the University of California San Francisco, and colleagues wrote in an opinion piece.
"The median time between the first ablative procedure and transplantation was 8.2 months with a range of 3 to 25 months. This approach suggests that the test of time may be the surest method to select patients with hepatocellular carcinoma who are destined to have good transplant outcomes."
The authors argue that their approach of ablating the tumor and then waiting to see whether it recurs or progresses should be expanded to all patients listed for transplantation because of hepatocellular carcinoma. Treating and waiting could help reduce the use of scarce donor organs in patients who will have recurrent disease.
"Our experience with ablative treatment and then observation suggests that the ultimate outcomes of transplantation are not dependent on the primary tumor but more on time spent waiting for transplantation," the authors wrote in their conclusion. "It would seem logical that smaller and/or fewer tumors, though more unlikely to have spread, would also benefit from a period of time if the primary tumor can be controlled."
"The waiting period may be able to decrease the 10% recurrence rate seen in patients transplanted within Milan," they added.
Published more than a decade ago, the Milan criteria for liver transplantation in patients with hepatocellular carcinoma won support because they seemed to identify patients likely to have good transplantation outcomes (N Engl J Med 1996; 334: 693-699). Based on tumor size and number, the criteria fell victim to the same fallacy as other criteria have, according to the authors.
"It has not been shown that there is any particular tumor size that represents no risk of recurrence, at least among those tumors that can be detected radiologically," Roberts and co-authors wrote in their introduction. "Furthermore, the degree of risk is not the same for all patients within the Milan criteria."
The San Francisco group's experience with a strategy of ablate and wait has indicated that patients who fall far outside the Milan criteria do quite well after transplantation, if time is added as a criterion for transplantation. A report covering their experience with 61 patients showed successful downstaging of 43, all but eight of whom had successful orthoptic liver transplants (Hepatol 2008; 48: 819-827).
Intention-to-treat analysis showed one- and four-year survival rates of 87.5% and 69.3%, respectively. One- and four-year survival after transplantation was 96.2% and 92.1%, respectively.
The authors also cited several small clinical studies that have added support to the ablate-and-wait strategy for patients outside the Milan criteria. Cumulatively, the data suggest that a waiting period of about six months after therapy might be appropriate.
Less evidence has emerged in support of ablate and wait for patients within the Milan criteria. In general, the data suggest that tumor status does not deteriorate between treatment and transplantation.
Geographic variation in the time to transplantation complicates the ablate-and-wait strategy. Roberts and co-authors cited 2007 data showing that 62% of patients underwent liver transplantation within three months after receiving exception points for hepatocellular carcinoma. A shorter waiting time might increase risk of cancer recurrence, but data on recurrence of hepatocellular carcinoma are incomplete.
"The more rapid transplantation rate in some geographic areas is going to create some issues if transplantation is delayed under an ablate-and-wait strategy," the authors acknowledged. "Fortunately, if the wait is six months long, major effects on center transplant numbers are likely to be small."
The authors reported that they had no relevant disclosures.
Primary source: Liver Transplantation
Source reference:
Roberts JP, et al "Hepatocellular carcinoma: ablate and wait versus rapid transplantation" Liver Transpl 2010; DOI: 10.1002/lt.22103.
Source
New Cellular 'Armor' Developed to Prevent Infection by AIDS Virus
ScienceDaily (July 30, 2010) — Research by the Consejo Superior de Investigaciones CientÃficas (CSIC) and led by Mr Félix Goñi, director of the Biophysics Unit at the CSIC-University of the Basque Country Mixed Centre, has led to the development of a novel method of attack against the AIDS virus. The method involves creating a prevention system, i.e. an 'armour' in the cells that are likely to be infected and thus impede the virus from accessing them and starting to act on their immunological system.
The study, which appears in the journal Chemistry & Biology, published by Cell Press, lays down the bases of possible future pharmaceutical drugs that will enable combating the AIDS virus at its initial phase. Participating in the research, apart from Mr Goñi, was a team from the National Biotechnology Centre (CSIC-Universidad Autónoma de Madrid) and another from the Institute of Applied Chemistry of Cataloniaa (CSIC, Barcelona).
The research is based on the regulation of the fluidity of the cell membranes and seeks to avoid the phenomenon known as the fusion of membranes, a consequence of contact between the cell membranes and the membrane of the virus itself.
The membrane is the "coating" of the cell cytoplasm and which protects it from the outside, and which has a structure similar to that of the membranes of the AIDS virus. When both membranes come into contact, and due to the fact that the cell membrane is very "fragile," an orifice is created and fusion occurs -- and a route is opened for the AIDS virus to enter, connect to a specific "receptor" of the cell and commence its viral activity.
