Alimentary Pharmacology & Therapeutics
Early View (Articles online in advance of print)
S. M. Martinez 1, G. Fernández-Varo 2, P. González 1, E. Sampson 3, M. Bruguera 1, M. Navasa 1, W. Jiménez 2, J. M. Sánchez-Tapias 1, X. Forns 1
Article first published online: 26 OCT 2010
DOI: 10.1111/j.1365-2036.2010.04500.x
© 2010 Blackwell Publishing Ltd
Author Information
1 Liver Unit, Hospital Clinic, IDIBAPS and Ciberehd, Barcelona, Spain.
2 Department of Biochemistry and Molecular Genetics, Hospital Clinic, IDIBAPS and Ciberehd, Barcelona, Spain.
3 Siemens Healthcare Diagnostics, Tarrytown, NY, USA.
*Correspondence: Dr X. Forns, Liver Unit, Hospital Clinic, IDIBAPS and Ciberehd, Villarroel 170, Barcelona 08036, Spain. E-mail: xforns@clinic.ub.es
Abstract
Summary
Background Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C.
Aim To validate and compare the diagnostic performance of non-invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment.
Methods The performances of Forns’ score, AST to platelet ratio index (APRI), FIB-4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients.
Results Forns’ score, APRI, FIB-4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB-4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non-1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR.
Conclusions Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.
Source
December 4, 2010
Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial
Alimentary Pharmacology & Therapeutics
Early View (Articles online in advance of print)
N. D. Freedman 1, T. M. Curto 2, C. Morishima 3, L. B. Seeff 4, Z. D. Goodman 5, E. C. Wright 6, R. Sinha 1, J. E. Everhart 7, the HALT-C Trial Group 1
Article first published online: 2 NOV 2010
DOI: 10.1111/j.1365-2036.2010.04503.x
Published 2010. This article is a US Government work and is in the public domain in the USA.
Author Information
1 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
2 New England Research Institutes, Watertown, MA, USA.
3 Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
4 Division of Digestive Diseases and Nutrition, and Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
5 Division of Hepatic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
6 Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
7 Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
* Correspondence: Dr N. D. Freedman, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS/320, MSC 7232, Rockville, MD 20852, USA. E-mail: freedmanne@mail.nih.gov
Abstract
Summary
Background Silymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear.
Aim To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment.
Methods Patients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.
Results At baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P < 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33–1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes.
Conclusions Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).
Source
Early View (Articles online in advance of print)
N. D. Freedman 1, T. M. Curto 2, C. Morishima 3, L. B. Seeff 4, Z. D. Goodman 5, E. C. Wright 6, R. Sinha 1, J. E. Everhart 7, the HALT-C Trial Group 1
Article first published online: 2 NOV 2010
DOI: 10.1111/j.1365-2036.2010.04503.x
Published 2010. This article is a US Government work and is in the public domain in the USA.
Author Information
1 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
2 New England Research Institutes, Watertown, MA, USA.
3 Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
4 Division of Digestive Diseases and Nutrition, and Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
5 Division of Hepatic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
6 Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
7 Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
* Correspondence: Dr N. D. Freedman, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS/320, MSC 7232, Rockville, MD 20852, USA. E-mail: freedmanne@mail.nih.gov
Abstract
Summary
Background Silymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear.
Aim To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment.
Methods Patients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.
Results At baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P < 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33–1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes.
Conclusions Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).
Source
New York City widens pool of kidney donors
NEW YORK
Wed Dec 1, 2010 11:47am EST
NEW YORK (Reuters) - New York City is changing its kidney donors program to allow organs to be recovered from people who die of heart attacks outside hospitals.
The pilot program, launched on Wednesday by New York City Mayor Michael Bloomberg and the New York Organ Donation Network, overrides rules that restrict the donation of kidneys to cardiac arrest victims who died inside hospitals.
"This new pilot program will help us test a process that could transform the way we donate organs and help save many lives," Bloomberg said in a statement.
Under the program, an Organ Preservation Team will respond to cases of cardiac arrest when an organ donor card is found, or if the deceased is a registered donor. Bodies will then be moved by ambulance to Bellevue hospital for final next-of-kin consent and the transplant operation.
"We are hopeful that it will prove to be an effective and efficient way of honoring donor wishes and making more organs available for life-saving transplants," said Health and Hospitals Corporation President and CEO Alan Aviles.
New York City Fire Commissioner Salvatore Cassano said the new program would benefit both those receiving new organs and those who wished to donate at the time of their death.
The program is funded with a $1.5 million grant from the Department of Health Resources and Services Administration. The pilot program covers Manhattan and runs until May when it will be reviewed for possible expansion.
According to city officials, nearly 8,000 New Yorkers are awaiting organ transplants. Nationally, over 109,000 are waiting for organs, a list to which a new name is added every 13 minutes. Approximately 6,500 people die each year because a transplant is not available.
(Reporting by Bernd Debusmann Jr.; Editing by Mark Egan and Jerry Norton)
Source
Wed Dec 1, 2010 11:47am EST
NEW YORK (Reuters) - New York City is changing its kidney donors program to allow organs to be recovered from people who die of heart attacks outside hospitals.
The pilot program, launched on Wednesday by New York City Mayor Michael Bloomberg and the New York Organ Donation Network, overrides rules that restrict the donation of kidneys to cardiac arrest victims who died inside hospitals.
"This new pilot program will help us test a process that could transform the way we donate organs and help save many lives," Bloomberg said in a statement.
Under the program, an Organ Preservation Team will respond to cases of cardiac arrest when an organ donor card is found, or if the deceased is a registered donor. Bodies will then be moved by ambulance to Bellevue hospital for final next-of-kin consent and the transplant operation.
"We are hopeful that it will prove to be an effective and efficient way of honoring donor wishes and making more organs available for life-saving transplants," said Health and Hospitals Corporation President and CEO Alan Aviles.
New York City Fire Commissioner Salvatore Cassano said the new program would benefit both those receiving new organs and those who wished to donate at the time of their death.
The program is funded with a $1.5 million grant from the Department of Health Resources and Services Administration. The pilot program covers Manhattan and runs until May when it will be reviewed for possible expansion.
According to city officials, nearly 8,000 New Yorkers are awaiting organ transplants. Nationally, over 109,000 are waiting for organs, a list to which a new name is added every 13 minutes. Approximately 6,500 people die each year because a transplant is not available.
(Reporting by Bernd Debusmann Jr.; Editing by Mark Egan and Jerry Norton)
Source
Anemia in Treated-HCV Patients Bodes Well for Sustained Virologic Response
NEW YORK (Reuters Health) Dec 01 - Anemia that develops in patients infected with hepatitis C virus (HCV) during treatment with peginterferon-alfa and ribavirin (PEG-IFN/RBV) may be a good sign, new research hints.
In a large study, researchers found that patients who developed anemia were more likely to achieve sustained virologic response (SVR) than those who did not, despite decreased RBV dosing following a decline in hemoglobin levels. In addition, the virologic relapse rate wasn't increased in patients who cut back on RBV dose.
These data "firmly underscore the recommendation for RBV dose reduction as the primary strategy for management of treatment-related anemia," write Dr. Mark S. Sulkowski, of Johns Hopkins University School of Medicine in Baltimore, and colleagues in the November 10th issue of Gastroenterology.
They also found that the use of erythropoiesis-stimulating agents (ESAs) minimized discontinuation of treatment in patients with early-onset anemia, leading to higher SVR rates in this subgroup.
Anemia is seen in up to 30% of treated HCV patients and often leads to RBV dose reduction and/or discontinuation of treatment, Dr. Sulkowski and colleagues note in their report.
However, because lower SVR rates have been reported in patients who cut back on RBV, "many clinicians and patients prefer to avoid this strategy and instead use ESAs (off-label) to improve anemia-related symptoms while maintaining RBV dose," the investigators note.
Nonetheless, "considerable uncertainty exists regarding the role of adjuvant ESAs during HCV treatment," they point out.
Dr. Sulkowski's team evaluated the relationship between treatment-related anemia, ESA use, and treatment outcomes in 3,023 treatment-naive patients with HCV genotype 1. All were treated for up to 48 weeks with a standard PEG-IFN/RBV regimen. ESAs were allowed for patients with hemoglobin levels less than 10 g/dL after RBV dose reduction.
Anemia occurred in 28.6% of study patients. Most of these patients lowered their RBV dose and 51.9% were given an ESA.
"Unexpectedly," the investigators say, the SVR rate was significantly higher in anemic patients than nonanemic patients (difference, +12% for anemic patients).
Moreover, SVR rates were associated with the magnitude of hemoglobin decrease. SVR rates were 43.7% in patients with an absolute hemoglobin decline greater than 3 grams per deciliter compared with 29.9% in those with a maximum decline of 3 grams per deciliter.
Patients with early-onset anemia (after 8 weeks or less of treatment) had significantly higher SVR rates with ESA use than those with later onset anemia. Those with early-onset anemia were also less apt to discontinue treatment due to adverse events (12.6% vs. 30.1%; P < 0.001).
ESAs didn't affect SVR or discontinuation rates among patients with late-onset anemia, suggesting that these patients are "not likely to benefit from adjuvant ESAs," the authors note.
The finding that RBV dose reduction wasn't associated with lower SVR rates is important, they say. "ESAs should not be used solely to avoid RBV dose reduction in anemic patients."
"Prospective, randomized controlled trials are needed to define the optimal role of adjuvant ESAs during HCV treatment regimens that include PEG-IFN/RBV," they conclude.
