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
August 1, 2010
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 Clínic, 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 Clínic, 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 Científicas (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
Source
July 30, 2010
Miracle Mineral Solution (MMS): Product as consumed produces a potent bleach
[Posted 07/30/2010]
AUDIENCE: Consumers, Emergency Medicine
ISSUE: FDA warned consumers not to consume or use Miracle Mineral Solution, an oral liquid solution also known as "Miracle Mineral Supplement" or "MMS." The product, when used as directed, produces an industrial bleach that can cause serious harm to health. The product instructs consumers to mix the 28 percent sodium chlorite solution with an acid such as citrus juice. This mixture produces chlorine dioxide, a potent bleach used for stripping textiles and industrial water treatment. High oral doses of this bleach, such as those recommended in the labeling, can cause nausea, vomiting, diarrhea, and symptoms of severe dehydration.
BACKGROUND: MMS is distributed on Internet sites and online auctions by multiple independent distributors. MMS claims to treat multiple unrelated diseases, including HIV, hepatitis, the H1N1 flu virus, common colds, acne, cancer, and other conditions. The FDA is not aware of any research that MMS is effective in treating any of these conditions. MMS also poses a significant health risk to consumers who may choose to use this product for self-treatment instead of seeking FDA-approved treatments for these conditions.
RECOMMENDATIONS: Consumers who have MMS should stop using it immediately and throw it away. The FDA advises consumers who have experienced any negative side effects from MMS to consult a health care professional as soon as possible.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of this product to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
Online: www.fda.gov/MedWatch/report.htm
Phone: 1-800-332-1088
Mail: return the postage-paid FDA form 3500, which may be downloaded from the MedWatch "Download Forms" page, to address on the pre-addressed form
Fax: 1-800-FDA-0178
[07/30/2010 - News Release - FDA]
Source
AUDIENCE: Consumers, Emergency Medicine
ISSUE: FDA warned consumers not to consume or use Miracle Mineral Solution, an oral liquid solution also known as "Miracle Mineral Supplement" or "MMS." The product, when used as directed, produces an industrial bleach that can cause serious harm to health. The product instructs consumers to mix the 28 percent sodium chlorite solution with an acid such as citrus juice. This mixture produces chlorine dioxide, a potent bleach used for stripping textiles and industrial water treatment. High oral doses of this bleach, such as those recommended in the labeling, can cause nausea, vomiting, diarrhea, and symptoms of severe dehydration.
BACKGROUND: MMS is distributed on Internet sites and online auctions by multiple independent distributors. MMS claims to treat multiple unrelated diseases, including HIV, hepatitis, the H1N1 flu virus, common colds, acne, cancer, and other conditions. The FDA is not aware of any research that MMS is effective in treating any of these conditions. MMS also poses a significant health risk to consumers who may choose to use this product for self-treatment instead of seeking FDA-approved treatments for these conditions.
RECOMMENDATIONS: Consumers who have MMS should stop using it immediately and throw it away. The FDA advises consumers who have experienced any negative side effects from MMS to consult a health care professional as soon as possible.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of this product to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
Online: www.fda.gov/MedWatch/report.htm
Phone: 1-800-332-1088
Mail: return the postage-paid FDA form 3500, which may be downloaded from the MedWatch "Download Forms" page, to address on the pre-addressed form
Fax: 1-800-FDA-0178
[07/30/2010 - News Release - FDA]
Source
Improving the Inhibitory Control Task to Detect Minimal Hepatic Encephalopathy
Gastroenterology
Volume 139, Issue 2 , Pages 510-518.e2, August 2010
Piero Amodio, Lorenzo Ridola, Sami Schiff, Sara Montagnese, Chiara Pasquale, Silvia Nardelli, Ilaria Pentassuglio, Maria Trezza, Chiara Marzano, Cristiana Flaiban, Paolo Angeli, Giorgio Cona, Patrizia Bisiacchi, Angelo Gatta, Oliviero Riggio
Received 31 December 2009; accepted 29 April 2010. published online 13 May 2010.
Abstract
Background & Aims
Quantification of the number of noninhibited responses (lures) in the inhibitory control task (ICT) has been proposed for the diagnosis of minimal hepatic encephalopathy (MHE). We assessed the efficacy of ICT compared with recommended diagnostic standards.
Methods
We studied patients with cirrhosis and healthy individuals (controls) who underwent the ICT at 2 centers (center A: n = 51 patients and 41 controls, center B: n = 24 patients and 14 controls). Subjects were evaluated for MHE by psychometric hepatic encephalopathy score (PHES). Patients from center B also were assessed for MHE by critical flicker frequency and spectral electroencephalogram analyses.
Results
Patients with cirrhosis had higher ICT lures (23.2 ± 12.8 vs 12.9 ± 5.8, respectively, P < .01) and lower ICT target accuracy (0.88 ± 0.17 vs 0.96 ± 0.03, respectively, P < .01) compared with controls. However, lures were comparable (25.2 ± 12.5 vs 21.4 ± 13.9, respectively, P = .32) among patients with/without altered PHES (center A). There was a reverse, U-shaped relationship between ICT lure and target accuracy; a variable adjusting lures was devised based on target accuracy (weighted lures at center B). This variable differed between patients with and without MHE. The variable weighted lures was then validated from data collected at center A by receiver operator characteristic curve analysis; it discriminated between patients with and without PHES alterations (area under the curve = 0.71 ± 0.07). However, target accuracy alone was as effective as a stand-alone variable (area under the curve = 0.81 ± 0.06).
Conclusions
The ICT is not useful for the diagnosis of MHE, unless adjusted by target accuracy. Testing inhibition (lures) does not seem to be superior to testing attention (target accuracy) for the detection of MHE.
Keywords: Electroencephalogram, EEG, Attention, Inhibition
Abbreviations used in this paper: CFF, critical flicker frequency, EEG, electroencephalogram, ICT, inhibitory control task, HE, hepatic encephalopathy, LTT, line tracing test, MHE, minimal hepatic encephalopathy, PHES, psychometric hepatic encephalopathy score, ROC, receiving operative curves, TMT, trail making test, WL, weighted lures.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants of the University of Padua (to P.A.) and of the University of Rome (to O.R.) and by a “Young Investigator Award” given (to L.R.) by the Italian Society of Gastroenterology (SIGE).
PII: S0016-5085(10)00677-3
doi:10.1053/j.gastro.2010.04.057
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Volume 139, Issue 2 , Pages 510-518.e2, August 2010
Piero Amodio, Lorenzo Ridola, Sami Schiff, Sara Montagnese, Chiara Pasquale, Silvia Nardelli, Ilaria Pentassuglio, Maria Trezza, Chiara Marzano, Cristiana Flaiban, Paolo Angeli, Giorgio Cona, Patrizia Bisiacchi, Angelo Gatta, Oliviero Riggio
Received 31 December 2009; accepted 29 April 2010. published online 13 May 2010.
Abstract
Background & Aims
Quantification of the number of noninhibited responses (lures) in the inhibitory control task (ICT) has been proposed for the diagnosis of minimal hepatic encephalopathy (MHE). We assessed the efficacy of ICT compared with recommended diagnostic standards.
Methods
We studied patients with cirrhosis and healthy individuals (controls) who underwent the ICT at 2 centers (center A: n = 51 patients and 41 controls, center B: n = 24 patients and 14 controls). Subjects were evaluated for MHE by psychometric hepatic encephalopathy score (PHES). Patients from center B also were assessed for MHE by critical flicker frequency and spectral electroencephalogram analyses.