What the researchers are seeking with this study is to strengthen the membrane structure, making it more rigid, in order to avoid this fusion of membranes and, thus, the inoculation of the cell by the AIDS virus.
Practically all treatment for the AIDS virus currently being applied is based on halting the progress of the virus once it is inside the host cell. There is but one treatment, commercially known as Enfurvitide, which attempts to stop the virus actually entering the cell. The research published in Chemistry & Biology comes to the same conclusion, but by a totally different and novel route.
"For the cell membranes and the virus to come together and this orifice be opened to allow the entrance of the virus, the membranes have to have a certain degree of fluidity, of mobility. We discovered a procedure to make the cell membranes more rigid. This could well give rise to a new pharmaceutical drug which makes the membranes more rigid and impede the entrance of the AIDS virus. Instead of the membrane being flexible, a kind of armour is established which makes the cell impenetrable," explained Félix Goñi.
The research started three years ago and has employed various techniques in the field of chemistry and molecular biology.
At the Institute of Applied Chemistry of Catalonia (CSIC, Barcelona), Ms Gemma Fabriàs has synthesised the GT11 molecule by means of organic chemistry synthesis techniques. Mr Santos Mañes, from the National Biotechnology Centre, studied the viral infection of the cells, and from the Biophysics Unit at the CSIC-University of the Basque Country work has been undertaken at molecular level to demonstrate that there are changes in the rigidity of the membranes when the GT11 molecule is incorporated into them, and that when the membranes are more rigid the virus cannot fuse with the cell membrane and, thus, from penetrating the cell. A highly important role was also placed by Mr José Luis Nieva, from the Biophysics Unit, in studying this fusion of the membranes induced by the AIDS virus.
This scientific discovery by this consortium represents, in the opinion of Mr Goñi, "a completely new means for attacking the virus, and which makes this original."
"There is medication, and which is working very well, to avoid the propagation of the virus once it is inside the cell. But to impede this inoculation in the first place, only one product (Enfurvitide) exists, but this drug is based on a completely distinct principle. The idea of modifying the rigidity of the membranes is completely new and also demonstrating that, by equipping these membranes with greater rigidity, the AIDS virus cannot penetrate," stated Mr Goñi. This same strategy may well serve for other viruses with membrane, such as, for example, the flu virus.
Source
The study, which appears in the journal Chemistry & Biology, published by Cell Press, lays down the bases of possible future pharmaceutical drugs that will enable combating the AIDS virus at its initial phase. Participating in the research, apart from Mr Goñi, was a team from the National Biotechnology Centre (CSIC-Universidad Autónoma de Madrid) and another from the Institute of Applied Chemistry of Cataloniaa (CSIC, Barcelona).
The research is based on the regulation of the fluidity of the cell membranes and seeks to avoid the phenomenon known as the fusion of membranes, a consequence of contact between the cell membranes and the membrane of the virus itself.
The membrane is the "coating" of the cell cytoplasm and which protects it from the outside, and which has a structure similar to that of the membranes of the AIDS virus. When both membranes come into contact, and due to the fact that the cell membrane is very "fragile," an orifice is created and fusion occurs -- and a route is opened for the AIDS virus to enter, connect to a specific "receptor" of the cell and commence its viral activity.
What the researchers are seeking with this study is to strengthen the membrane structure, making it more rigid, in order to avoid this fusion of membranes and, thus, the inoculation of the cell by the AIDS virus.
Practically all treatment for the AIDS virus currently being applied is based on halting the progress of the virus once it is inside the host cell. There is but one treatment, commercially known as Enfurvitide, which attempts to stop the virus actually entering the cell. The research published in Chemistry & Biology comes to the same conclusion, but by a totally different and novel route.
"For the cell membranes and the virus to come together and this orifice be opened to allow the entrance of the virus, the membranes have to have a certain degree of fluidity, of mobility. We discovered a procedure to make the cell membranes more rigid. This could well give rise to a new pharmaceutical drug which makes the membranes more rigid and impede the entrance of the AIDS virus. Instead of the membrane being flexible, a kind of armour is established which makes the cell impenetrable," explained Félix Goñi.
The research started three years ago and has employed various techniques in the field of chemistry and molecular biology.
At the Institute of Applied Chemistry of Catalonia (CSIC, Barcelona), Ms Gemma Fabriàs has synthesised the GT11 molecule by means of organic chemistry synthesis techniques. Mr Santos Mañes, from the National Biotechnology Centre, studied the viral infection of the cells, and from the Biophysics Unit at the CSIC-University of the Basque Country work has been undertaken at molecular level to demonstrate that there are changes in the rigidity of the membranes when the GT11 molecule is incorporated into them, and that when the membranes are more rigid the virus cannot fuse with the cell membrane and, thus, from penetrating the cell. A highly important role was also placed by Mr José Luis Nieva, from the Biophysics Unit, in studying this fusion of the membranes induced by the AIDS virus.