Gastroenterology. Posted November 10, 2010. Abstract
Source
In a large study, researchers found that patients who developed anemia were more likely to achieve sustained virologic response (SVR) than those who did not, despite decreased RBV dosing following a decline in hemoglobin levels. In addition, the virologic relapse rate wasn't increased in patients who cut back on RBV dose.
These data "firmly underscore the recommendation for RBV dose reduction as the primary strategy for management of treatment-related anemia," write Dr. Mark S. Sulkowski, of Johns Hopkins University School of Medicine in Baltimore, and colleagues in the November 10th issue of Gastroenterology.
They also found that the use of erythropoiesis-stimulating agents (ESAs) minimized discontinuation of treatment in patients with early-onset anemia, leading to higher SVR rates in this subgroup.
Anemia is seen in up to 30% of treated HCV patients and often leads to RBV dose reduction and/or discontinuation of treatment, Dr. Sulkowski and colleagues note in their report.
However, because lower SVR rates have been reported in patients who cut back on RBV, "many clinicians and patients prefer to avoid this strategy and instead use ESAs (off-label) to improve anemia-related symptoms while maintaining RBV dose," the investigators note.
Nonetheless, "considerable uncertainty exists regarding the role of adjuvant ESAs during HCV treatment," they point out.
Dr. Sulkowski's team evaluated the relationship between treatment-related anemia, ESA use, and treatment outcomes in 3,023 treatment-naive patients with HCV genotype 1. All were treated for up to 48 weeks with a standard PEG-IFN/RBV regimen. ESAs were allowed for patients with hemoglobin levels less than 10 g/dL after RBV dose reduction.
Anemia occurred in 28.6% of study patients. Most of these patients lowered their RBV dose and 51.9% were given an ESA.
"Unexpectedly," the investigators say, the SVR rate was significantly higher in anemic patients than nonanemic patients (difference, +12% for anemic patients).
Moreover, SVR rates were associated with the magnitude of hemoglobin decrease. SVR rates were 43.7% in patients with an absolute hemoglobin decline greater than 3 grams per deciliter compared with 29.9% in those with a maximum decline of 3 grams per deciliter.
Patients with early-onset anemia (after 8 weeks or less of treatment) had significantly higher SVR rates with ESA use than those with later onset anemia. Those with early-onset anemia were also less apt to discontinue treatment due to adverse events (12.6% vs. 30.1%; P < 0.001).
ESAs didn't affect SVR or discontinuation rates among patients with late-onset anemia, suggesting that these patients are "not likely to benefit from adjuvant ESAs," the authors note.
The finding that RBV dose reduction wasn't associated with lower SVR rates is important, they say. "ESAs should not be used solely to avoid RBV dose reduction in anemic patients."
"Prospective, randomized controlled trials are needed to define the optimal role of adjuvant ESAs during HCV treatment regimens that include PEG-IFN/RBV," they conclude.
Gastroenterology. Posted November 10, 2010. Abstract
Source
December 3, 2010
December 2010 B News: HBV Treatment In the News
National Strategy for the Prevention and Control of Viral Hepatitis
Dr. Howard Koh, the Assistant Secretary for Health, gave the President’s Choice Lecture at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston this month, where he spoke about the U.S. administration’s response to the Institute of Medicine (IOM) report on viral hepatitis. Dr. Koh took the initiative to convene the first viral hepatitis interagency work group to look at what is being done across all Health and Human Services (HHS) agencies for this growing epidemic. A “National Strategy for the Control of Viral Hepatitis and Liver Cancer” that builds upon the IOM report is being developed by the HHS working group and is slated for publication in early 2011. Learn more »
HBV Drug Therapy Okay for Pregnant Women
Pregnant women with active hepatitis B infection can be safely and effectively treated with telbivudine (Tyzeka), researchers reported at the 2010 annual AASLD meeting. A study involving more than 80 women found that just over half of the women given telbivudine achieved a complete virologic response right before delivery compared with none of the controls, according to Calvin Pan, MD, of Mount Sinai School of Medicine in Flushing, N.Y., and colleagues. There has been a controversy over whether pregnant women with hepatitis B should be treated, mainly due to concerns over the safety of the fetus. Learn more »
HBV Reactivation and Rituximab:
A Complex Clinical Challenge
HBV reactivation is a serious and often fatal complication of rituximab-based therapy that has led to a black box warning on the package insert. Researchers report, “The importance of HBV reactivation is two-fold. First, symptomatic hepatitis flare carries a high mortality rate, which has ranged from 5 to 40% in various reports. Second, HBV reactivation, if it occurs prior to completion of chemotherapy, will likely result in substantial delays in the delivery of potentially curative chemotherapy for the underlying malignancy…such delay is detrimental to long-term cancer-specific outcome.” Read Full Article »
From Podium to Practice:
Updates in HBV Treatment
Nov. 2 – Capsule Summaries of key oral and poster presentations from the 2010 AASLD Meeting of the American Association for the Study of Liver have been selected by leading experts in the field. Learn more »
Source
Dr. Howard Koh, the Assistant Secretary for Health, gave the President’s Choice Lecture at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston this month, where he spoke about the U.S. administration’s response to the Institute of Medicine (IOM) report on viral hepatitis. Dr. Koh took the initiative to convene the first viral hepatitis interagency work group to look at what is being done across all Health and Human Services (HHS) agencies for this growing epidemic. A “National Strategy for the Control of Viral Hepatitis and Liver Cancer” that builds upon the IOM report is being developed by the HHS working group and is slated for publication in early 2011. Learn more »
HBV Drug Therapy Okay for Pregnant Women
Pregnant women with active hepatitis B infection can be safely and effectively treated with telbivudine (Tyzeka), researchers reported at the 2010 annual AASLD meeting. A study involving more than 80 women found that just over half of the women given telbivudine achieved a complete virologic response right before delivery compared with none of the controls, according to Calvin Pan, MD, of Mount Sinai School of Medicine in Flushing, N.Y., and colleagues. There has been a controversy over whether pregnant women with hepatitis B should be treated, mainly due to concerns over the safety of the fetus. Learn more »
HBV Reactivation and Rituximab:
A Complex Clinical Challenge
HBV reactivation is a serious and often fatal complication of rituximab-based therapy that has led to a black box warning on the package insert. Researchers report, “The importance of HBV reactivation is two-fold. First, symptomatic hepatitis flare carries a high mortality rate, which has ranged from 5 to 40% in various reports. Second, HBV reactivation, if it occurs prior to completion of chemotherapy, will likely result in substantial delays in the delivery of potentially curative chemotherapy for the underlying malignancy…such delay is detrimental to long-term cancer-specific outcome.” Read Full Article »
From Podium to Practice:
Updates in HBV Treatment
Nov. 2 – Capsule Summaries of key oral and poster presentations from the 2010 AASLD Meeting of the American Association for the Study of Liver have been selected by leading experts in the field. Learn more »
Source
Infection and systemic inflammation, not ammonia, are associated with Grade III/IV hepatic encephalopathy, but not mortality in cirrhosis
Articles in Press
D.L. Shawcross 1‡, Y. Sharifi 1‡, J.B. Canavan 3, A.D. Yeoman 12, R.D. Abeles 12, N.J. Taylor 1, G. Auzinger 2, W. Bernal 12, J.A. Wendon 12
Received 19 April 2010; received in revised form 23 June 2010; accepted 14 July 2010. published online 01 December 2010.
Uncorrected Proof
Background & Aims
Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date.
Methods
We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan, 2000 and March, 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded.
Results
46% of patients had positive cultures taken within ±48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted.
Conclusions
These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.
Keywords: Hepatic encephalopathy, Cirrhosis, Inflammation, Infection, Outcomes
Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation, CRP, C-reactive protein, GCS, Glasgow Coma Score, HE, hepatic encephalopathy, HDU, High Dependency Unit, ICU, Intensive Care Unit, MELD, Model for End-stage Liver Disease, SIRS, Systemic Inflammatory Response Syndrome, SOFA, Sequential Organ Failure Assessment
1 Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, London, UK
2 Liver Intensive Therapy Unit, King’s College Hospital, Denmark Hill, London, UK
3 NIHR Comprehensive Biomedical Research Centre at Guy’s & St. Thomas’s NHS Foundation Trust and King’s College London, UK
Corresponding author. Address: Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Tel.: +44 20 3299 2316; fax: +44 20 3299 3167.
‡ These authors contributed equally to this paper.
PII: S0168-8278(10)00838-X
doi:10.1016/j.jhep.2010.07.045
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
Source
D.L. Shawcross 1‡, Y. Sharifi 1‡, J.B. Canavan 3, A.D. Yeoman 12, R.D. Abeles 12, N.J. Taylor 1, G. Auzinger 2, W. Bernal 12, J.A. Wendon 12
Received 19 April 2010; received in revised form 23 June 2010; accepted 14 July 2010. published online 01 December 2010.
Uncorrected Proof
Background & Aims
Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date.
Methods
We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan, 2000 and March, 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded.
Results
46% of patients had positive cultures taken within ±48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted.
Conclusions
These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.
Keywords: Hepatic encephalopathy, Cirrhosis, Inflammation, Infection, Outcomes
Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation, CRP, C-reactive protein, GCS, Glasgow Coma Score, HE, hepatic encephalopathy, HDU, High Dependency Unit, ICU, Intensive Care Unit, MELD, Model for End-stage Liver Disease, SIRS, Systemic Inflammatory Response Syndrome, SOFA, Sequential Organ Failure Assessment
1 Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, London, UK
2 Liver Intensive Therapy Unit, King’s College Hospital, Denmark Hill, London, UK
3 NIHR Comprehensive Biomedical Research Centre at Guy’s & St. Thomas’s NHS Foundation Trust and King’s College London, UK
Corresponding author. Address: Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Tel.: +44 20 3299 2316; fax: +44 20 3299 3167.