Results
Patients with cirrhosis had higher ICT lures (23.2 ± 12.8 vs 12.9 ± 5.8, respectively, P < .01) and lower ICT target accuracy (0.88 ± 0.17 vs 0.96 ± 0.03, respectively, P < .01) compared with controls. However, lures were comparable (25.2 ± 12.5 vs 21.4 ± 13.9, respectively, P = .32) among patients with/without altered PHES (center A). There was a reverse, U-shaped relationship between ICT lure and target accuracy; a variable adjusting lures was devised based on target accuracy (weighted lures at center B). This variable differed between patients with and without MHE. The variable weighted lures was then validated from data collected at center A by receiver operator characteristic curve analysis; it discriminated between patients with and without PHES alterations (area under the curve = 0.71 ± 0.07). However, target accuracy alone was as effective as a stand-alone variable (area under the curve = 0.81 ± 0.06).
Conclusions
The ICT is not useful for the diagnosis of MHE, unless adjusted by target accuracy. Testing inhibition (lures) does not seem to be superior to testing attention (target accuracy) for the detection of MHE.
Keywords: Electroencephalogram, EEG, Attention, Inhibition
Abbreviations used in this paper: CFF, critical flicker frequency, EEG, electroencephalogram, ICT, inhibitory control task, HE, hepatic encephalopathy, LTT, line tracing test, MHE, minimal hepatic encephalopathy, PHES, psychometric hepatic encephalopathy score, ROC, receiving operative curves, TMT, trail making test, WL, weighted lures.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants of the University of Padua (to P.A.) and of the University of Rome (to O.R.) and by a “Young Investigator Award” given (to L.R.) by the Italian Society of Gastroenterology (SIGE).
PII: S0016-5085(10)00677-3
doi:10.1053/j.gastro.2010.04.057
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Hepatic ISG Expression Is Associated With Genetic Variation in Interleukin 28B and the Outcome of IFN Therapy for Chronic Hepatitis C
Gastroenterology
Volume 139, Issue 2 , Pages 499-509, August 2010
Masao Honda, Akito Sakai, Tatsuya Yamashita, Yasunari Nakamoto, Eishiro Mizukoshi, Yoshio Sakai, Taro Yamashita, Mikiko Nakamura, Takayoshi Shirasaki, Katsuhisa Horimoto, Yasuhito Tanaka, Katsushi Tokunaga, Masashi Mizokami, Shuichi Kaneko, Hokuriku Liver Study Group
Received 9 October 2009; accepted 14 April 2010. published online 30 April 2010.
Abstract
Background & Aims
Multiple viral and host factors are related to the treatment response to pegylated-interferon and ribavirin combination therapy; however, the clinical relevance and relationship of these factors have not yet been fully evaluated.
Methods
We studied 168 patients with chronic hepatitis C who received pegylated-interferon and ribavirin combination therapy. Gene expression profiles in the livers of 91 patients were analyzed using an Affymetrix genechip (Affymetrix, Santa Clara, CA). The expression of interferon-stimulated genes (ISGs) was evaluated in all samples by real-time polymerase chain reaction. Genetic variation in interleukin 28B (IL28B; rs8099917) was determined in 91 patients.
Results
Gene expression profiling of the liver differentiated patients into 2 groups: patients with up-regulated ISGs and patients with down-regulated ISGs. A high proportion of patients with no response to treatment was found in the up-regulated ISGs group (P = .002). Multivariate logistic regression analysis showed that ISGs (<3.5) (odds ratio [OR], 16.2; P < .001), fibrosis stage (F1-F2) (OR, 4.18; P = .003), and ISDR mutation (≥2) (OR, 5.09; P = .003) were strongly associated with the viral response. The IL28B polymorphism of 91 patients showed that 66% were major homozygotes (TT), 30% were heterozygotes (TG), and 4% were minor homozygotes (GG). Interestingly, hepatic ISGs were associated with the IL28B polymorphism (OR, 18.1; P < .001), and its expression was significantly higher in patients with the minor genotype (TG or GG) than in those with the major genotype (TT).
Conclusions
The expression of hepatic ISGs is strongly associated with treatment response and genetic variation of IL28B. The differential role of host and viral factors as predicting factors may also be present.
Keywords: Pegylated Interferon, Ribavirin, Gene Expression, Single Nucleotide Polymorphism
Abbreviations used in this paper: aa, amino acid, AST, aspartate aminotransferase, cDNA, complementary DNA, CH-C, chronic hepatitis C, Down-ISGs, down-regulated ISGs, EVR, early virologic response, GWAS, genome-wide association studies, HCV, hepatitis C virus, IFN, interferon, IFI44, interferon-induced protein 44, IFIT1, interferon-induced protein with tetratricopeptide repeats 1, IL, interleukin, IL28B, interleukin 28B, ISDR, interferon sensitivity determining region, ISGs, interferon stimulated genes, Mx1, myxovirus (influenza virus) resistance 1 interferon-inducible protein p78 (mouse), NR, no response, Peg, pegylated, RBV, ribavirin, ROC, receiver operating characteristic, RTD, real-time detection, PCR, polymerase chain reaction, RTD-PCR, real-time detection-polymerase chain reaction, SNP, single nucleotide polymorphism, SVR, sustained viral response, TR, transient response, Up-ISGs, up-regulated ISGs
Participating investigators are listed in Appendix 1.
Conflicts of interest The authors disclose no conflicts.
Funding This work was supported in part by a grant-in-aid from the Ministry of Health, Labour and Welfare of Japan.
PII: S0016-5085(10)00657-8
doi:10.1053/j.gastro.2010.04.049
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Volume 139, Issue 2 , Pages 499-509, August 2010
Masao Honda, Akito Sakai, Tatsuya Yamashita, Yasunari Nakamoto, Eishiro Mizukoshi, Yoshio Sakai, Taro Yamashita, Mikiko Nakamura, Takayoshi Shirasaki, Katsuhisa Horimoto, Yasuhito Tanaka, Katsushi Tokunaga, Masashi Mizokami, Shuichi Kaneko, Hokuriku Liver Study Group
Received 9 October 2009; accepted 14 April 2010. published online 30 April 2010.
Abstract
Background & Aims
Multiple viral and host factors are related to the treatment response to pegylated-interferon and ribavirin combination therapy; however, the clinical relevance and relationship of these factors have not yet been fully evaluated.
Methods
We studied 168 patients with chronic hepatitis C who received pegylated-interferon and ribavirin combination therapy. Gene expression profiles in the livers of 91 patients were analyzed using an Affymetrix genechip (Affymetrix, Santa Clara, CA). The expression of interferon-stimulated genes (ISGs) was evaluated in all samples by real-time polymerase chain reaction. Genetic variation in interleukin 28B (IL28B; rs8099917) was determined in 91 patients.
Results
Gene expression profiling of the liver differentiated patients into 2 groups: patients with up-regulated ISGs and patients with down-regulated ISGs. A high proportion of patients with no response to treatment was found in the up-regulated ISGs group (P = .002). Multivariate logistic regression analysis showed that ISGs (<3.5) (odds ratio [OR], 16.2; P < .001), fibrosis stage (F1-F2) (OR, 4.18; P = .003), and ISDR mutation (≥2) (OR, 5.09; P = .003) were strongly associated with the viral response. The IL28B polymorphism of 91 patients showed that 66% were major homozygotes (TT), 30% were heterozygotes (TG), and 4% were minor homozygotes (GG). Interestingly, hepatic ISGs were associated with the IL28B polymorphism (OR, 18.1; P < .001), and its expression was significantly higher in patients with the minor genotype (TG or GG) than in those with the major genotype (TT).
Conclusions
The expression of hepatic ISGs is strongly associated with treatment response and genetic variation of IL28B. The differential role of host and viral factors as predicting factors may also be present.