This scientific discovery by this consortium represents, in the opinion of Mr Goñi, "a completely new means for attacking the virus, and which makes this original."
"There is medication, and which is working very well, to avoid the propagation of the virus once it is inside the cell. But to impede this inoculation in the first place, only one product (Enfurvitide) exists, but this drug is based on a completely distinct principle. The idea of modifying the rigidity of the membranes is completely new and also demonstrating that, by equipping these membranes with greater rigidity, the AIDS virus cannot penetrate," stated Mr Goñi. This same strategy may well serve for other viruses with membrane, such as, for example, the flu virus.
Source
Dialysis mix-up prompts discussion over equipment re-use
August 01, 2010 9:00 AM
BARBARA COTTER
THE GAZETTE
For three years, 62-year-old Preston Price has been undergoing dialysis to do what his failing kidneys can’t: filter out impurities in his blood. It’s a process that eats up four hours of his day, three days a week, but typically it’s so uneventful that he tends to doze through it.
In April, however, Price’s routine at Pikes Peak Dialysis Center went awry when he was mistakenly hooked up to a reusable filter, a dialyzer, that belonged to another patient — a person who had a virulent bacterial infection commonly known as MRSA. Price’s health was probably not in danger, his doctors say, and giving one person’s dialyzer to another patient is a mistake that doesn’t happen often at Colorado dialysis centers.
But it happened to Price, and it happened in February at a sister clinic when a patient was given a dialyzer belonging to someone infected with Hepatitis C.
For Pikes Peak Dialysis Center and Printers Place Dialysis Center, both owned by Denver-based DaVita, the mix-ups resulted in an investigation by the Colorado Department of Public Health and Environment.
Investigators cited the centers for failing to notify the department about the incidents and not immediately revising their policies. They also found a number of deficiencies in the centers’ operations, and ordered them to come up with corrective actions to prevent such mix-ups and address unrelated issues, most of them centering around record-keeping.
For dialysis patients, the cases go to the heart of an issue that has long been debated in the medical field but might not be on their radar: Should they opt to be treated with a reusable dialyzer — one that is supposed to be used on that patient only and sterilized after each use? Or is it better to go with single-use dialyzers, which are used once, then tossed?
Re-use became more than a trend
Beginning in the early 1980s, re-use became the status quo. Reusable dialyzers were cheaper, and they didn’t produce the anaphylactic-like “first-use” symptoms associated with single-use dialyzers. In 2000, according to the U.S. Center for Disease Control and Prevention, 80 percent of dialysis centers opted for reusable dialyzers.
But a new generation of single-use dialyzers that were cheaper and less likely to produce first-use issues came on the market. According to a 2007 study by researchers from Tufts University Medical School and Boston’s St. Elizabeth’s Medical Center, the percentage of centers going the re-use route had dropped to 40 percent by 2005.
Still, dialysis experts say re-use is safe — if done correctly and according to quality control standards. That’s a big “if,” however, because re-use relies on a series of human protocols to get everything right, and that boosts the chances for mistakes, the researchers concluded.
“Full compliance in a practical setting ... is difficult to attain, and rigorous quality control standards are vulnerable to poor implementation,” wrote the authors, who declined to be interviewed.
Dr. Michael Lazarus, who taught nephrology at Harvard University, ran the dialysis program at a Boston hospital and is considered a pioneer in the field, put it more succinctly: “When you have humans doing things, they make mistakes.”
Lazarus used to be in the re-use camp, but changed his opinion after he went to work as chief medical officer for a division of Fresenius, a global health company and a major player in the dialysis business. He knows some people will say he became a single-use devotee because Fresenius manufactures the devices, but he said it wouldn’t matter where he worked. Single-use is safer, he contends.
“You remove that potential for human error; it’s gone,” he said.
Mix-ups with reusable dialyzers don’t occur often, though. An official with the Colorado health department said the Colorado Springs cases are the first she’s encountered in seven years at the agency, and Dr. Stephen Fox of Pikes Peak Nephrology Associates said he had seen only one in his 22 years of practice.
“So to have two incidents in a short span of time is very unusual and very troubling,” said Fox.
Lazarus said that getting the wrong dialyzer rarely puts the patient at risk. Sterilization of dialyzers after each use kills most pathogens, including MRSA, he said, so Preston Price is likely in the clear.
“In 99 percent of the cases, it doesn’t matter. It’s like wearing someone else’s underwear; it’s not pleasant, but it doesn’t hurt anyone,” said Lazarus. “There’s a big psychological issue: ‘My blood is going through this artificial kidney that someone else has used.’”