‡ These authors contributed equally to this paper.
PII: S0168-8278(10)00838-X
doi:10.1016/j.jhep.2010.07.045
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
Source
Arizona Cuts Financing for Transplant Patients
By MARC LACEY
Published: December 2, 2010
PHOENIX — Even physicians with decades of experience telling patients that their lives are nearing an end are having difficulty discussing a potentially fatal condition that has arisen in Arizona: Death by budget cut.
Effective at the beginning of October, Arizona stopped financing certain transplant operations under the state’s version of Medicaid. Many doctors say the decision amounts to a death sentence for some low-income patients, who have little chance of survival without transplants and lack the hundreds of thousands of dollars needed to pay for them.
“The most difficult discussions are those that involve patients who had been on the donor list for a year or more and now we have to tell them they’re not on the list anymore,” said Dr. Rainer Gruessner, a transplant specialist at the University of Arizona College of Medicine. “The frustration is tremendous. It’s more than frustration.”
Organ transplants are already the subject of a web of regulations, which do not guarantee that everyone in need of a life-saving organ will receive one. But Arizona’s transplant specialists are alarmed that patients who were in line to receive transplants one day were, after the state’s budget cuts to its Medicaid program, ruled ineligible the next — unless they raised the money themselves.
Francisco Felix, 32, a father of four who has hepatitis C and is in need of a liver, received news a few weeks ago that a family friend was dying and wanted to donate her liver to him. But the budget cuts meant he no longer qualified for a state-financed transplant.
He was prepared anyway at Banner Good Samaritan Medical Center as his relatives scrambled to raise the needed $200,000. When the money did not come through, the liver went to someone else on the transplant list.
“I know times are tight and cuts are needed, but you can’t cut human lives,” said Mr. Felix’s wife, Flor. “You just can’t do that.”
Such high drama is unfolding regularly here as more and more of the roughly 100 people affected by the cuts are becoming known: the father of six who died before receiving a bone marrow transplant, the plumber in need of a new heart and the high school basketball coach who struggles to breathe during games at high altitudes as she awaits a lung transplant.
“I appreciate the need for budget restraints,” said Dr. Andrew M. Yeager, a University of Arizona professor who is director of the Blood and Marrow Transplantation Program at the Arizona Cancer Center. “But when one looks at a potentially lifesaving treatment, admittedly expensive, and we have data to support efficacy, cuts like this are shortsighted and sad.”
State Medicaid officials said they recommended discontinuing some transplants only after assessing the success rates for previous patients. Among the discontinued procedures are lung transplants, liver transplants for hepatitis C patients and some bone marrow and pancreas transplants, which altogether would save the state about $4.5 million a year.
“As an agency, we understand there have been difficult cuts and there will have to be more difficult cuts looking forward,” said Jennifer Carusetta, chief legislative liaison at the state Medicaid agency.
The issue has led to a fierce political battle, with Democrats condemning the reductions as “Brewercare,” after Gov. Jan Brewer.
“We made it very clear at the time of the vote that this was a death sentence,” said State Senator Leah Landrum Taylor, a Democrat. “This is not a luxury item. We’re not talking about cosmetic surgery.”
The Republican governor has in turn blamed “Obamacare,” meaning the federal health care overhaul, for the transplant cuts even though the Arizona vote came in March, before President Obama signed that bill into law.
But a top Republican, State Representative John Kavanagh, has already pledged to reconsider at least some of the state’s cuts for transplants when the Legislature reconvenes in January. Mr. Kavanagh, chairman of the Appropriations Committee, said he does not believe lawmakers had the full picture of the effect of the cuts on patients when they voted.
“It’s difficult to be linked to a situation where people’s lives are jeopardized and turned upside down,” he said in an interview. “Thankfully no one has died as a result of this, and I believe we have time to rectify this.”
Across the country, states have restricted benefits to their Medicaid programs, according to a 50-state survey published in September by the Kaiser Commission on Medicaid and the Uninsured. But none have gone as far as Arizona in eliminating some transplants, which are considered optional services under federal law.
Before the Legislature acted, Arizona’s Medicaid agency had provided an analysis to lawmakers of the transplants that were cut, which many health experts now say was seriously flawed. For instance, the state said that 13 of 14 patients under the state’s health system who received bone marrow transplants from nonrelatives over a two-year period died within six months.
But outside specialists said the success rates were considerably higher, particularly for leukemia patients in their first remission.
“Something needs to be done,” said Dr. Emmanuel Katsanis, a bone marrow transplant expert at the University of Arizona. “There’s no doubt that people aren’t going to make it because of this decision. What do you tell someone? You need a transplant but you have to raise the money?”
Just before the Oct. 1 deadline, Mark Price, a father of six who was fighting leukemia, learned he needed a bone marrow transplant. But his doctor, Jeffrey R. Schriber, found donor matches for his transplant the very day the new rules went into effect, and Mr. Price no longer qualified for coverage by the Arizona Health Care Cost Containment System, the formal name for the state’s Medicaid program.
What happened next was at once inspirational and heart-rending.
Out of the blue, an anonymous financial donor quickly stepped forward and agreed to cover the hundreds of thousands of dollars needed for Mr. Price’s surgery. But Mr. Price died last weekend, after his cancer returned before the operation could be done. He was buried on Thursday, next to his grandfather.
“It’s not correct to say that he died as a result of the cuts,” said Dr. Schriber, who is active in lobbying for the financing to be restored. “Did it prey on his mind? Did it make his last days more difficult? No doubt.”
Elsewhere, the fund-raising is already under way.
Mr. Felix and others are now trying to raise enough for new organs through NTAF, a nonprofit organization based in Pennsylvania formerly known as the National Transplant Assistance Fund that helps transplant patients pay for their medical costs. National coverage of their plight has already led to more than $100,000 in donations for some of the patients affected by the budget cuts. The Felix family is also planning a yard sale this weekend so he does not lose the chance to get another liver.
There has been a flurry of lobbying to persuade the state to reverse the decision. Dr. Gruessner said he and others met with state health officials recently to propose other cuts associated with transplants, like eliminating tests typically conducted before surgery.
If the Legislature does decide to reconsider the cuts, one of the affected people, a plumber and father of three named Randy Shepherd, 36, who has an ailing heart and needs a transplant, plans to attend the debate.
“I’m trying not to take it personally,” he said of being cut out of the program. “None of the politicians had heard of me when they made their decision. They didn’t say, ‘Let’s kill this guy.’ ”
Source
Published: December 2, 2010
PHOENIX — Even physicians with decades of experience telling patients that their lives are nearing an end are having difficulty discussing a potentially fatal condition that has arisen in Arizona: Death by budget cut.
Effective at the beginning of October, Arizona stopped financing certain transplant operations under the state’s version of Medicaid. Many doctors say the decision amounts to a death sentence for some low-income patients, who have little chance of survival without transplants and lack the hundreds of thousands of dollars needed to pay for them.
“The most difficult discussions are those that involve patients who had been on the donor list for a year or more and now we have to tell them they’re not on the list anymore,” said Dr. Rainer Gruessner, a transplant specialist at the University of Arizona College of Medicine. “The frustration is tremendous. It’s more than frustration.”
Organ transplants are already the subject of a web of regulations, which do not guarantee that everyone in need of a life-saving organ will receive one. But Arizona’s transplant specialists are alarmed that patients who were in line to receive transplants one day were, after the state’s budget cuts to its Medicaid program, ruled ineligible the next — unless they raised the money themselves.
Francisco Felix, 32, a father of four who has hepatitis C and is in need of a liver, received news a few weeks ago that a family friend was dying and wanted to donate her liver to him. But the budget cuts meant he no longer qualified for a state-financed transplant.
He was prepared anyway at Banner Good Samaritan Medical Center as his relatives scrambled to raise the needed $200,000. When the money did not come through, the liver went to someone else on the transplant list.
“I know times are tight and cuts are needed, but you can’t cut human lives,” said Mr. Felix’s wife, Flor. “You just can’t do that.”
Such high drama is unfolding regularly here as more and more of the roughly 100 people affected by the cuts are becoming known: the father of six who died before receiving a bone marrow transplant, the plumber in need of a new heart and the high school basketball coach who struggles to breathe during games at high altitudes as she awaits a lung transplant.
“I appreciate the need for budget restraints,” said Dr. Andrew M. Yeager, a University of Arizona professor who is director of the Blood and Marrow Transplantation Program at the Arizona Cancer Center. “But when one looks at a potentially lifesaving treatment, admittedly expensive, and we have data to support efficacy, cuts like this are shortsighted and sad.”
State Medicaid officials said they recommended discontinuing some transplants only after assessing the success rates for previous patients. Among the discontinued procedures are lung transplants, liver transplants for hepatitis C patients and some bone marrow and pancreas transplants, which altogether would save the state about $4.5 million a year.
“As an agency, we understand there have been difficult cuts and there will have to be more difficult cuts looking forward,” said Jennifer Carusetta, chief legislative liaison at the state Medicaid agency.
The issue has led to a fierce political battle, with Democrats condemning the reductions as “Brewercare,” after Gov. Jan Brewer.
“We made it very clear at the time of the vote that this was a death sentence,” said State Senator Leah Landrum Taylor, a Democrat. “This is not a luxury item. We’re not talking about cosmetic surgery.”