Keywords: Pegylated Interferon, Ribavirin, Gene Expression, Single Nucleotide Polymorphism
Abbreviations used in this paper: aa, amino acid, AST, aspartate aminotransferase, cDNA, complementary DNA, CH-C, chronic hepatitis C, Down-ISGs, down-regulated ISGs, EVR, early virologic response, GWAS, genome-wide association studies, HCV, hepatitis C virus, IFN, interferon, IFI44, interferon-induced protein 44, IFIT1, interferon-induced protein with tetratricopeptide repeats 1, IL, interleukin, IL28B, interleukin 28B, ISDR, interferon sensitivity determining region, ISGs, interferon stimulated genes, Mx1, myxovirus (influenza virus) resistance 1 interferon-inducible protein p78 (mouse), NR, no response, Peg, pegylated, RBV, ribavirin, ROC, receiver operating characteristic, RTD, real-time detection, PCR, polymerase chain reaction, RTD-PCR, real-time detection-polymerase chain reaction, SNP, single nucleotide polymorphism, SVR, sustained viral response, TR, transient response, Up-ISGs, up-regulated ISGs
Participating investigators are listed in Appendix 1.
Conflicts of interest The authors disclose no conflicts.
Funding This work was supported in part by a grant-in-aid from the Ministry of Health, Labour and Welfare of Japan.
PII: S0016-5085(10)00657-8
doi:10.1053/j.gastro.2010.04.049
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Chronic Hepatitis C Virus Infection Is Associated with Early Atherosclerosis
SUMMARY: People with chronic hepatitis C are more likely than those never infected to have diabetes and visceral fat accumulation, but have lower levels of LDL "bad" cholesterol, according to a study described in the June 28, 2010 advance online issue of Gut. After HCV clearance, LDL levels rose to match those of never-infected individuals, but glucose levels and abdominal fat remained similar. After adjusting for other risk factors, chronic hepatitis C patients had greater carotid intima-media thickness, an indicator of the early stages of atherosclerosis.
By Liz Highleyman
Previous research has found that people with chronic hepatitis C virus (HCV) infection have an elevated risk for cardiovascular disease. While HCV has been linked to insulin resistance or diabetes -- known risk factors for heart disease -- it is also typically characterized by favorable blood lipid levels.
In the present study, Aya Mostafa from AinShams University in Cairo and colleagues looked at the effect of this paradoxical risk profile on metabolism and atherosclerosis (hardening of the arteries and build-up of plaque) in the setting of HCV infection and clearance.
This cross-sectional analysis included more than 1200 participants in Egypt aged 35 years or older. Within this study population, 329 had chronic hepatitis C, 173 had cleared HCV infection, and 795 were never infected with HCV; a subset of 192, 115, and 187 participants, respectively, from the 3 groups underwent ultrasound imaging.
The investigators evaluated presence of diabetes, fasting blood glucose, lipid levels, and body fat deposition using ultrasound. Carotid intima-media thickness (IMT), or width of the inner lining of the carotid arteries supplying the brain, was used as a measure of atherosclerosis.
Results
"These different cardiovascular risk patterns may determine equivalent atherosclerosis risk by infection status," they suggested. "However, once these factors were accounted for, those with chronic infection had raised IMT, suggesting a direct effect of infection."
Department of Community Medicine, Faculty of Medicine, AinShams University, Cairo, Egypt; Department of Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt; Viral Hepatitis Reference Laboratory, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Institut Pasteur, Paris, France; Department of Metabolic Medicine, Imperial College NHS Healthcare Trust, London, UK; International Centre for Circulatory Health, National Heart & Lung Institute, Imperial College NHS Healthcare Trust, London, UK; Faculty of Medicine, Minia University, Minia, Egypt.
7/30/10
Reference
A Mostafa, MK Mohamed, M Saeed, and others. Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors. Gut (Abstract). June 28, 2010 (Epub ahead of print).
Source
By Liz Highleyman
Previous research has found that people with chronic hepatitis C virus (HCV) infection have an elevated risk for cardiovascular disease. While HCV has been linked to insulin resistance or diabetes -- known risk factors for heart disease -- it is also typically characterized by favorable blood lipid levels.
In the present study, Aya Mostafa from AinShams University in Cairo and colleagues looked at the effect of this paradoxical risk profile on metabolism and atherosclerosis (hardening of the arteries and build-up of plaque) in the setting of HCV infection and clearance.
This cross-sectional analysis included more than 1200 participants in Egypt aged 35 years or older. Within this study population, 329 had chronic hepatitis C, 173 had cleared HCV infection, and 795 were never infected with HCV; a subset of 192, 115, and 187 participants, respectively, from the 3 groups underwent ultrasound imaging.
The investigators evaluated presence of diabetes, fasting blood glucose, lipid levels, and body fat deposition using ultrasound. Carotid intima-media thickness (IMT), or width of the inner lining of the carotid arteries supplying the brain, was used as a measure of atherosclerosis.
Results
- Diabetes was more common among participants with chronic hepatitis C and cleared HCV infection (both with a prevalence of 10.1%) than among those who never had HCV (6.6%; P = 0.04 for chronic, 0.08 for cleared).
- The amount of mesenteric or visceral fat was greater in people with chronic hepatitis C (36.4 mm) and cleared infection (37.8 mm) relative to those never infected (32.7 mm; P = 0.004 for chronic, < 0.0001 for cleared).
- Low-density lipoprotein (LDL) cholesterol levels were lower in the chronic hepatitis C group (2.69 mmol/L; P < 0.001), but similar in those with cleared infection (3.56 mmol/L; P = 0.4) and those never infected (3.45 mmol/L).
- Carotid IMT did not differ significantly according to HCV infection status, at 0.73, 0.71, and 0.71 mm, respectively.
- After adjustmenting for traditional cardiovascular risk factors, however, IMT was greater in peoplewith chronic infection (0.76 mm) compared with never infected individuals (0.70 mm; P = 0.02).
"These different cardiovascular risk patterns may determine equivalent atherosclerosis risk by infection status," they suggested. "However, once these factors were accounted for, those with chronic infection had raised IMT, suggesting a direct effect of infection."
Department of Community Medicine, Faculty of Medicine, AinShams University, Cairo, Egypt; Department of Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt; Viral Hepatitis Reference Laboratory, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Institut Pasteur, Paris, France; Department of Metabolic Medicine, Imperial College NHS Healthcare Trust, London, UK; International Centre for Circulatory Health, National Heart & Lung Institute, Imperial College NHS Healthcare Trust, London, UK; Faculty of Medicine, Minia University, Minia, Egypt.
7/30/10
Reference
A Mostafa, MK Mohamed, M Saeed, and others. Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors. Gut (Abstract). June 28, 2010 (Epub ahead of print).
Source
Organ donor shortage makes survival a long shot
By Sandra V. Rodriguez • srodriguez@citizen-times.com • July 30, 2010
ASHEVILLE — Julie Wallace always said yes to organ donation.
But in recent years, the little heart on her driver's license has held deeper meaning because she came so close to losing her 12-year-old son, Jacob. Both of his kidneys failed nine years ago, when Jacob was 3.
“It was a nightmare,” she said. “I literally just prayed every night that he would make it. It's a rough thing when you're waiting for a transplant for a loved one because you know that someone else's loved one has to pass away…”
That someone was a woman who suffered a fatal aneurysm while exercising. She left behind children and a husband, who consented to donate her organs. The woman gave at least seven people a second chance at life.
There are more than 3,300 North Carolinians included in the transplant waiting. Unfortunately for many, the number of donors isn't keeping up.