More troubling, he said, is the patient who was exposed to Hepatitis C, because neither that virus nor AIDS can be killed with current sterilization techniques.
And there’s no guarantee that the cleaning and sterilization process will go according to plan. In 2007, a 71-year-old Muskegon, Mich., woman being treated at a DaVita center died after being hooked to a dialyzer that wasn’t properly rinsed after cleaning. The corrosive cleaning agent got into her bloodstream and killed her.
“You can set up all kinds of systems — ‘we’ll do this and we’ll do that’ — but sooner or later, if you don’t have an absolutely perfect system, you’’ll make mistakes,” Lazarus said.
Many companies support single-use only
In the two Springs cases and the one in Michigan, dialysis technicians were blamed for the mistakes, lending ammunition to the argument by Lazarus and the researchers who conducted the 2007 study that re-usable dialyzers leave the door open to potentially serious errors.
In fact, the researchers strongly come down on the side of single-use dialyzers, concluding that “there is no compelling medical indication for reprocessing dialyzers in the new millennium” and the only reason providers like reusable dialyzers is because it saves them money.
But DaVita, second only to Fresenius as the biggest dialysis provider in the U.S., defends its use of reusable dialyzers, and cites a recent article in Nephrology News & Issues showing that seven of the top 10 dialysis operations still offer reusable versions — though DaVita is the only one in El Paso County to do so.
“The reuse of dialyzers is a safe, widely utilized practice throughout the industry,” DaVita spokesman Vince Hancock said in an e-mailed statement.
“The federal government, which oversees dialysis safety, approves reuse of dialyzers through the Association for the Advancement of Medical Instrumentation’s stringent standards which we have always been fully compliant with,” Hancock added. “Also, the National Kidney Foundation has published literature validating that reuse is a safe and commonly accepted practice in kidney care.”
Hancock said there’s independent research showing dialyzer reuse reduces patient exposure to chemicals that coat new dialyzers. It’s true that in the early 2000s, 50 people died from exposure to a chemical used in single-use dialyzers that had not been properly removed before the device was hooked up to a patient.
But Dr. Jesse Flaxenburg of Pikes Peak Nephrology Associates said the chemical is no longer used.
“In other words, advancing technology has made the ‘chemical exposure’ argument a non-starter,” he said.
Flaxenburg and the other doctors at Pikes Peak Nephrology were so alarmed by the back-to-back incidents at the Springs clinics that they sent a letter to their patients in May to say they could “no longer support dialyzer reuse,” and to educate patients on how to protect themselves if they decided to continue with reusable dialyzers. Flaxenburg also said the doctors at the practice, which is being sued by DaVita over an unrelated issue that involves support for a competitor, have started educating patients about the two types of dialyzers since the cases came to light.
“It never really popped into our frame of reference until this,” said Flaxenburg. “It’s a standard educational piece now.”
Hancock says it’s also DaVita’s practice to educate patients about their dialyzers options and give them a choice which to use. Patients then sign a consent form. But Preston Price says he was never given the option, and a few former DaVita patients told doctors they signed a lot of papers when they started dialysis, but don’t recall being informed about their choices.
At this point, the clinics are working with the state on their plans of correction to ensure.
“Patient care is our number one priority, but mistakes can and sometimes do occur,” Hancock said in his statement. “We have rigorous processes and controls in place to minimize errors such as this, but when they do happen we respond aggressively, even when no patient harm occurs. We have also re-emphasized our policies and procedures with our employees to further reduce the likelihood that this could occur again.”
But Preston Price isn’t hanging around to find out. He switched to a competing dialysis provider that does not offer reusable dialyzers, and said the center where he was receiving treatment dropped the ball.
“If you’re a professional, you’re supposed to know what you’re doing,” Price said. “Three people are supposed to check that dialyzer before it goes into my body, but something happened that day, because they let it slip through their hands.”
WASTE NOT
A topic that often comes up in the reuse vs. single-use debate centers on the environment and medical waste. Re-use proponents say single-use dialyzers produce much more waste that ends up in landfills.
“On average, it takes 9.6 reuse dialyzers to treat one patient for a year, versus 153 single-use dialyzers,” said DaVita spokesman Vince Hancock. “Multiply that by the number of patients (on dialysis), and you’re talking about significant environmental reduction in waste.”
A 2007 study by a team from Tufts University and a Boston hospital, however, cites a number of environmental issues associated with reusable dialyzers as well, including the liquid waste from germicides.
They call for more research into the environmental fallout from dialysis, “including the need for more optimal management of disinfectant-related waste with reuse, and solid waster with single-use.”