The Republican governor has in turn blamed “Obamacare,” meaning the federal health care overhaul, for the transplant cuts even though the Arizona vote came in March, before President Obama signed that bill into law.
But a top Republican, State Representative John Kavanagh, has already pledged to reconsider at least some of the state’s cuts for transplants when the Legislature reconvenes in January. Mr. Kavanagh, chairman of the Appropriations Committee, said he does not believe lawmakers had the full picture of the effect of the cuts on patients when they voted.
“It’s difficult to be linked to a situation where people’s lives are jeopardized and turned upside down,” he said in an interview. “Thankfully no one has died as a result of this, and I believe we have time to rectify this.”
Across the country, states have restricted benefits to their Medicaid programs, according to a 50-state survey published in September by the Kaiser Commission on Medicaid and the Uninsured. But none have gone as far as Arizona in eliminating some transplants, which are considered optional services under federal law.
Before the Legislature acted, Arizona’s Medicaid agency had provided an analysis to lawmakers of the transplants that were cut, which many health experts now say was seriously flawed. For instance, the state said that 13 of 14 patients under the state’s health system who received bone marrow transplants from nonrelatives over a two-year period died within six months.
But outside specialists said the success rates were considerably higher, particularly for leukemia patients in their first remission.
“Something needs to be done,” said Dr. Emmanuel Katsanis, a bone marrow transplant expert at the University of Arizona. “There’s no doubt that people aren’t going to make it because of this decision. What do you tell someone? You need a transplant but you have to raise the money?”
Just before the Oct. 1 deadline, Mark Price, a father of six who was fighting leukemia, learned he needed a bone marrow transplant. But his doctor, Jeffrey R. Schriber, found donor matches for his transplant the very day the new rules went into effect, and Mr. Price no longer qualified for coverage by the Arizona Health Care Cost Containment System, the formal name for the state’s Medicaid program.
What happened next was at once inspirational and heart-rending.
Out of the blue, an anonymous financial donor quickly stepped forward and agreed to cover the hundreds of thousands of dollars needed for Mr. Price’s surgery. But Mr. Price died last weekend, after his cancer returned before the operation could be done. He was buried on Thursday, next to his grandfather.
“It’s not correct to say that he died as a result of the cuts,” said Dr. Schriber, who is active in lobbying for the financing to be restored. “Did it prey on his mind? Did it make his last days more difficult? No doubt.”
Elsewhere, the fund-raising is already under way.
Mr. Felix and others are now trying to raise enough for new organs through NTAF, a nonprofit organization based in Pennsylvania formerly known as the National Transplant Assistance Fund that helps transplant patients pay for their medical costs. National coverage of their plight has already led to more than $100,000 in donations for some of the patients affected by the budget cuts. The Felix family is also planning a yard sale this weekend so he does not lose the chance to get another liver.
There has been a flurry of lobbying to persuade the state to reverse the decision. Dr. Gruessner said he and others met with state health officials recently to propose other cuts associated with transplants, like eliminating tests typically conducted before surgery.
If the Legislature does decide to reconsider the cuts, one of the affected people, a plumber and father of three named Randy Shepherd, 36, who has an ailing heart and needs a transplant, plans to attend the debate.
“I’m trying not to take it personally,” he said of being cut out of the program. “None of the politicians had heard of me when they made their decision. They didn’t say, ‘Let’s kill this guy.’ ”
Source
Manifestations of Chronic Hepatitis C Virus Infection Beyond the Liver
Clinical Gastroenterology and Hepatology
Volume 8, Issue 12 , Pages 1017-1029, December 2010
Ira M. Jacobson , Patrice Cacoub, Luigino Dal Maso, Stephen A. Harrison, Zobair M. Younossi
Abstract
In addition to its effects in the liver, chronic hepatitis C virus (HCV) infection can have serious consequences for other organ systems. Extrahepatic manifestations include mixed cryoglobulinemia (MC) vasculitis, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis–like polyarthritis, and autoantibody production; reductions in quality of life involve fatigue, depression, and cognitive impairment. MC vasculitis, certain types of lymphoma, insulin resistance, and cognitive function appear to respond to anti-HCV therapy. However, treatments for HCV and other biopsychosocial factors can reduce quality of life and complicate management. HCV treatment has a high overall cost that increases when extrahepatic manifestations are considered. HCV appears to have a role in the pathogenesis of MC vasculitis, certain types of lymphoma, and insulin resistance. Clinicians who treat patients with HCV infections should be aware of potential extrahepatic manifestations and how these can impact and alter management of their patients.
Keywords: Hepatitis C Virus, Burden of Disease, Extrahepatic Comorbidities, Health-Related Quality of Life, Epidemiology
Source
Volume 8, Issue 12 , Pages 1017-1029, December 2010
Ira M. Jacobson , Patrice Cacoub, Luigino Dal Maso, Stephen A. Harrison, Zobair M. Younossi
Abstract
In addition to its effects in the liver, chronic hepatitis C virus (HCV) infection can have serious consequences for other organ systems. Extrahepatic manifestations include mixed cryoglobulinemia (MC) vasculitis, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis–like polyarthritis, and autoantibody production; reductions in quality of life involve fatigue, depression, and cognitive impairment. MC vasculitis, certain types of lymphoma, insulin resistance, and cognitive function appear to respond to anti-HCV therapy. However, treatments for HCV and other biopsychosocial factors can reduce quality of life and complicate management. HCV treatment has a high overall cost that increases when extrahepatic manifestations are considered. HCV appears to have a role in the pathogenesis of MC vasculitis, certain types of lymphoma, and insulin resistance. Clinicians who treat patients with HCV infections should be aware of potential extrahepatic manifestations and how these can impact and alter management of their patients.
Keywords: Hepatitis C Virus, Burden of Disease, Extrahepatic Comorbidities, Health-Related Quality of Life, Epidemiology
Source
Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C
Transplant International
Volume 24, Issue 1, pages 43–50, January 2011
DOI: 10.1111/j.1432-2277.2010.01141.x
Davide Bitetto 1, Carlo Fabris 1, Ezio Fornasiere 1, Corrado Pipan 2, Elisa Fumolo 1, Annarosa Cussigh 1, Sara Bignulin 1, Sara Cmet 1, Elisabetta Fontanini 1, Edmondo Falleti 1, Romina Martinella 2, Mario Pirisi 3,4, Pierluigi Toniutto 1
Author Information
1 Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
2 Hygiene and Epidemiology, University of Udine, Udine, Italy
3 Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
4 Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
*Correspondence: Pierluigi Toniutto MD, DPMSC, Internal Medicine, Medical Liver Transplantation Unit, University of Udine, 33100 Udine, Italy. Tel.: +390432559801; fax: +39043242097; e-mail: pierluigi.toniutto@uniud.it
Abstract
Keywords: interferon; liver transplantation; recurrent hepatitis C; vitamin D
Summary
In immune-competent patients, higher vitamin D levels predicted sustained viral response (SVR) following interferon (INF) and ribavirin therapy for chronic hepatitis C. This study aimed to verify the influence of vitamin D serum levels and/or vitamin D supplementation in predicting SVR rates for recurrent hepatitis C (RHC). Forty-two consecutive patients were treated for RHC with combination therapy with INF-α and ribavirin for 48 weeks. Vitamin D serum levels were measured in all patients before antiviral therapy. In 15 patients oral vitamin D3 supplementation was administered to avoid further bone loss. SVR was observed in 13 patients; it was achieved in 1/10 severely vitamin D deficient (≤10 ng/ml) patients, in 6/20 deficient (>10 and ≤20 ng/ml) and in 6/12 with near normal (>20 ng/ml) 25-OH vitamin D serum levels (P < 0.05). Cholecalciferol supplementation, in the presence of a normal or near normal baseline vitamin D concentration, (improvement of chi-square P < 0.05, odds ratio 2.22) and possessing a genotype other than 1 (improvement of chi-square P < 0.05, odds ratio 3.383) were the only variables independently associated to SVR. In conclusion, vitamin D deficiency predicts an unfavourable response to antiviral treatment of RHC. Vitamin D supplementation improves the probability of achieving a SVR following antiviral treatment.
Source
Volume 24, Issue 1, pages 43–50, January 2011
DOI: 10.1111/j.1432-2277.2010.01141.x
Davide Bitetto 1, Carlo Fabris 1, Ezio Fornasiere 1, Corrado Pipan 2, Elisa Fumolo 1, Annarosa Cussigh 1, Sara Bignulin 1, Sara Cmet 1, Elisabetta Fontanini 1, Edmondo Falleti 1, Romina Martinella 2, Mario Pirisi 3,4, Pierluigi Toniutto 1
Author Information
1 Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
2 Hygiene and Epidemiology, University of Udine, Udine, Italy
3 Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
4 Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
*Correspondence: Pierluigi Toniutto MD, DPMSC, Internal Medicine, Medical Liver Transplantation Unit, University of Udine, 33100 Udine, Italy. Tel.: +390432559801; fax: +39043242097; e-mail: pierluigi.toniutto@uniud.it
Abstract
Keywords: interferon; liver transplantation; recurrent hepatitis C; vitamin D
Summary
In immune-competent patients, higher vitamin D levels predicted sustained viral response (SVR) following interferon (INF) and ribavirin therapy for chronic hepatitis C. This study aimed to verify the influence of vitamin D serum levels and/or vitamin D supplementation in predicting SVR rates for recurrent hepatitis C (RHC). Forty-two consecutive patients were treated for RHC with combination therapy with INF-α and ribavirin for 48 weeks. Vitamin D serum levels were measured in all patients before antiviral therapy. In 15 patients oral vitamin D3 supplementation was administered to avoid further bone loss. SVR was observed in 13 patients; it was achieved in 1/10 severely vitamin D deficient (≤10 ng/ml) patients, in 6/20 deficient (>10 and ≤20 ng/ml) and in 6/12 with near normal (>20 ng/ml) 25-OH vitamin D serum levels (P < 0.05). Cholecalciferol supplementation, in the presence of a normal or near normal baseline vitamin D concentration, (improvement of chi-square P < 0.05, odds ratio 2.22) and possessing a genotype other than 1 (improvement of chi-square P < 0.05, odds ratio 3.383) were the only variables independently associated to SVR. In conclusion, vitamin D deficiency predicts an unfavourable response to antiviral treatment of RHC. Vitamin D supplementation improves the probability of achieving a SVR following antiviral treatment.