Kirk Truesdale was diagnosed with hepatitis C five years ago, but doctors didn't catch it in time to save his liver. Truesdale has been on the transplant waiting list for nearly three years. At one time, he was moved to hospice care because of how sick he became. His wife, Shirley, even began making funeral arrangements.
“A lot of people don't understand the things that you go through when you're waiting for a transplant,” Shirley said. “You're dealing with a very sick person that if you let yourself think about a lot, you'll feel like the sand is running out in the glass.”
Truesdale knows his sickness is harder on his wife and 12-year-old daughter, Keeley, than it is on him. The ammonia buildup in the one-time ironworker's body often leads to his legs or belly swelling up with fluid. This causes what Shirley describes as Alzheimer's-like behavior in Truesdale, who can get combative or ramble endlessly or wander off during these spells.
“It's been hell,” he said. “There are times when you want to just say to God, ‘Just take me.'”
The state has made strides to increase donor registration in recent years by making it easier to register in person at the Department of Motor Vehicles or online or at DonateLifeNC.org, and passing the Heart Prevails law in 2007. It turned the heart on the driver's license from a symbol of intent to donate to legal consent for organ and eye
“In the past, I think people realized it didn't mean a whole lot because they knew the family could override it,” Melissa Parker, organ procurement specialist with LifeShare of the Carolinas' office in Asheville. The nonprofit provides tissues and organs for transplantation for people in southwestern North Carolina. “But now that heart means something.”
Parker has worked with donors for the last 15 years, and she's never seen the waiting list numbers go down. When she first started doing this job, there were about 30,000 people on the waiting list, and now it's nearly 108,000. The list increases by one every 12 minutes, according to Carolina Donor Services.
The situation is especially critical for kidney transplants for minorities who make up “disproportionately” high number of people on the waiting list, said Debbie Gibbs, with LifeShare in Charlotte.
It's largely because of high blood pressure and diabetes, which are more common in the African-American, Hispanic and Native American communities.
In North Carolina, 60 percent of the kidney transplant waiting list is made up of African-Americans as opposed to 35 percent nationwide. The state's donor rate for African-Americans was 26 percent in 2009.
Generally, Parker said race does not play a role in who gets an organ transplant. For any transplant, the most important factor is always blood type. But it would be best, in cases of kidney or pancreas transplants, that a person received the organ from someone who has similar tissue, she said.
“We never think that someone in our family or one of our close friends is going to need a transplant,” Wallace said. “He (Jacob) was born a completely healthy child, and some freak illness caused him to be very ill. He would have died, absolutely, at age 5 had we not gotten his transplant.”
Even now, eight years after the “nightmare” ended, the fear and worry are never far. Wallace still gets anxious when Jacob shows signs of fever.
That's something new parents Larry and Meghan Robertson understand intimately. The couple's 7-month-old baby, Ty, was born without a right kidney, and the left one is only one-third its normal size. The doctors had very little hope that he would make it. It was devastating news for the couple, who had spun so many dreams in the last nine months.
“It's not what any mother looks for when she says, ‘I'm pregnant,'” Meghan said. “I didn't think about my baby being in NICU (neonatal intensive care unit) and going through all this.”
While families everywhere were waiting for Santa, Meghan spent last Christmas Eve in a Winston-Salem hospital praying that her baby would make it through the night.
But what a difference a few months makes. With the help of a dialysis machine, 7-month-old Ty has shown strength of will that makes his parents hopeful that he will hold on long enough to get on the national organ transplant waiting list.
It's hard to tell how long the wait will be for Ty once he gets on the list. He needs to weigh 22 pounds before that happens. But the Robertsons' family and friends are hoping to speed the process along by getting tested to see if there is a match.
“I want to see him grow up,” Meghan said. “I want to see him go to school. Go to college. Get married and have my grandbabies. I want to see all that, and I hope that he is more than able to do it.”
Source
ASHEVILLE — Julie Wallace always said yes to organ donation.
But in recent years, the little heart on her driver's license has held deeper meaning because she came so close to losing her 12-year-old son, Jacob. Both of his kidneys failed nine years ago, when Jacob was 3.
“It was a nightmare,” she said. “I literally just prayed every night that he would make it. It's a rough thing when you're waiting for a transplant for a loved one because you know that someone else's loved one has to pass away…”
That someone was a woman who suffered a fatal aneurysm while exercising. She left behind children and a husband, who consented to donate her organs. The woman gave at least seven people a second chance at life.
There are more than 3,300 North Carolinians included in the transplant waiting. Unfortunately for many, the number of donors isn't keeping up.
Kirk Truesdale was diagnosed with hepatitis C five years ago, but doctors didn't catch it in time to save his liver. Truesdale has been on the transplant waiting list for nearly three years. At one time, he was moved to hospice care because of how sick he became. His wife, Shirley, even began making funeral arrangements.
“A lot of people don't understand the things that you go through when you're waiting for a transplant,” Shirley said. “You're dealing with a very sick person that if you let yourself think about a lot, you'll feel like the sand is running out in the glass.”
Truesdale knows his sickness is harder on his wife and 12-year-old daughter, Keeley, than it is on him. The ammonia buildup in the one-time ironworker's body often leads to his legs or belly swelling up with fluid. This causes what Shirley describes as Alzheimer's-like behavior in Truesdale, who can get combative or ramble endlessly or wander off during these spells.
“It's been hell,” he said. “There are times when you want to just say to God, ‘Just take me.'”
The state has made strides to increase donor registration in recent years by making it easier to register in person at the Department of Motor Vehicles or online or at DonateLifeNC.org, and passing the Heart Prevails law in 2007. It turned the heart on the driver's license from a symbol of intent to donate to legal consent for organ and eye
“In the past, I think people realized it didn't mean a whole lot because they knew the family could override it,” Melissa Parker, organ procurement specialist with LifeShare of the Carolinas' office in Asheville. The nonprofit provides tissues and organs for transplantation for people in southwestern North Carolina. “But now that heart means something.”
Parker has worked with donors for the last 15 years, and she's never seen the waiting list numbers go down. When she first started doing this job, there were about 30,000 people on the waiting list, and now it's nearly 108,000. The list increases by one every 12 minutes, according to Carolina Donor Services.
The situation is especially critical for kidney transplants for minorities who make up “disproportionately” high number of people on the waiting list, said Debbie Gibbs, with LifeShare in Charlotte.
It's largely because of high blood pressure and diabetes, which are more common in the African-American, Hispanic and Native American communities.
In North Carolina, 60 percent of the kidney transplant waiting list is made up of African-Americans as opposed to 35 percent nationwide. The state's donor rate for African-Americans was 26 percent in 2009.
Generally, Parker said race does not play a role in who gets an organ transplant. For any transplant, the most important factor is always blood type. But it would be best, in cases of kidney or pancreas transplants, that a person received the organ from someone who has similar tissue, she said.
“We never think that someone in our family or one of our close friends is going to need a transplant,” Wallace said. “He (Jacob) was born a completely healthy child, and some freak illness caused him to be very ill. He would have died, absolutely, at age 5 had we not gotten his transplant.”
Even now, eight years after the “nightmare” ended, the fear and worry are never far. Wallace still gets anxious when Jacob shows signs of fever.
That's something new parents Larry and Meghan Robertson understand intimately. The couple's 7-month-old baby, Ty, was born without a right kidney, and the left one is only one-third its normal size. The doctors had very little hope that he would make it. It was devastating news for the couple, who had spun so many dreams in the last nine months.
“It's not what any mother looks for when she says, ‘I'm pregnant,'” Meghan said. “I didn't think about my baby being in NICU (neonatal intensive care unit) and going through all this.”
While families everywhere were waiting for Santa, Meghan spent last Christmas Eve in a Winston-Salem hospital praying that her baby would make it through the night.