MORE ABOUT DIALYSIS
There are two main types of dialysis: hemodialysis and peritoneal dialysis. Hemodialysis, the one that’s likely most familiar to people, takes place at a clinic or in a hospital setting, and uses a dialyzer that acts like an artificial kidney to clean the blood. Blood flows from the patient through a tube and into the dialyzer, where it’s cleaned and then pumped back into the body. Peritoneal dialysis essentially uses the body itself and a dialysis solution to clean the blood.
Sources: mayoclinic.com; medicinenet.com
Source
BARBARA COTTER
THE GAZETTE
For three years, 62-year-old Preston Price has been undergoing dialysis to do what his failing kidneys can’t: filter out impurities in his blood. It’s a process that eats up four hours of his day, three days a week, but typically it’s so uneventful that he tends to doze through it.
In April, however, Price’s routine at Pikes Peak Dialysis Center went awry when he was mistakenly hooked up to a reusable filter, a dialyzer, that belonged to another patient — a person who had a virulent bacterial infection commonly known as MRSA. Price’s health was probably not in danger, his doctors say, and giving one person’s dialyzer to another patient is a mistake that doesn’t happen often at Colorado dialysis centers.
But it happened to Price, and it happened in February at a sister clinic when a patient was given a dialyzer belonging to someone infected with Hepatitis C.
For Pikes Peak Dialysis Center and Printers Place Dialysis Center, both owned by Denver-based DaVita, the mix-ups resulted in an investigation by the Colorado Department of Public Health and Environment.
Investigators cited the centers for failing to notify the department about the incidents and not immediately revising their policies. They also found a number of deficiencies in the centers’ operations, and ordered them to come up with corrective actions to prevent such mix-ups and address unrelated issues, most of them centering around record-keeping.
For dialysis patients, the cases go to the heart of an issue that has long been debated in the medical field but might not be on their radar: Should they opt to be treated with a reusable dialyzer — one that is supposed to be used on that patient only and sterilized after each use? Or is it better to go with single-use dialyzers, which are used once, then tossed?
Re-use became more than a trend
Beginning in the early 1980s, re-use became the status quo. Reusable dialyzers were cheaper, and they didn’t produce the anaphylactic-like “first-use” symptoms associated with single-use dialyzers. In 2000, according to the U.S. Center for Disease Control and Prevention, 80 percent of dialysis centers opted for reusable dialyzers.
But a new generation of single-use dialyzers that were cheaper and less likely to produce first-use issues came on the market. According to a 2007 study by researchers from Tufts University Medical School and Boston’s St. Elizabeth’s Medical Center, the percentage of centers going the re-use route had dropped to 40 percent by 2005.
Still, dialysis experts say re-use is safe — if done correctly and according to quality control standards. That’s a big “if,” however, because re-use relies on a series of human protocols to get everything right, and that boosts the chances for mistakes, the researchers concluded.
“Full compliance in a practical setting ... is difficult to attain, and rigorous quality control standards are vulnerable to poor implementation,” wrote the authors, who declined to be interviewed.
Dr. Michael Lazarus, who taught nephrology at Harvard University, ran the dialysis program at a Boston hospital and is considered a pioneer in the field, put it more succinctly: “When you have humans doing things, they make mistakes.”
Lazarus used to be in the re-use camp, but changed his opinion after he went to work as chief medical officer for a division of Fresenius, a global health company and a major player in the dialysis business. He knows some people will say he became a single-use devotee because Fresenius manufactures the devices, but he said it wouldn’t matter where he worked. Single-use is safer, he contends.
“You remove that potential for human error; it’s gone,” he said.
Mix-ups with reusable dialyzers don’t occur often, though. An official with the Colorado health department said the Colorado Springs cases are the first she’s encountered in seven years at the agency, and Dr. Stephen Fox of Pikes Peak Nephrology Associates said he had seen only one in his 22 years of practice.
“So to have two incidents in a short span of time is very unusual and very troubling,” said Fox.
Lazarus said that getting the wrong dialyzer rarely puts the patient at risk. Sterilization of dialyzers after each use kills most pathogens, including MRSA, he said, so Preston Price is likely in the clear.
“In 99 percent of the cases, it doesn’t matter. It’s like wearing someone else’s underwear; it’s not pleasant, but it doesn’t hurt anyone,” said Lazarus. “There’s a big psychological issue: ‘My blood is going through this artificial kidney that someone else has used.’”
More troubling, he said, is the patient who was exposed to Hepatitis C, because neither that virus nor AIDS can be killed with current sterilization techniques.
And there’s no guarantee that the cleaning and sterilization process will go according to plan. In 2007, a 71-year-old Muskegon, Mich., woman being treated at a DaVita center died after being hooked to a dialyzer that wasn’t properly rinsed after cleaning. The corrosive cleaning agent got into her bloodstream and killed her.