Source
Approval of rapid INSTI[TM] HIV-1 Antibody Test
On November 29, 2010, the Food and Drug Administration (FDA) announced the approval of the INSTI™ HIV-1 Antibody Test, a new, single use rapid test for the detection of antibodies to Human Immunodeficiency Virus Type 1 (HIV-1) in human venipuncture whole blood, fingerstick blood, or plasma specimens. The newly approved test provides results in as little as 60 seconds, in contrast to the six previously approved rapid HIV tests, which typically deliver results in about 10 - 20 minutes.
Rapid HIV tests allow people to learn their HIV status in a single visit to a testing site, instead of returning days later for results, dramatically increasing the number of people who ultimately learn their serostatus after taking an HIV test.
Rapid testing also helps increase access to HIV testing because testing can be performed outside of the traditional laboratory setting. Individuals who undergo testing can be counseled immediately concerning their HIV status and, if they are positive, given the opportunity to enter medical care.
The INSTI™ HIV-1 Antibody Test can be used in clinical laboratories, in public health laboratories and in point-of-care settings. The test is classified as Moderate Complexity under CLIA (Clinical Laboratory Improvements Amendments).
It is highly sensitive [The overall sensitivity for the different sample types: 99.8% (95% CI = 99.3% - 99.9%) in fingerstick whole blood, 99.9% (95% CI = 99.5% - 100%) in venipuncture whole blood, 99.9% (95% CI = 99.5% - 100%) in plasma] and specific [The overall specificity for the different samples types: 99.5% (95% CI = 99.0% - 99.8) in fingerstick whole blood, 100% (95% CI = 99.7% - 100%) in venipuncture whole blood, 100% (95% CI = 99.7% - 100%) in plasma] for the detection of antibodies to HIV-1.
The assay is not intended to be used for screening of blood donors.
The INSTI™ HIV-1 Antibody Test is manufactured by bioLytical Laboratories Inc., Richmond, BC, Canada.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Source
Rapid HIV tests allow people to learn their HIV status in a single visit to a testing site, instead of returning days later for results, dramatically increasing the number of people who ultimately learn their serostatus after taking an HIV test.
Rapid testing also helps increase access to HIV testing because testing can be performed outside of the traditional laboratory setting. Individuals who undergo testing can be counseled immediately concerning their HIV status and, if they are positive, given the opportunity to enter medical care.
The INSTI™ HIV-1 Antibody Test can be used in clinical laboratories, in public health laboratories and in point-of-care settings. The test is classified as Moderate Complexity under CLIA (Clinical Laboratory Improvements Amendments).
It is highly sensitive [The overall sensitivity for the different sample types: 99.8% (95% CI = 99.3% - 99.9%) in fingerstick whole blood, 99.9% (95% CI = 99.5% - 100%) in venipuncture whole blood, 99.9% (95% CI = 99.5% - 100%) in plasma] and specific [The overall specificity for the different samples types: 99.5% (95% CI = 99.0% - 99.8) in fingerstick whole blood, 100% (95% CI = 99.7% - 100%) in venipuncture whole blood, 100% (95% CI = 99.7% - 100%) in plasma] for the detection of antibodies to HIV-1.
The assay is not intended to be used for screening of blood donors.
The INSTI™ HIV-1 Antibody Test is manufactured by bioLytical Laboratories Inc., Richmond, BC, Canada.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Source
December 2, 2010
Peregrine Pharmaceuticals initiates phase I/II trial for HCC
Dec 02, 2010 (Datamonitor via COMTEX) --
Peregrine Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company engaged in development of monoclonal antibody-based drugs, has initiated an investigator-sponsored trial, or IST, for patients with advanced hepatocellular carcinoma, or HCC, or liver cancer.
This phase I/II trial will treat patients with Peregrine's investigational monoclonal antibody bavituximab in combination with sorafenib.
Currently, Peregrine's bavituximab is being evaluated in combination with chemotherapy in multiple phase II trials in non-small cell lung cancer and advanced breast cancer, as well as a phase Ib trial for hepatitis C virus (HCV) and HIV coinfection.
"In prior studies, bavituximab has demonstrated broad therapeutic potential in multiple oncology indications," said Marvin R. Garovoy, M.D., head of clinical science at Peregrine Pharmaceuticals. "Our IST program is designed to provide valuable clinical data on bavituximab's potential use in different therapeutic combinations and indications. We also expect to further clarify details of bavituximab's multiple mechanisms of action, and to identify specific biomarkers that could ultimately help to measure and predict bavituximab's potential anti-tumor and immunostimulatory effects. We look forward to collaborating with Dr Yopp and his team, as well as other investigators who have applied for our program."
Source
Peregrine Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company engaged in development of monoclonal antibody-based drugs, has initiated an investigator-sponsored trial, or IST, for patients with advanced hepatocellular carcinoma, or HCC, or liver cancer.
This phase I/II trial will treat patients with Peregrine's investigational monoclonal antibody bavituximab in combination with sorafenib.
Currently, Peregrine's bavituximab is being evaluated in combination with chemotherapy in multiple phase II trials in non-small cell lung cancer and advanced breast cancer, as well as a phase Ib trial for hepatitis C virus (HCV) and HIV coinfection.
"In prior studies, bavituximab has demonstrated broad therapeutic potential in multiple oncology indications," said Marvin R. Garovoy, M.D., head of clinical science at Peregrine Pharmaceuticals. "Our IST program is designed to provide valuable clinical data on bavituximab's potential use in different therapeutic combinations and indications. We also expect to further clarify details of bavituximab's multiple mechanisms of action, and to identify specific biomarkers that could ultimately help to measure and predict bavituximab's potential anti-tumor and immunostimulatory effects. We look forward to collaborating with Dr Yopp and his team, as well as other investigators who have applied for our program."
Source
The Journey East
Tuesday, 30 November 2010 13:10 Sean Foley
Santa Cruz local walks cross-country to raise awareness for Hepatitis C
In the age of freeways and airplanes, transportation is fast and efficient, if not a little dehumanizing. We live in a time in which most people hop in their cars to run even the smallest errand. But this winter, one Santa Cruz resident is ditching his car and hitting the road for a transcontinental trip—on foot.
Meet Joseph Melsha. On Friday, Nov. 26, the Santa Cruz native embarked on a journey that will take him through the United States, with nothing more than a bag stocked with basic amenities (a tent, flashlight, and a small camp stove) on his back and a sturdy pair of walking shoes on his feet. He has plotted a course that will take him to his final destination in Boston, Mass.
Melsha isn’t walking across the United States merely for fun; he’s putting his feet to use to raise awareness throughout the country about a harmful disease, Hepatitis C. Melsha lost his mother to Hepatitis C in 2005. His sister, who lives in Boston, currently lives with the condition, and Melsha’s venture through the country will ultimately lead him to her.
“Walking is the easy part,” Melsha says. “I’ve been walking since I was a year old.” However, walking across the country at the onset of winter is another story. The brutal Midwestern winter prevented Melsha from taking a linear route across the country. Instead, he will tread southward towards Santa Monica and then follow Route 66 through the southwest. He plans to eventually end up in Jacksonville, Fla. before making the final trek up north to Boston.
Melsha decided to walk to Boston to raise awareness on a whim. “In this economy, it’s hard to find work,” he says. “I just felt like I wanted to do something positive with my time … and then I decided I need to see my sister … I just decided, ‘I’m walking to Boston! See everyone in a few months!’”
He decided to make his journey to see his sister an effort that would galvanize the public and spread knowledge about Hepatitis C. Hepatitis C is a disease caused from the Hepatitis C virus. It infects the liver and can lead to cirrhosis, liver cancer, and other permanent or long-term liver damage, according to WebMD. The virus gets spread through contact with infected blood. The Center for Disease Control (CDC) reports that approximately 3.2 million people in the United States live with chronic Hepatitis C.
Spreading awareness by walking will be more effective than by travelling through the country by other means because “it takes longer, and it’s a big deal,” says Melsha. “Everybody wonders, ‘So what, Hep. C?’ and then ‘What’s Hep. C?’ and I’ve already raised a tremendous amount of awareness and I haven’t even started walking yet.”
Just days before he set off, Melsha told Good Times that he was encouraged by the attention he had already received from fellow Santa Cruzans. “Everywhere I go people are like, ‘Oh, hey you’re Joe Melsha.’ These are people I’ve never seen before, at places like the grocery store,” he says.
In addition, Melsha has received a lot of electronic support. “Every morning I have over 200 emails with people sharing their stories,” he says. “I wake up crying basically. They’re saying such nice things. Already this has exceeded my expectations.” His visibility can in part be measured through the popularity of his Facebook page, which now receives a barrage of friend requests daily.