But what a difference a few months makes. With the help of a dialysis machine, 7-month-old Ty has shown strength of will that makes his parents hopeful that he will hold on long enough to get on the national organ transplant waiting list.
It's hard to tell how long the wait will be for Ty once he gets on the list. He needs to weigh 22 pounds before that happens. But the Robertsons' family and friends are hoping to speed the process along by getting tested to see if there is a match.
“I want to see him grow up,” Meghan said. “I want to see him go to school. Go to college. Get married and have my grandbabies. I want to see all that, and I hope that he is more than able to do it.”
Source
4 vets positive for hepatitis after St. Louis clinic visit
ST. LOUIS — Four veterans treated at the St. Louis VA Medical Center's dental clinic have tested positive for hepatitis, but further testing is needed to determine if inadequately sterilized dental equipment is to blame.
The Veterans Administration provided test results on Friday to The Associated Press.
The VA last month sent letters to 1,812 veterans treated at the clinic from Feb. 1, 2009, through March 11, 2010, urging them to take blood tests because the cleaning errors could have exposed them to hepatitis B, hepatitis C or HIV.
The VA says the risk of infection is remote.
The VA says 1,022 veterans have been tested and notified of results. Of those, two tested positive for hepatitis B, two tested positive for hepatitis C, and none tested positive for HIV.
Copyright 2010 The Associated Press.
Source
Also See:
The Veterans Administration provided test results on Friday to The Associated Press.
The VA last month sent letters to 1,812 veterans treated at the clinic from Feb. 1, 2009, through March 11, 2010, urging them to take blood tests because the cleaning errors could have exposed them to hepatitis B, hepatitis C or HIV.
The VA says the risk of infection is remote.
The VA says 1,022 veterans have been tested and notified of results. Of those, two tested positive for hepatitis B, two tested positive for hepatitis C, and none tested positive for HIV.
Copyright 2010 The Associated Press.
Source
Also See:
July 29, 2010
ANA598 Demonstrates SVR12 in 100% of First Group of HCV Patients Randomized to Stop All Treatment at Week 24
Benefit of ANA598 Post Therapy with IFN/RBV Persists in 6 of 6 Patients
Company to Review Data During Q2 Financial Results Call at 8:30 AM EDT Today
SAN DIEGO, July 29 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced that six of six patients (100%) in the ANA598 200 mg twice daily (bid) arm who were randomized to stop all treatment at Week 24 in an ongoing Phase II trial maintained undetectable levels of virus 12 weeks after stopping treatment, referred to as Sustained Virological Response 12, or SVR12.
The Company also reported that all available patients from the ANA598 200 mg arm who were previously reported to have undetectable levels of virus at Week 24 and continued on pegylated interferon and ribavirin (current standard of care, or SOC) also maintained undetectable levels of virus at Week 36. In addition, all patients from the ANA598 400 mg arm who were previously reported to have undetectable levels of virus at Week 12 and continued on SOC maintained undetectable levels of virus at Week 24. ANA598, Anadys' direct-acting antiviral or DAA, is being developed to treat hepatitis C and is in an ongoing Phase II trial in combination with pegylated interferon and ribavirin.
"The SVR12 data reported today for ANA598 are highly encouraging," said Steve Worland, Ph.D., President and CEO of Anadys. "These data illustrate the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy. We believe these data, coupled with the excellent barrier to resistance demonstrated in this trial as well as the favorable safety and tolerability, confirm ANA598's position as one of the most attractive agents in Phase II HCV development today."
The six patients who stopped all treatment at Week 24 were part of an investigation of response-guided treatment duration for ANA598 in which patients who had achieved undetectable levels of virus (<15 IU/mL) at Weeks 4 and 12 were randomized 1:1 to stop all treatment at Week 24 or Week 48. In addition to the six patients who stopped treatment at Week 24, six patients in the 200 mg bid arm are continuing to receive SOC alone through Week 48 for comparison purposes. Additionally, 14 patients from the ANA598 400 mg bid arm and 4 patients from the control arm (receiving placebo plus SOC) met the stopping criteria and have been randomized to stop all treatment at Week 24 or 48. The initial post-treatment results from these latter arms are expected later this year for those patients who stopped therapy at Week 24.
Conference Call Webcast and Slides
Anadys will hold a conference call and webcast today, Thursday, July 29, 2010 at 8:30 a.m. Eastern Daylight Time to discuss the post-treatment results from the ongoing Phase II combination study and Anadys' second quarter 2010 financial results A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com. A telephone replay with slides will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 28631163. The webcast and telephone replay will be available through August 12, 2010.
Phase II Combination Study
In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg bid or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.
About ANA598
ANA598, a direct-acting antiviral or DAA, is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys. In an ongoing Phase II study in which HCV patients received ANA598 at 200 mg bid or 400 mg bid in combination with interferon and ribavirin for twelve weeks, both dose levels showed comparable cEVR rates of 73-75% and a favorable safety profile. In a previous Phase I study, ANA598 demonstrated potent antiviral activity, including median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in a three day monotherapy study in treatment-naïve genotype 1 patients. ANA598 has also demonstrated a very favorable resistance profile.
Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey. The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.
Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with other anti-HCV agents currently in development that act through diverse mechanisms. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease inhibitors, polymerase inhibitors, NS5A inhibitors and cyclophilin inhibitors. In vitro combination treatment at clinically relevant concentrations of ANA598 with interferon-alpha as well as DAAs from multiple classes results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.
ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) ANA598's initial SVR12 profile based on the results from the six patients in this first group; (ii) the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy; (iii) the belief that ANA598 is one of the most attractive agents in Phase II HCV development today; (iv) the expected timing for post-treatment results from the other dose groups; and (v) the ability for patients to achieve an SVR in the Phase II combination study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues or will continue to have favorable results as the Phase II trial progresses. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2009, Form 10-Q for the quarter ended March 31, 2010 and Form 8-K filed on May 26, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
RELATED LINKS
http://www.anadyspharma.com/
Source
Company to Review Data During Q2 Financial Results Call at 8:30 AM EDT Today
SAN DIEGO, July 29 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced that six of six patients (100%) in the ANA598 200 mg twice daily (bid) arm who were randomized to stop all treatment at Week 24 in an ongoing Phase II trial maintained undetectable levels of virus 12 weeks after stopping treatment, referred to as Sustained Virological Response 12, or SVR12.
The Company also reported that all available patients from the ANA598 200 mg arm who were previously reported to have undetectable levels of virus at Week 24 and continued on pegylated interferon and ribavirin (current standard of care, or SOC) also maintained undetectable levels of virus at Week 36. In addition, all patients from the ANA598 400 mg arm who were previously reported to have undetectable levels of virus at Week 12 and continued on SOC maintained undetectable levels of virus at Week 24. ANA598, Anadys' direct-acting antiviral or DAA, is being developed to treat hepatitis C and is in an ongoing Phase II trial in combination with pegylated interferon and ribavirin.
"The SVR12 data reported today for ANA598 are highly encouraging," said Steve Worland, Ph.D., President and CEO of Anadys. "These data illustrate the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy. We believe these data, coupled with the excellent barrier to resistance demonstrated in this trial as well as the favorable safety and tolerability, confirm ANA598's position as one of the most attractive agents in Phase II HCV development today."
The six patients who stopped all treatment at Week 24 were part of an investigation of response-guided treatment duration for ANA598 in which patients who had achieved undetectable levels of virus (<15 IU/mL) at Weeks 4 and 12 were randomized 1:1 to stop all treatment at Week 24 or Week 48. In addition to the six patients who stopped treatment at Week 24, six patients in the 200 mg bid arm are continuing to receive SOC alone through Week 48 for comparison purposes. Additionally, 14 patients from the ANA598 400 mg bid arm and 4 patients from the control arm (receiving placebo plus SOC) met the stopping criteria and have been randomized to stop all treatment at Week 24 or 48. The initial post-treatment results from these latter arms are expected later this year for those patients who stopped therapy at Week 24.