“You can set up all kinds of systems — ‘we’ll do this and we’ll do that’ — but sooner or later, if you don’t have an absolutely perfect system, you’’ll make mistakes,” Lazarus said.
Many companies support single-use only
In the two Springs cases and the one in Michigan, dialysis technicians were blamed for the mistakes, lending ammunition to the argument by Lazarus and the researchers who conducted the 2007 study that re-usable dialyzers leave the door open to potentially serious errors.
In fact, the researchers strongly come down on the side of single-use dialyzers, concluding that “there is no compelling medical indication for reprocessing dialyzers in the new millennium” and the only reason providers like reusable dialyzers is because it saves them money.
But DaVita, second only to Fresenius as the biggest dialysis provider in the U.S., defends its use of reusable dialyzers, and cites a recent article in Nephrology News & Issues showing that seven of the top 10 dialysis operations still offer reusable versions — though DaVita is the only one in El Paso County to do so.
“The reuse of dialyzers is a safe, widely utilized practice throughout the industry,” DaVita spokesman Vince Hancock said in an e-mailed statement.
“The federal government, which oversees dialysis safety, approves reuse of dialyzers through the Association for the Advancement of Medical Instrumentation’s stringent standards which we have always been fully compliant with,” Hancock added. “Also, the National Kidney Foundation has published literature validating that reuse is a safe and commonly accepted practice in kidney care.”
Hancock said there’s independent research showing dialyzer reuse reduces patient exposure to chemicals that coat new dialyzers. It’s true that in the early 2000s, 50 people died from exposure to a chemical used in single-use dialyzers that had not been properly removed before the device was hooked up to a patient.
But Dr. Jesse Flaxenburg of Pikes Peak Nephrology Associates said the chemical is no longer used.
“In other words, advancing technology has made the ‘chemical exposure’ argument a non-starter,” he said.
Flaxenburg and the other doctors at Pikes Peak Nephrology were so alarmed by the back-to-back incidents at the Springs clinics that they sent a letter to their patients in May to say they could “no longer support dialyzer reuse,” and to educate patients on how to protect themselves if they decided to continue with reusable dialyzers. Flaxenburg also said the doctors at the practice, which is being sued by DaVita over an unrelated issue that involves support for a competitor, have started educating patients about the two types of dialyzers since the cases came to light.
“It never really popped into our frame of reference until this,” said Flaxenburg. “It’s a standard educational piece now.”
Hancock says it’s also DaVita’s practice to educate patients about their dialyzers options and give them a choice which to use. Patients then sign a consent form. But Preston Price says he was never given the option, and a few former DaVita patients told doctors they signed a lot of papers when they started dialysis, but don’t recall being informed about their choices.
At this point, the clinics are working with the state on their plans of correction to ensure.
“Patient care is our number one priority, but mistakes can and sometimes do occur,” Hancock said in his statement. “We have rigorous processes and controls in place to minimize errors such as this, but when they do happen we respond aggressively, even when no patient harm occurs. We have also re-emphasized our policies and procedures with our employees to further reduce the likelihood that this could occur again.”
But Preston Price isn’t hanging around to find out. He switched to a competing dialysis provider that does not offer reusable dialyzers, and said the center where he was receiving treatment dropped the ball.
“If you’re a professional, you’re supposed to know what you’re doing,” Price said. “Three people are supposed to check that dialyzer before it goes into my body, but something happened that day, because they let it slip through their hands.”
WASTE NOT
A topic that often comes up in the reuse vs. single-use debate centers on the environment and medical waste. Re-use proponents say single-use dialyzers produce much more waste that ends up in landfills.
“On average, it takes 9.6 reuse dialyzers to treat one patient for a year, versus 153 single-use dialyzers,” said DaVita spokesman Vince Hancock. “Multiply that by the number of patients (on dialysis), and you’re talking about significant environmental reduction in waste.”
A 2007 study by a team from Tufts University and a Boston hospital, however, cites a number of environmental issues associated with reusable dialyzers as well, including the liquid waste from germicides.
They call for more research into the environmental fallout from dialysis, “including the need for more optimal management of disinfectant-related waste with reuse, and solid waster with single-use.”
MORE ABOUT DIALYSIS
There are two main types of dialysis: hemodialysis and peritoneal dialysis. Hemodialysis, the one that’s likely most familiar to people, takes place at a clinic or in a hospital setting, and uses a dialyzer that acts like an artificial kidney to clean the blood. Blood flows from the patient through a tube and into the dialyzer, where it’s cleaned and then pumped back into the body. Peritoneal dialysis essentially uses the body itself and a dialysis solution to clean the blood.