As he walks, Melsha will periodically update his fans and followers with photo and video updates on his Facebook page as well as on his personal website, joemelsha.com. These updates will occur whenever he has access to a computer. (“It’s all very informal,” he says.) He plans on walking 10 to 12 hours a day for as long as it takes for him to reach Boston. Although he hasn’t been training at a gym (“I’ve been training by eating Twinkies and staying on my feet … trying to gain a little weight before the journey,” he quips), Melsha feels that he could make it to Boston in as little as 100 days. He estimates the walk will actually take him about six months to complete.
As he walks and educates those he meets, Melsha hopes to inspire others to find a cause they are passionate about. He says, “I want to show people [that] you can do something with your life … You don’t have to be anyone, I’m just Joe Melsha, and I’m just walking.”
Source
December 1, 2010
Necrolytic acral erythema
Dermatology Online Journal
Volume 16 Number 11
November 2010
Utpal Patel MD PhD, Aaron Loyd MD, Rishi Patel MD, Shane Meehan MD, Roopal Kundu MD
Dermatology Online Journal 16 (11): 15
Department of Dermatology, New York University, New York, New York
Abstract
Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection and closely related to a group of necrolytic erythemas and metabolic syndromes. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. Based on morphology and histopathologic features, NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. The condition is particularly important for clinicians to diagnose because the majority of the patients present to dermatologists without a known history of HCV infection. Thus, NAE can serve as a cutaneous marker for underlying HCV infection. Resolution of NAE can be achieved by treatment of the underlying HCV infection and the use of oral zinc therapy.
History
A 53-year-old woman presented to the Charles C. Harris Skin and Cancer Pavilion with a scaly, lichenified, pruritic eruption over the dorsal aspects of the feet and ankles for approximately one year. A diagnosis of eczematous dermatitis initially was made, and she was treated with triamcinolone 0.1 percent ointment and urea cream. This treatment led to resolution of the pruritus; however, there was minimal improvement of the cutaneous lesions. A biopsy was performed, and patch tests to the North American Standard Series and shoe series were negative. Review of systems was not contributory.
Past medical history included dermatomyositis that was treated with intravenous immunoglobin, hepatitis C virus infection treated with ribavarin and INF-α, cataracts, and iron-deficiency anemia. The patient was treated with zinc sulfate 220 mg twice daily. There was partial resolution of the plaques over three months of treatment.
Physical examination
Symmetric, sharply-demarcated, hyperkeratotic, violaceous, hyperpigmented, lichenified plaques were present on the dorsal aspects of the feet and extended to the toes and over the Achilles tendons.
Laboratory data
A comprehensive metabolic profile, complete blood count, thyroid function tests, amylase, lipase, and zinc levels were normal. Hepatitis C virus RNA count was measured at 11.5 x 106 IU/mL, and the genotype was determined to be type IA. Ultrasound and a computed tomography scan of the abdomen showed no evidence of cirrhosis, portal hypertension, or hepatocellular carcinoma.
Histopathology
There is a superficial, perivascular inflammatory infiltrate comprised predominantly of lymphocytes. Some lymphocytes extend to a hyperplastic epidermis where there are spongiosis and foci of sharply demarcated parakeratosis. There is slight pallor of the superficial epidermis.
Comment
Necrolytic acral erythema (NAE) is a recently recognized dermatosis, which is almost exclusively associated with hepatitis C virus infection and is closely related to a group of necrolytic erythemas and metabolic syndromes. It was first described in 1996 in Egyptian patients with hepatitis C virus (HCV) infection [1]. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. The average patient age is 40 years (range from 11 to 76 years) and there is no sex predilection [2]. Since the initial report, over 70 cases have been described worldwide, including Pakistan, India, United States, and Taiwan, but the vast majority of reports have come from Egypt [3-18]. The disproportionate regional distribution is likely due to several factors: 1. The worldwide prevalence of HCV infection is 3 percent, whereas in Egypt it is estimated to be 15 to 20 percent. 2. There are differences in the HCV genotype. 3. There is likely a lack of clinical awareness of the condition among physicians [12, 14, 19]. NAE is particularly important for clinicians to diagnose because the majority of patients present to dermatologists without a known history of HCV infection [12, 14] Thus, NAE can serve as a cutaneous marker for underlying HCV infection.
Based on a longitudinal study, NAE develops in three stages, with variable degrees of pruritus and/or burning [14]. The initial stage is characterized by scaly, dusky papules with an erythematous rim. The lesion then progresses to the fully-developed, erythematous-to-violaceous, lichenified, scaly plaque. In the third stage, the lesion progressively thins and exhibits increased hyperpigmentation. The most common sites of involvement are the dorsal aspects of the feet, over the Achilles tendons, malleoli, legs, and knees. Less frequent sites of involvement include the elbows, hands, buttocks, and genitalia. There is sparing of the palms, soles, face, and mucous membranes [12]. Histopathologic features include a non-specific psoriasiform pattern [5, 14, 17], acanthosis, papillomatosis, and hyper- and parakeratosis, with necrotic keratinocytes in the superficial epidermis. NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. However, these entities can be distinguished based on clinical and laboratory evaluation [8].
Although a number of mechanisms have been proposed for NAE, there is insufficient evidence to support a precise pathogenesis. The most consistent finding associated with NAE is HCV infection. In fact, there are only four reported cases of NAE without associated HCV infection [3, 4, 8]. Furthermore, two of three studies have observed a correlation between the severity of HCV infection (based on liver enzymes) and the severity of NAE [1, 13, 14]. Additional support comes from cases in which treatment of HCV with ribavarin and INF-α has lead to resolution of NAE [1, 14, 16]. The mechanism by which HCV infection causes NAE is not clear. Attempts to demonstrate HCV viral particles in the involved skin with electron microscopy (for viral particles) or with real time polymerase chain reaction (for HCV RNA) have been unsuccessful [12]. NAE may arise secondary to HCV viral antigen-induced humoral and/or cell-mediated autoimmune responses to viral and/or endogenous cutaneous antigens. Yet another possibility is the development of metabolic abnormalities secondary to hepatocellular dysfunction from HCV infection, which leads to cutaneous manifestations [20, 21].
The next most consistent finding associated with NAE is zinc deficiency, which may result from HCV infection. There are a number of studies that demonstrate decreased zinc levels in patients with NAE [11, 13]. When patients with laboratory evidence of zinc deficiency are treated with zinc (at doses ranging from 60 mg to 440 mg per day), clinical improvement has been noted that ranges from mild to complete resolution [1, 7, 9, 11, 12, 13, 18]. The most consistent improvement is noted at the dose of 440 mg per day. Even in patients with normal serum zinc levels, zinc supplementation has lead to clinical improvement of NAE. It is thought that zinc deficiency may occur in the skin prior to the development of clinical zinc deficiency as assessed by serum zinc levels [22].
Other metabolic conditions that are less clearly associated with NAE are hypoalbuminemia, which is possibly due to the role of albumin as a carrier for essential nutrients that include zinc; hypoaminoacidemia, which is secondary to depletion of epidermal protein and which may increase susceptibility of keratinocytes to necrolysis; and elevated glucagon levels, which are thought to cause elevated levels of pro-inflammatory arachidonic acid and its metabolites [1, 13, 16, 18, 23, 24]. Some authors argue that NAE is a variant of necrolytic migratory erythema (NME) based on the similarity of the clinical and histopathologic features and the proposed pathologic mechanisms, such as hypoalbuminemia and zinc deficiency [13]. The main features that differentiate NAE from NME are the strong association of NAE with HCV infection and the typical localization of NAE to the dorsal aspects of the feet.
Treatment for NAE is not well defined. Because the majority of patients with NAE present without a prior diagnosis of HCV infection, it is imperative to determine HCV infection status in any patient suspected to have NAE. If an infection is identified, the HCV disease severity should be assessed and a treatment plan devised with a hepatologist. An evaluation should be carried out to identify and treat the underlying metabolic deficiency. Zinc therapy (440 mg per day) should be attempted, even in patients with normal serum zinc levels because the probability of benefit outweighs the minimal risk of therapy. There is a single case report that shows improvement with the use of tacrolimus ointment, which may be attempted [6].