Conference Call Webcast and Slides
Anadys will hold a conference call and webcast today, Thursday, July 29, 2010 at 8:30 a.m. Eastern Daylight Time to discuss the post-treatment results from the ongoing Phase II combination study and Anadys' second quarter 2010 financial results A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com. A telephone replay with slides will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 28631163. The webcast and telephone replay will be available through August 12, 2010.
Phase II Combination Study
In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg bid or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.
About ANA598
ANA598, a direct-acting antiviral or DAA, is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys. In an ongoing Phase II study in which HCV patients received ANA598 at 200 mg bid or 400 mg bid in combination with interferon and ribavirin for twelve weeks, both dose levels showed comparable cEVR rates of 73-75% and a favorable safety profile. In a previous Phase I study, ANA598 demonstrated potent antiviral activity, including median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in a three day monotherapy study in treatment-naïve genotype 1 patients. ANA598 has also demonstrated a very favorable resistance profile.
Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey. The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.
Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with other anti-HCV agents currently in development that act through diverse mechanisms. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease inhibitors, polymerase inhibitors, NS5A inhibitors and cyclophilin inhibitors. In vitro combination treatment at clinically relevant concentrations of ANA598 with interferon-alpha as well as DAAs from multiple classes results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.
ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) ANA598's initial SVR12 profile based on the results from the six patients in this first group; (ii) the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy; (iii) the belief that ANA598 is one of the most attractive agents in Phase II HCV development today; (iv) the expected timing for post-treatment results from the other dose groups; and (v) the ability for patients to achieve an SVR in the Phase II combination study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues or will continue to have favorable results as the Phase II trial progresses. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2009, Form 10-Q for the quarter ended March 31, 2010 and Form 8-K filed on May 26, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
RELATED LINKS
http://www.anadyspharma.com/
Source
On the street, you can see the harm caused by drug laws
By David Bratzer, Citizen Special July 29, 2010
Like many other police officers, I have witnessed the tragedy of the HIV epidemic first hand. It is one thing to read the statistics demonstrating the connection between illicit drug use and HIV; it is another matter entirely to patrol the streets, day in and day out, repeatedly arresting men and women infected with the HIV virus.
Our country has one of the finest health-care systems in the world, but our laws surrounding drug use result in unnecessary disease and death.
In this context, the recent announcement of the Vienna Declaration has bolstered my conviction that drug prohibition is a national policy failure.
The document, inspired by an international team of leading health scientists and academic physicians, is the official declaration of this month's International AIDS Conference in Vienna. It presents an important scientific fact that I see reflected in my work every day: "The criminalization of illicit drug users is fuelling the HIV epidemic and has resulted in overwhelmingly negative health and social consequences."
The declaration calls for a "full policy reorientation." This should not be misconstrued as an endorsement of drug use. It is simply a recognition that drug law enforcement is not an effective deterrent, citing studies showing "there is no evidence that increasing the ferocity of law enforcement meaningfully reduces the prevalence of drug use."
It is also a recognition that drug law enforcement is contributing directly to the HIV epidemic. In most parts of the world, approximately one in three HIV infections can be traced back to intravenous drug use. Toronto, Ottawa, Surrey, Winnipeg and other Canadian cities are not immune.
Drug prohibition increases the rate of HIV infections. When illegal drugs are sold through the black market, the only concern is making money. There is no financial incentive for traffickers to provide drug education, counselling or harm reduction services such as sterile needles.
In addition, in parts of Canada it is common for an injection drug user to be arrested for a minor drug charge and end up with a court-imposed condition to abstain from possessing drug paraphernalia. Addicts are then forced to choose whether to carry sterile needles and risk a new criminal charge, or to share a needle with another addict who may already have a blood-borne disease.
The Vienna Declaration is particularly important within Canada. Bill S-10 is before Parliament. It is the federal government's third attempt in as many years to create mandatory minimum sentences for certain drug offences.
The wording of this legislation virtually guarantees that street-level drug addicts will find themselves going to jail for lengthy prison terms. This will do nothing but channel limited tax dollars away from health and education and into costly incarceration policies which will turn petty drug users into hardened criminals.
HIV prevention efforts will be hampered if this bill passes. The HIV infection rates in federal prisons are similar to some African countries, according to the statistics provided by the Correctional Service of Canada. So, for many of these addicts, part of their sentence will include a substantial risk of contracting HIV or Hepatitis C.
Of course, the Vienna Declaration is not the first time a major initiative has been announced to coincide with the biannual International AIDS Conference. Ten years ago, the Durban Declaration stated a basic scientific truth: that HIV is the cause of AIDS. More than 5,000 scientists and medical doctors signed the document in an effort to confront AIDS denialism.
The main critic of the Durban Declaration was Thabo Mbeki, who was president of South Africa at the time. He believed, mistakenly, that there was a causal link between poverty and AIDS. In fact it is HIV that causes AIDS. His denials, rooted in ignorance and willful blindness, have cost many lives in South Africa.
Given this history, it will be interesting to see who opposes the Vienna Declaration. Police lobby groups have traditionally been the most vocal critics of drug policy reform. In this instance, however, they should choose their responses carefully. At stake is the very credibility of these organizations. They risk being remembered in the same light as President Mbeki, for it is clear that the new AIDS denialism is the failure to acknowledge the realities of HIV transmission.
The Vienna Declaration will play a significant role in HIV policy, and I am proud to have signed the document online at viennadeclaration.com.
I can only hope that my colleagues in law enforcement will be inspired to do the same.
David Bratzer is a member of the board of directors for Law Enforcement Against Prohibition and a police officer in British Columbia. The opinions expressed in this column do not represent the views of his employer.
© Copyright (c) The Ottawa Citizen
Source
Like many other police officers, I have witnessed the tragedy of the HIV epidemic first hand. It is one thing to read the statistics demonstrating the connection between illicit drug use and HIV; it is another matter entirely to patrol the streets, day in and day out, repeatedly arresting men and women infected with the HIV virus.
Our country has one of the finest health-care systems in the world, but our laws surrounding drug use result in unnecessary disease and death.
In this context, the recent announcement of the Vienna Declaration has bolstered my conviction that drug prohibition is a national policy failure.
The document, inspired by an international team of leading health scientists and academic physicians, is the official declaration of this month's International AIDS Conference in Vienna. It presents an important scientific fact that I see reflected in my work every day: "The criminalization of illicit drug users is fuelling the HIV epidemic and has resulted in overwhelmingly negative health and social consequences."
The declaration calls for a "full policy reorientation." This should not be misconstrued as an endorsement of drug use. It is simply a recognition that drug law enforcement is not an effective deterrent, citing studies showing "there is no evidence that increasing the ferocity of law enforcement meaningfully reduces the prevalence of drug use."
It is also a recognition that drug law enforcement is contributing directly to the HIV epidemic. In most parts of the world, approximately one in three HIV infections can be traced back to intravenous drug use. Toronto, Ottawa, Surrey, Winnipeg and other Canadian cities are not immune.
Drug prohibition increases the rate of HIV infections. When illegal drugs are sold through the black market, the only concern is making money. There is no financial incentive for traffickers to provide drug education, counselling or harm reduction services such as sterile needles.
In addition, in parts of Canada it is common for an injection drug user to be arrested for a minor drug charge and end up with a court-imposed condition to abstain from possessing drug paraphernalia. Addicts are then forced to choose whether to carry sterile needles and risk a new criminal charge, or to share a needle with another addict who may already have a blood-borne disease.