Sources: mayoclinic.com; medicinenet.com
Source
'Body's natural cell-suicide program can fuel tumour development'
2010-08-01 17:00:00
Researchers at the Walter and Eliza Hall Institute researchers in Melbourne, Australia, have made a discovery that has turned on its head scientists' understanding of programmed cell death and its role in tumour formation. The body's natural cell-suicide program can add to tumour development, according to the new study.
Programmed cell death (apoptosis) is an important process in human biology as it removes unwanted and damaged cells from our bodies. This process protects us against cancer development and autoimmune disease.
The research team's discovery, led by Professor Andreas Strasser from the institute's Molecular Genetics of Cancer Division, has implications for the understanding of how cancers develop and will inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics.
"Until now everybody believed that a failure of damaged cells to undergo suicide allowed mutated cells to proliferate, which contributes to tumour development. That's certainly still true but we discovered that, in certain settings, the opposite holds: the body's natural cell-suicide program can fuel tumour development," said Professor Strasser.
The research team's experiments revealed that repeated cycles of cellular depletion and tissue regeneration, by activating stem cells, could promote tumour development.
In situations where the DNA in many cells is damaged, such as when the body is repeatedly exposed to low doses of radiation, there are repeated cycles of cell death in the body's tissues.
"Attempts by the body's stem cells to repopulate the depleted tissue can then actually drive the tumour development. That's because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours," said Professor Strasser.
The research, done in collaboration with Dr Ewa Michalak, Dr Cassandra Vandenberg, Mr Alex Delbridge, Dr Li Wu, Dr Clare Scott and Professor Jerry Adams, appears in journal Genes and Development.
Crucial to the team's research was an understanding of what happens to mice exposed to radiation when a gene called Puma is missing.
Professor Strasser said: "If normal mice (which have the Puma gene) are given a low dose of radiation it destroys around 80 per cent of the white blood cells. That does not kill the mouse but it does mean the stem cells in the bone marrow have to work extra hard to replenish the blood system. This can lead to the formation of tumours of white blood cells, called leukaemias, if the stem cells doing the repopulating have cancer-causing mutations.
"The surprise was that mice that don't carry the Puma gene are protected from this type of tumour development. Puma is essential for the death of cells that have damaged DNA. If mice don't have the Puma gene when they receive low doses of radiation the white blood cells are not destroyed, so you don't force mutated stem cells to become activated (and divide) to replenish the blood system."
Professor Strasser said the research suggested that the risk of cancer was increased in people who experienced cycles of tissue destruction followed by tissue re-population by stem cells.
He said: "Such cycles may account for the liver cancers frequently associated with viral (hepatitis C) infection or alcohol-related liver damage."
The research also helps explain the so-called secondary cancers that sometimes arise in patients who were cured of their primary cancer by chemotherapeutic drugs that cause DNA damage." he findings will also inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics. These drugs are designed to kill cancer cells.
Professor Strasser said: "Chronic exposure to such drugs could lead to the death of large numbers of normal cells that would then need to be replaced. In certain circumstances this could promote the development of secondary cancers, particularly if patients are receiving treatments such as chemotherapy or gamma-radiation that can lead to cancer-causing mutations in stem cells." (ANI)
Source
Researchers at the Walter and Eliza Hall Institute researchers in Melbourne, Australia, have made a discovery that has turned on its head scientists' understanding of programmed cell death and its role in tumour formation. The body's natural cell-suicide program can add to tumour development, according to the new study.
Programmed cell death (apoptosis) is an important process in human biology as it removes unwanted and damaged cells from our bodies. This process protects us against cancer development and autoimmune disease.
The research team's discovery, led by Professor Andreas Strasser from the institute's Molecular Genetics of Cancer Division, has implications for the understanding of how cancers develop and will inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics.
"Until now everybody believed that a failure of damaged cells to undergo suicide allowed mutated cells to proliferate, which contributes to tumour development. That's certainly still true but we discovered that, in certain settings, the opposite holds: the body's natural cell-suicide program can fuel tumour development," said Professor Strasser.
The research team's experiments revealed that repeated cycles of cellular depletion and tissue regeneration, by activating stem cells, could promote tumour development.
In situations where the DNA in many cells is damaged, such as when the body is repeatedly exposed to low doses of radiation, there are repeated cycles of cell death in the body's tissues.
"Attempts by the body's stem cells to repopulate the depleted tissue can then actually drive the tumour development. That's because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours," said Professor Strasser.
The research, done in collaboration with Dr Ewa Michalak, Dr Cassandra Vandenberg, Mr Alex Delbridge, Dr Li Wu, Dr Clare Scott and Professor Jerry Adams, appears in journal Genes and Development.