References
1. el Darouti M, Abu el Ela M. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252
2. Geria AN, et al. Necrolytic acral erythema: a review of the literature. Cutis 2009; 83:309
3. Nikam BP. Necrolytic acral erythema seronegative for hepatitis C virus - two cases from India treated with oral zinc. Int J Dermatol 2009; 48:1096
4. Wu YH, et al. Necrolytic acral erythema without hepatitis C infection. J Cutan Pathol 2009; 36:355
5. Bentley D, et al. Lack of classic histology should not prevent diagnosis of necrolytic acral erythema. J Am Acad Dermatol 2009; 60:504
6. Manzur A, Siddiqui AH. Necrolytic acral erythema: successful treatment with topical tacrolimus ointment. Int J Dermatol 2008; 47:1073
7. de Carvalho Fantini B, et al. Necrolytic acral erythema successfully treated with oral zinc. Int J Dermatol 2008; 47:872
8. Liu A, et al. Necrolytic acral erythema: a case not associated with hepatitis C infection. Dermatol Online J 2008; 14:10
9. Najarian DJ, et al. Hypozincemia and hyperzincuria associated with necrolytic acral erythema. Int J Dermatol 2008; 47:709
10. Fielder LM, et al. Necrolytic acral erythema: case report and review of the literature. Cutis 2008; 81:355
11. Najarian DJ, et al. Zinc deficiency associated with necrolytic acral erythema. J Am Acad Dermatol 2006; 55:S108
12. El-Ghandour TM, et al. Necrolytic acral erythema in Egyptian patients with hepatitis C virus infection. J Gastroenterol Hepatol 2006; 21:1200
13. Nofal, AA, et al. Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity? Int J Dermatol 2005; 44:916
14. Abdallah MA, et al. Necrolytic acral erythema: a cutaneous sign of hepatitis C virus infection. J Am Acad Dermatol 2005; 53:247
15. Abdallah MA, et al. Necrolytic acral erythema: a patient from the United States successfully treated with oral zinc. Arch Dermatol 2005; 141:85
16. Hivnor CM, et al. Necrolytic acral erythema: response to combination therapy with interferon and ribavirin. J Am Acad Dermatol 2004; 50:S12
17. Abdallah MA, et al. Histological study of necrolytic acral erythema. J Ark Med Soc 2004; 100:354
18. Khanna VJ, et al. Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc. Arch Dermatol 2000; 136:755
19. Frank C, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 2000; 355:887
20. Mason AL, et al. Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 1999; 29:328
21. Hadziyannis SJ. Skin diseases associated with hepatitis C virus infection. J Eur Acad Dermatol Venereol 1998; 10:12
22. Delaporte E, et al. Necrolytic migratory erythema-like eruption in zinc deficiency associated with alcoholic liver disease. Br J Dermatol 1997; 137:1027
23. Jenkins DK, et al. Effects of albumin on fatty acid, protein, eicosanoid levels in rat mesenteric arterial bed perfusions. Can J Physiol Pharmacol. 1998; 66:679
24. Marinkovich MP, et al. Necrolytic migratory erythema without glucagonoma in patients with liver disease. J Am Acad Dermatol 1995; 32:604
Source
Volume 16 Number 11
November 2010
Utpal Patel MD PhD, Aaron Loyd MD, Rishi Patel MD, Shane Meehan MD, Roopal Kundu MD
Dermatology Online Journal 16 (11): 15
Department of Dermatology, New York University, New York, New York
Abstract
Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection and closely related to a group of necrolytic erythemas and metabolic syndromes. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. Based on morphology and histopathologic features, NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. The condition is particularly important for clinicians to diagnose because the majority of the patients present to dermatologists without a known history of HCV infection. Thus, NAE can serve as a cutaneous marker for underlying HCV infection. Resolution of NAE can be achieved by treatment of the underlying HCV infection and the use of oral zinc therapy.
History
Figure 1
Figure 2
Past medical history included dermatomyositis that was treated with intravenous immunoglobin, hepatitis C virus infection treated with ribavarin and INF-α, cataracts, and iron-deficiency anemia. The patient was treated with zinc sulfate 220 mg twice daily. There was partial resolution of the plaques over three months of treatment.
Physical examination
Symmetric, sharply-demarcated, hyperkeratotic, violaceous, hyperpigmented, lichenified plaques were present on the dorsal aspects of the feet and extended to the toes and over the Achilles tendons.
Laboratory data
A comprehensive metabolic profile, complete blood count, thyroid function tests, amylase, lipase, and zinc levels were normal. Hepatitis C virus RNA count was measured at 11.5 x 106 IU/mL, and the genotype was determined to be type IA. Ultrasound and a computed tomography scan of the abdomen showed no evidence of cirrhosis, portal hypertension, or hepatocellular carcinoma.
Histopathology
There is a superficial, perivascular inflammatory infiltrate comprised predominantly of lymphocytes. Some lymphocytes extend to a hyperplastic epidermis where there are spongiosis and foci of sharply demarcated parakeratosis. There is slight pallor of the superficial epidermis.
Comment
Necrolytic acral erythema (NAE) is a recently recognized dermatosis, which is almost exclusively associated with hepatitis C virus infection and is closely related to a group of necrolytic erythemas and metabolic syndromes. It was first described in 1996 in Egyptian patients with hepatitis C virus (HCV) infection [1]. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. The average patient age is 40 years (range from 11 to 76 years) and there is no sex predilection [2]. Since the initial report, over 70 cases have been described worldwide, including Pakistan, India, United States, and Taiwan, but the vast majority of reports have come from Egypt [3-18]. The disproportionate regional distribution is likely due to several factors: 1. The worldwide prevalence of HCV infection is 3 percent, whereas in Egypt it is estimated to be 15 to 20 percent. 2. There are differences in the HCV genotype. 3. There is likely a lack of clinical awareness of the condition among physicians [12, 14, 19]. NAE is particularly important for clinicians to diagnose because the majority of patients present to dermatologists without a known history of HCV infection [12, 14] Thus, NAE can serve as a cutaneous marker for underlying HCV infection.
Based on a longitudinal study, NAE develops in three stages, with variable degrees of pruritus and/or burning [14]. The initial stage is characterized by scaly, dusky papules with an erythematous rim. The lesion then progresses to the fully-developed, erythematous-to-violaceous, lichenified, scaly plaque. In the third stage, the lesion progressively thins and exhibits increased hyperpigmentation. The most common sites of involvement are the dorsal aspects of the feet, over the Achilles tendons, malleoli, legs, and knees. Less frequent sites of involvement include the elbows, hands, buttocks, and genitalia. There is sparing of the palms, soles, face, and mucous membranes [12]. Histopathologic features include a non-specific psoriasiform pattern [5, 14, 17], acanthosis, papillomatosis, and hyper- and parakeratosis, with necrotic keratinocytes in the superficial epidermis. NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. However, these entities can be distinguished based on clinical and laboratory evaluation [8].
Although a number of mechanisms have been proposed for NAE, there is insufficient evidence to support a precise pathogenesis. The most consistent finding associated with NAE is HCV infection. In fact, there are only four reported cases of NAE without associated HCV infection [3, 4, 8]. Furthermore, two of three studies have observed a correlation between the severity of HCV infection (based on liver enzymes) and the severity of NAE [1, 13, 14]. Additional support comes from cases in which treatment of HCV with ribavarin and INF-α has lead to resolution of NAE [1, 14, 16]. The mechanism by which HCV infection causes NAE is not clear. Attempts to demonstrate HCV viral particles in the involved skin with electron microscopy (for viral particles) or with real time polymerase chain reaction (for HCV RNA) have been unsuccessful [12]. NAE may arise secondary to HCV viral antigen-induced humoral and/or cell-mediated autoimmune responses to viral and/or endogenous cutaneous antigens. Yet another possibility is the development of metabolic abnormalities secondary to hepatocellular dysfunction from HCV infection, which leads to cutaneous manifestations [20, 21].
The next most consistent finding associated with NAE is zinc deficiency, which may result from HCV infection. There are a number of studies that demonstrate decreased zinc levels in patients with NAE [11, 13]. When patients with laboratory evidence of zinc deficiency are treated with zinc (at doses ranging from 60 mg to 440 mg per day), clinical improvement has been noted that ranges from mild to complete resolution [1, 7, 9, 11, 12, 13, 18]. The most consistent improvement is noted at the dose of 440 mg per day. Even in patients with normal serum zinc levels, zinc supplementation has lead to clinical improvement of NAE. It is thought that zinc deficiency may occur in the skin prior to the development of clinical zinc deficiency as assessed by serum zinc levels [22].
Other metabolic conditions that are less clearly associated with NAE are hypoalbuminemia, which is possibly due to the role of albumin as a carrier for essential nutrients that include zinc; hypoaminoacidemia, which is secondary to depletion of epidermal protein and which may increase susceptibility of keratinocytes to necrolysis; and elevated glucagon levels, which are thought to cause elevated levels of pro-inflammatory arachidonic acid and its metabolites [1, 13, 16, 18, 23, 24]. Some authors argue that NAE is a variant of necrolytic migratory erythema (NME) based on the similarity of the clinical and histopathologic features and the proposed pathologic mechanisms, such as hypoalbuminemia and zinc deficiency [13]. The main features that differentiate NAE from NME are the strong association of NAE with HCV infection and the typical localization of NAE to the dorsal aspects of the feet.
Treatment for NAE is not well defined. Because the majority of patients with NAE present without a prior diagnosis of HCV infection, it is imperative to determine HCV infection status in any patient suspected to have NAE. If an infection is identified, the HCV disease severity should be assessed and a treatment plan devised with a hepatologist. An evaluation should be carried out to identify and treat the underlying metabolic deficiency. Zinc therapy (440 mg per day) should be attempted, even in patients with normal serum zinc levels because the probability of benefit outweighs the minimal risk of therapy. There is a single case report that shows improvement with the use of tacrolimus ointment, which may be attempted [6].