The Vienna Declaration is particularly important within Canada. Bill S-10 is before Parliament. It is the federal government's third attempt in as many years to create mandatory minimum sentences for certain drug offences.
The wording of this legislation virtually guarantees that street-level drug addicts will find themselves going to jail for lengthy prison terms. This will do nothing but channel limited tax dollars away from health and education and into costly incarceration policies which will turn petty drug users into hardened criminals.
HIV prevention efforts will be hampered if this bill passes. The HIV infection rates in federal prisons are similar to some African countries, according to the statistics provided by the Correctional Service of Canada. So, for many of these addicts, part of their sentence will include a substantial risk of contracting HIV or Hepatitis C.
Of course, the Vienna Declaration is not the first time a major initiative has been announced to coincide with the biannual International AIDS Conference. Ten years ago, the Durban Declaration stated a basic scientific truth: that HIV is the cause of AIDS. More than 5,000 scientists and medical doctors signed the document in an effort to confront AIDS denialism.
The main critic of the Durban Declaration was Thabo Mbeki, who was president of South Africa at the time. He believed, mistakenly, that there was a causal link between poverty and AIDS. In fact it is HIV that causes AIDS. His denials, rooted in ignorance and willful blindness, have cost many lives in South Africa.
Given this history, it will be interesting to see who opposes the Vienna Declaration. Police lobby groups have traditionally been the most vocal critics of drug policy reform. In this instance, however, they should choose their responses carefully. At stake is the very credibility of these organizations. They risk being remembered in the same light as President Mbeki, for it is clear that the new AIDS denialism is the failure to acknowledge the realities of HIV transmission.
The Vienna Declaration will play a significant role in HIV policy, and I am proud to have signed the document online at viennadeclaration.com.
I can only hope that my colleagues in law enforcement will be inspired to do the same.
David Bratzer is a member of the board of directors for Law Enforcement Against Prohibition and a police officer in British Columbia. The opinions expressed in this column do not represent the views of his employer.
© Copyright (c) The Ottawa Citizen
Source
RNA Offers a Safer Way to Reprogram Cells
MIT researchers used RNA to induce these fibroblast cells to express four genes necessary to reprogram cells to an immature state. (Credit: Yanik Laboratory, MIT)
ScienceDaily (July 29, 2010) — In recent years, scientists have shown that they can reprogram human skin cells to an immature state that allows the cells to become any type of cell. This ability, known as pluripotency, holds the promise of treating diseases such as diabetes and Parkinson's disease by transforming the patients' own cells into replacements for the nonfunctioning tissue.
However, the techniques now used to transform cells pose some serious safety hazards. To deliver the genes necessary to reprogram cells to a pluripotent state, scientists use viruses carrying DNA, which then becomes integrated into the cell's own DNA. But this so-called DNA-based reprogramming carries the risk of disrupting the cell's genome and leading it to become cancerous.
Now, for the first time, MIT researchers have shown that they can deliver those same reprogramming genes using RNA, the genetic material that normally ferries instructions from DNA to the cell's protein-making machinery. This method could prove much safer than DNA-based reprogramming, say the researchers, Associate Professor of Electrical and Biological Engineering Mehmet Fatih Yanik and electrical engineering graduate student Matthew Angel.
Yanik and Angel describe the method, also the subject of Angel's master's thesis, in the July 23 issue of the journal PLoS ONE.
However, the researchers say they cannot yet claim to have reprogrammed the cells into a pluripotent state. To prove that, they would need to grow the cells in the lab for a longer period of time and study their ability to develop into other cell types -- a process now underway in their lab. Their key achievement is demonstrating that the genes necessary for reprogramming can be delivered with RNA.
"Before this, nobody had a way to transfect cells multiple times with protein-encoding RNA," says Yanik. (Transfection is the process of introducing DNA or RNA into a cell without using viruses to deliver them.)
In 2006, researchers at Kyoto University showed they could reprogram mouse skin cells into a pluripotent, embryonic-like state with just four genes. More recently, other scientists have achieved the same result in human cells by delivering the proteins encoded by those genes directly into mature cells, but that process is more expensive, inefficient and time-consuming than reprogramming with DNA.
Yanik and Angel decided to pursue a new alternative by transfecting cells with messenger RNA (mRNA), a short-lived molecule that carries genetic instructions copied from DNA.
However, they found that RNA transfection poses a significant challenge: When added to mature human skin cells, mRNA provokes an immune response meant to defend against viruses made of RNA. Repeated exposure to long strands of RNA leads cells to undergo cell suicide, sacrificing themselves to help prevent the rest of the body from being infected.
Yanik and Angel knew that some RNA viruses, including hepatitis C, can successfully suppress that defensive response. After reviewing studies of hepatitis C's evasive mechanisms, they did experiments showing they could shut off the response by delivering short interfering RNA (siRNA) that blocks production of several proteins key to the response.
Once the defense mechanism is shut off, mRNA carrying the genes for cell reprogramming can be safely delivered. The researchers showed that they could induce cells to produce the reprogramming proteins for more than a week, by delivering siRNA and mRNA every other day.
Source
Also See: RNA offers a safer way to reprogram cells
Greater Risk Of Diabetes Found In Hepatitis C Patients
By Steven Marsh • Jul 28th, 2010 • Category: Blood Sugar, Health News, Health Resources News
Patients who have been diagnosed with hepatitis C may be more susceptible to developing type 2 diabetes, according to a study published in the journal Gastroenterology.
A blood-born disease, hepatitis C spreads through unprotected sexual intercourse or the use of injection drugs and causes liver damage. If people don’t receive treatments for this disease, they can suffer from liver cancer or failure of the organ, resulting in death.
During the study, a team of investigators monitored a total of 29 patients with hepatitis C who showed signs of insulin resistance, a symptom of diabetes.
The results of the trial showed that 15 of the participants experienced insulin complications in their muscle tissue compared to the liver. The inability to properly absorb the sugar created high levels of the nutrient in the blood, which could lead to developing diabetes.
"At this stage, it is helpful for people with hepatitis C to understand insulin resistance and what it can mean for them," said Don Chisholm, co-author of the study. He added that "if they have relatives with type 2 diabetes, they will be genetically prone to developing it themselves and so would be advised to manage their diets very carefully and take plenty of exercise – to slow onset."
As of 2007, an estimated 17,000 new cases of hepatitis C are diagnosed in the U.S. each year, according to the Centers for Disease Control and Prevention.
Source
Bid To Aid Transplant Cancer Patients
Article Date: 29 Jul 2010 - 1:00 PDT
Organ transplant patients who develop cancer may be helped by a treatment that uses blood cells to attack their tumour.
University of Edinburgh researchers have generated a bank of white blood cells from healthy blood donors to treat patients with a blood cancer called post transplant lymphoproliferative disease (PTLD).
The study found that patients treated with these blood cells - called 'killer' T cells - remained free from the cancer for up to nine years following treatment.
PTLD is associated with Epstein-Barr virus (EBV), a herpes virus that is carried by more than 90 per cent of the population and better known for causing glandular fever.
In most individuals the virus does not cause any illness but it can cause tumours in transplant patients.
This is because their immune systems are heavily suppressed to prevent rejection of the transplanted organ.
Up to 10 per cent of transplant patients may develop the cancer in the first few years following transplant and around 50 per cent of those will die even with standard treatment.
T cells are a type of white blood cell that patrol the body identifying and killing virus infected cells.
A team at the University of Edinburgh's Centre for Infectious Diseases grew T cells in the laboratory and gave them to PTLD patients for one month.