Crucial to the team's research was an understanding of what happens to mice exposed to radiation when a gene called Puma is missing.
Professor Strasser said: "If normal mice (which have the Puma gene) are given a low dose of radiation it destroys around 80 per cent of the white blood cells. That does not kill the mouse but it does mean the stem cells in the bone marrow have to work extra hard to replenish the blood system. This can lead to the formation of tumours of white blood cells, called leukaemias, if the stem cells doing the repopulating have cancer-causing mutations.
"The surprise was that mice that don't carry the Puma gene are protected from this type of tumour development. Puma is essential for the death of cells that have damaged DNA. If mice don't have the Puma gene when they receive low doses of radiation the white blood cells are not destroyed, so you don't force mutated stem cells to become activated (and divide) to replenish the blood system."
Professor Strasser said the research suggested that the risk of cancer was increased in people who experienced cycles of tissue destruction followed by tissue re-population by stem cells.
He said: "Such cycles may account for the liver cancers frequently associated with viral (hepatitis C) infection or alcohol-related liver damage."
The research also helps explain the so-called secondary cancers that sometimes arise in patients who were cured of their primary cancer by chemotherapeutic drugs that cause DNA damage." he findings will also inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics. These drugs are designed to kill cancer cells.
Professor Strasser said: "Chronic exposure to such drugs could lead to the death of large numbers of normal cells that would then need to be replaced. In certain circumstances this could promote the development of secondary cancers, particularly if patients are receiving treatments such as chemotherapy or gamma-radiation that can lead to cancer-causing mutations in stem cells." (ANI)
Source
Hepatitis C Remains a Major Health Challenge for HIV-infected Persons
by VR Sreeraman on August 01, 2010 at 12:14 PM
Hepatitis C virus (HCV) co-infection occurs in an estimated one quarter of HIV-infected persons in Europe, Australia, and the United States. “As use of highly active antiretroviral drugs has markedly reduced opportunistic infections, HCV-related liver disease has emerged as a leading cause of death. HIV infection adversely affects both the natural history and the treatment of hepatitis C” said Dr David L Thomas, Division of Infectious Diseases, Johns Hopkins School of Medicine, USA.
For people living with HIV (PLHIV) Hepatitis C (Hep C) is a major public health challenge that can and should be controlled.
“We have a serious condition and we have clear evidence that it can be controlled” said Dr David Thomas.
Two clear solid grounds why it is important to control HCV are: It is common and very severe.
The incidence of Hep C is scary – in Baltimore, Europe or Australia, HCV occurs in 70% to up to 100% among PLHIV who acquire infection through injecting drug use (IDU).
In India, whether it is Chennai in South India, or north-east India, Hep C rates among PLHIV who acquire HIV through injecting drug use are very similar and shocking. However there are several others who just have HCV and not HIV, said Dr David.
Hep C also infects PLHIV who acquired infection through heterosexual or homosexual routes.
60% of persons who acquire HCV go on to have chronic hepatitis infection. HCV viral load is also high if person is co-infected with HIV.
“HIV decreases response to HCV treatment – can have half of treatment outcome than HIV negative individuals” said Dr David Thomas. HCV treatment costs are over USD 20,000 per person.
HIV infection adversely affects all stages of Hep C or HCV infection.
“Risk of liver failure was higher among individuals living with HIV than those individuals who were similar with regards to HCV but HIV negative” said Dr Thomas.
The antiretroviral (ARV) therapy is not sufficient to:
• Reduce the HCV RNA load
• Restore treatment response
• Prevent cirrhosis or liver failure
However antiretroviral therapy (ART) significantly reduces mortality among people co-infected with HIV and HCV.
“Markedly lower survival for HIV/HCV co-infected persons was observed in Denmark (2000-2005)” said Dr Thomas.
HCV transmission can be prevented. Dr Thomas listed few clear points of action to prevent HCV:
• Transfusion transmission has stopped where screening is done
• Nosocomial spread reduced where bloodborne precautions observed
• HCV incidence among IDU has declined
“Even in places where harm reduction measures are in place, HCV continues. HCV is more transmissible than HIV, so measures to control HIV are not going to be enough, they need to be intensified” said Dr Thomas.
Very few people co-infected with HIV and HCV are currently receiving testing, and treatment for HCV.
There is a clear need for harm reduction measures to intensified and expanded, testing for HCV to be expanded and HCV treatment be made available widely.
“Let’s rejoice in the fact that today we have treatments that work... what we need I the political will to go the extra mile to deliver universal access” had said J Montaner, which is so much in context to improve responses to HCV and HIV co-infection.
Contributed by: Bobby Ramakant
Source-Medindia
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