The T cells were programmed to find and kill the virus-infected tumour cells to reduce or eradicate the tumour.
A total of 33 PTLD patients who had not responded to standard treatments were treated in a Cancer Research UK-funded trial.
Around half the treated patients showed a good response after six months.
This latest study shows that 90 per cent of those who responded initially have remained cancer free for between four and nine years.
The long term survival rate was significantly better in the six month responder group compared to the six month non-responder group.
"Our results are very encouraging and show that not only are our cells effective in the short term but that they can also induce a long term remission of PTLD in patients with more unmanageable disease."
said Dr Tanzina Haque, Lead researcher, now of Royal Free Hospital, UCL Medical School.
The Edinburgh researchers in conjunction with the Scottish National Blood Transfusion Service have obtained translational funding from the Wellcome Trust to make a new bank of 'killer' T cells that will become available for use on a not-for-profit basis in the next few years.
The research is published in the journal Transplantation.
Source:
University of Edinburgh
Source
Organ transplant patients who develop cancer may be helped by a treatment that uses blood cells to attack their tumour.
University of Edinburgh researchers have generated a bank of white blood cells from healthy blood donors to treat patients with a blood cancer called post transplant lymphoproliferative disease (PTLD).
The study found that patients treated with these blood cells - called 'killer' T cells - remained free from the cancer for up to nine years following treatment.
PTLD is associated with Epstein-Barr virus (EBV), a herpes virus that is carried by more than 90 per cent of the population and better known for causing glandular fever.
In most individuals the virus does not cause any illness but it can cause tumours in transplant patients.
This is because their immune systems are heavily suppressed to prevent rejection of the transplanted organ.
Up to 10 per cent of transplant patients may develop the cancer in the first few years following transplant and around 50 per cent of those will die even with standard treatment.
T cells are a type of white blood cell that patrol the body identifying and killing virus infected cells.
A team at the University of Edinburgh's Centre for Infectious Diseases grew T cells in the laboratory and gave them to PTLD patients for one month.
The T cells were programmed to find and kill the virus-infected tumour cells to reduce or eradicate the tumour.
A total of 33 PTLD patients who had not responded to standard treatments were treated in a Cancer Research UK-funded trial.
Around half the treated patients showed a good response after six months.
This latest study shows that 90 per cent of those who responded initially have remained cancer free for between four and nine years.
The long term survival rate was significantly better in the six month responder group compared to the six month non-responder group.
"Our results are very encouraging and show that not only are our cells effective in the short term but that they can also induce a long term remission of PTLD in patients with more unmanageable disease."
said Dr Tanzina Haque, Lead researcher, now of Royal Free Hospital, UCL Medical School.
The Edinburgh researchers in conjunction with the Scottish National Blood Transfusion Service have obtained translational funding from the Wellcome Trust to make a new bank of 'killer' T cells that will become available for use on a not-for-profit basis in the next few years.
The research is published in the journal Transplantation.
Source:
University of Edinburgh
Source
Hepatitis C retreatment offers hope if initial one fails
by paige varner pvarner@post-dispatch.com 314-340-8018
Posted: Thursday, July 29, 2010 12:00 am
For the 40 percent to 50 percent of patients who aren't cured of hepatitis C after their initial treatment, Dr. Bruce R. Bacon of St. Louis University and his team of researchers have increased the chances of a cure upon re-treatment.
About 11 percent of the 515 people retreated in Bacon's trials were cured using the Food and Drug Administration-approved medication combination, Infergen with an antiviral pill.
Of those with milder strains of hepatitis C, about 35 percent in the trials were cured.
In the first round of treatment, patients are given weekly shots of an alpha interferon — in larger amounts than that which the body normally makes to fight pathogens — along with the antiviral pill ribavirin.
This combination cures 50 percent to 60 percent of cases, but others can start another round, this time injecting the interferon medicine Infergen daily, along with taking the ribavirin, for up to 48 weeks.
Bacon, who holds the endowed chair in gastroenterology at SLU School of Medicine, and his team published their findings last summer after researching from 2004 to 2006.
For those with the virus who feel the 11 percent cure rate in the second round isn't high enough, Bacon said they will still have hepatitis C if they don't at least try re-treatment.
Another concern about the medicine combination is the side effects, which are similar to the flulike symptoms the virus already causes, such as fatigue, anemia, troubled breathing, irritability.
"But more than the side effects, you don't want to have hepatitis C," Bacon said.
Interferon and ribavirin are the only treatments for hepatitis C, which inflames the liver and after many years can lead to cirrhosis, or liver scarring, in 20 percent to 30 percent of patients.
Those with the virus can prevent cirrhosis development by not drinking excessive amounts of alcohol.
Some won't know they have the virus. Bacon said the flulike symptoms can set in gradually, making them feel sick for decades before they are diagnosed.
Contracting hepatitis C requires a blood-to-blood transmission, and Bacon said most cases have a history of one of three things:
• A blood transfusion before 1992.
• Sharing needles or illicit drugs — "even teenagers at a party who did something stupid," Bacon said
• Working in the health care field. Paramedics, physicians and nurses come into contact with blood daily. Just one needle stick could cause hepatitis C.
Acute cases of the virus can clear on their own. Infergen with ribavirin is FDA-approved in chronic cases, or for people who have had the virus for at least six months.
Infergen cannot be taken by anyone under 18 years old or with compensated liver disease due to cirrhosis complications.
Source
Posted: Thursday, July 29, 2010 12:00 am
For the 40 percent to 50 percent of patients who aren't cured of hepatitis C after their initial treatment, Dr. Bruce R. Bacon of St. Louis University and his team of researchers have increased the chances of a cure upon re-treatment.
About 11 percent of the 515 people retreated in Bacon's trials were cured using the Food and Drug Administration-approved medication combination, Infergen with an antiviral pill.
Of those with milder strains of hepatitis C, about 35 percent in the trials were cured.
In the first round of treatment, patients are given weekly shots of an alpha interferon — in larger amounts than that which the body normally makes to fight pathogens — along with the antiviral pill ribavirin.
This combination cures 50 percent to 60 percent of cases, but others can start another round, this time injecting the interferon medicine Infergen daily, along with taking the ribavirin, for up to 48 weeks.
Bacon, who holds the endowed chair in gastroenterology at SLU School of Medicine, and his team published their findings last summer after researching from 2004 to 2006.
For those with the virus who feel the 11 percent cure rate in the second round isn't high enough, Bacon said they will still have hepatitis C if they don't at least try re-treatment.
Another concern about the medicine combination is the side effects, which are similar to the flulike symptoms the virus already causes, such as fatigue, anemia, troubled breathing, irritability.
"But more than the side effects, you don't want to have hepatitis C," Bacon said.
Interferon and ribavirin are the only treatments for hepatitis C, which inflames the liver and after many years can lead to cirrhosis, or liver scarring, in 20 percent to 30 percent of patients.
Those with the virus can prevent cirrhosis development by not drinking excessive amounts of alcohol.
Some won't know they have the virus. Bacon said the flulike symptoms can set in gradually, making them feel sick for decades before they are diagnosed.
Contracting hepatitis C requires a blood-to-blood transmission, and Bacon said most cases have a history of one of three things:
• A blood transfusion before 1992.
• Sharing needles or illicit drugs — "even teenagers at a party who did something stupid," Bacon said
• Working in the health care field. Paramedics, physicians and nurses come into contact with blood daily. Just one needle stick could cause hepatitis C.
Acute cases of the virus can clear on their own. Infergen with ribavirin is FDA-approved in chronic cases, or for people who have had the virus for at least six months.
Infergen cannot be taken by anyone under 18 years old or with compensated liver disease due to cirrhosis complications.
Source
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