References
1. el Darouti M, Abu el Ela M. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252
2. Geria AN, et al. Necrolytic acral erythema: a review of the literature. Cutis 2009; 83:309
3. Nikam BP. Necrolytic acral erythema seronegative for hepatitis C virus - two cases from India treated with oral zinc. Int J Dermatol 2009; 48:1096
4. Wu YH, et al. Necrolytic acral erythema without hepatitis C infection. J Cutan Pathol 2009; 36:355
5. Bentley D, et al. Lack of classic histology should not prevent diagnosis of necrolytic acral erythema. J Am Acad Dermatol 2009; 60:504
6. Manzur A, Siddiqui AH. Necrolytic acral erythema: successful treatment with topical tacrolimus ointment. Int J Dermatol 2008; 47:1073
7. de Carvalho Fantini B, et al. Necrolytic acral erythema successfully treated with oral zinc. Int J Dermatol 2008; 47:872
8. Liu A, et al. Necrolytic acral erythema: a case not associated with hepatitis C infection. Dermatol Online J 2008; 14:10
9. Najarian DJ, et al. Hypozincemia and hyperzincuria associated with necrolytic acral erythema. Int J Dermatol 2008; 47:709
10. Fielder LM, et al. Necrolytic acral erythema: case report and review of the literature. Cutis 2008; 81:355
11. Najarian DJ, et al. Zinc deficiency associated with necrolytic acral erythema. J Am Acad Dermatol 2006; 55:S108
12. El-Ghandour TM, et al. Necrolytic acral erythema in Egyptian patients with hepatitis C virus infection. J Gastroenterol Hepatol 2006; 21:1200
13. Nofal, AA, et al. Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity? Int J Dermatol 2005; 44:916
14. Abdallah MA, et al. Necrolytic acral erythema: a cutaneous sign of hepatitis C virus infection. J Am Acad Dermatol 2005; 53:247
15. Abdallah MA, et al. Necrolytic acral erythema: a patient from the United States successfully treated with oral zinc. Arch Dermatol 2005; 141:85
16. Hivnor CM, et al. Necrolytic acral erythema: response to combination therapy with interferon and ribavirin. J Am Acad Dermatol 2004; 50:S12
17. Abdallah MA, et al. Histological study of necrolytic acral erythema. J Ark Med Soc 2004; 100:354
18. Khanna VJ, et al. Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc. Arch Dermatol 2000; 136:755
19. Frank C, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 2000; 355:887
20. Mason AL, et al. Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 1999; 29:328
21. Hadziyannis SJ. Skin diseases associated with hepatitis C virus infection. J Eur Acad Dermatol Venereol 1998; 10:12
22. Delaporte E, et al. Necrolytic migratory erythema-like eruption in zinc deficiency associated with alcoholic liver disease. Br J Dermatol 1997; 137:1027
23. Jenkins DK, et al. Effects of albumin on fatty acid, protein, eicosanoid levels in rat mesenteric arterial bed perfusions. Can J Physiol Pharmacol. 1998; 66:679
24. Marinkovich MP, et al. Necrolytic migratory erythema without glucagonoma in patients with liver disease. J Am Acad Dermatol 1995; 32:604
Source
Infectious Curiosity
The Hepatitis C virus NS3 serine protease (in gray)
James Griffith, Vertex Pharmaceuticals
The Scientist
Volume 24 Issue 12 Page 24
Date: 2010-12-01
By Jessica Wapner
The course of virologist Charlie Rice's career changed with one phone call in 1989. Then at Washington University in St. Louis, Rice was the country's leading yellow fever expert. The voice on the other end of the line belonged to Stephen Feinstone, an FDA scientist asking about a vaccine for the disease that had just won agency approval. Yellow fever virus is a flavivirus. Feinstone wanted to know if Rice could help develop a vaccine to protect against another flavivirus: hepatitis C. “I can get interested in pretty much anything, I guess,” says Rice.
Today, more than 20 years after Rice took that call, hepatitis C virus (HCV) infects about 170 million people worldwide, but those statistics may soon take a downward turn. Two protease inhibitors that recently completed late-stage clinical trials—telaprevir and boceprevir—are curing significant numbers of patients who may otherwise have suffered a lifetime of liver problems. Published studies reported profound responses to treatment with either of these drugs when used in combination with pegylated interferon (PegIFN) and ribavirin—the current standard, but often ineffective, therapy (J.G. McHutchison et al., NEJM, 360:1827-38, 2009 and P.Y. Kwo et al., Lancet, 376:705-16, 2010).
After that pivotal call from Feinstone, Rice began studying the biology of hepatitis C, a task that attracted little interest in his laboratory at the time. Like a lone archaeologist mapping a forgotten city, Rice charted the structure and function of the virus's various components. His lab group, then at Washington University in St. Louis, found that the HCV polyprotein produced at least ten polypeptides upon cleavage. Rice also identified structural and nonstructural proteins at the polyprotein's N-terminus, several of which would eventually become drug-target candidates. Researchers had already noted the prominent role of serine proteases in flavivirus replication, so Rice and others identified the serine protease in HCV and began to characterize its functional requirements. They found that optimal protease activity depended upon binding to a small viral protein located immediately downstream in viral polypeptide (A. Grakoui et al., J Virol, 67:1385-95, 1993).
Rice was invited in 2000 to lead the newly established Center for the Study of Hepatitis C at Rockefeller University in New York City where he continued to elucidate the molecular biology of the viral serine protease. Because the HCV protease cleaves the polyprotein responsible for viral RNA synthesis at multiple sites, Rice reasoned that the virus probably couldn’t survive if the enzyme's function was blocked. Still, making the leap from the benchtop to an effective therapy required first knowing the exact structure of the protease molecule.
Enter Vertex Pharmaceuticals. After the mid 1990s, when protease inhibitors revolutionized HIV treatment, the company was eager to investigate employing a similar strategy to thwart HCV. Vertex had been keeping tabs on Rice’s HCV work and invited him to collaborate on determining the crystal structure of the protease to aid in drug development.
Rice and Vertex quickly achieved several milestones: development of a biochemical assay, determination of the protease cleavage site specificity, and identification of the residues in the downstream protease cofactor required for optimal activity. Using X-ray crystallography, they determined the crystal structure of the serine protease/cofactor complex. For cell-based studies, Rice built on a landmark study from Ralf Bartenschlager's lab, then at the University of Mainz, Germany, to create highly efficient HCV “replicon” cell culture systems to study the effect of drug candidates on protease activity. “As a result of the development of HCV replicons, scientists now had the ability to screen vast numbers of molecules to test their ability to inhibit HCV replication,” says Ira Jacobson of Weill Cornell Medical College, in New York City.
But knowing the protease’s structure presented a thorny problem—it turned out that the enzyme contained a flat active site. Designing a structure-based drug was going to be like rock-climbing a smooth mountain face. Prepared for this obstacle by some preliminary images, Vertex and Rice were confident that some nook or cranny could be found.
Scientists at Vertex spent months combing the crystal structure for any shred of texture and finally managed to find a few small footholds within the protease’s active site. Vertex’s protease inhibitor, VX-950 (now known as telaprevir), has emerged as a leading agent for the treatment of HCV patients with the genotype-1 strain of the disease. A second compound, boceprevir, developed by Schering-Plough, proved equally effective in those patients. Doctors and HCV patients alike are anxiously awaiting FDA approval of these drugs, expected in 2011.
Still, more work is needed. Although the genotype-1 variant is the most common HCV strain in the United States, other genotypes prevail across Europe, Asia, and Africa. In addition, clinicians are hoping to phase out the use of PegIFN and ribavirin, both of which have toxic side effects. As second-generation HCV protease inhibitors are being developed, and research on the optimal combination regimen continues, Rice’s discoveries remain integral to the future of HCV research and treatment. “There can always be surprises when you’re dealing with a virus in 100 to 200 million people and generating [new] variants every day,” says Rice. “The game is not over at all.”
Source
Sticking Fast To Foil Hepatitis C
Avila Therapeutics
Hanging Tough A covalent inhibitor (blue) binds irreversibly to a cysteine in the substrate-binding site of hepatitis C protease (green). The active site serine is shown in red.
December 1, 2010
Biochemistry: Aiming beyond the active site of a virus's key protease yields selective blockers
Carmen Drahl
By targeting a noncatalytic cysteine, researchers have designed selective irreversible blockers of a protease enzyme essential for hepatitis C virus replication (Nat. Chem. Biol., DOI: 10.1038/nchembio.492).
The work is the first demonstration that steering clear of the active site is a viable design strategy for drugs that react to form a covalent bond to proteases, a broad class of proteins that includes many drug targets. This strategy has already proven useful for blocking other proteins such as kinases.
A team from the biotechnology company Avila Therapeutics developed the new protease blockers, which covalently bind to a cysteine in hepatitis C protease's substrate-binding site. In contrast, most other hepatitis C protease inhibitors in development reversibly bind to a catalytic amino acid common to proteases in human hosts as well as in viruses. Avila's published inhibitor structures are prototypes, but the company hopes to begin human clinical trials with optimized compounds in 2011. The team says its comprehensive structural analysis of hundreds of proteases suggests this strategy can be applied broadly.
However, it's not clear how applicable the team's strategy will be to all proteases, says Matthew S. Bogyo of Stanford University, who develops chemical tools to study the roles of proteases in disease. Nevertheless, "covalent inhibitors benefit from a long duration of action, and when used for clearing pathogens such as hepatitis C virus, they may make more sense than classical reversible inhibitors," Bogyo says. Covalent inhibitors can also make several aspects of drug development more straightforward because it's easier to monitor their target selectivity and distribution throughout the body compared with reversible inhibitors, he adds.
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2010 American Chemical Society
Source
Also See: First-ever covalent irreversible inhibition of a protease central to hepatitis C infection
On the Eve of World Aids Day, Yee Recommits to Sterile Syringe Boll
Office of Senator Leland Yee
SACRAMENTO – On the eve of World AIDS Day, Senator Leland Yee (D-San Francisco) is hoping Governor-elect Jerry Brown (D-Oakland) will heed the advice of doctors, pharmacists, and AIDS prevention advocates, by signing legislation to allow pharmacies to sell sterile syringes to an adult without a prescription.
Governor Arnold Schwarzenegger (R-Los Angeles) recently vetoed Yee's Senate Bill 1029, which would have brought California in line with every other state in the nation (accept two) to no longer prohibit pharmacists from selling a syringe without a prescription.
Today, Senator Yee announced his intention to reintroduce the bill during the upcoming legislative session that begins next week.
Most states amended their laws in light of overwhelming evidence that criminalizing access to sterile syringes led drug users to share used ones, and that sharing syringes spread HIV, hepatitis B, hepatitis C and other blood-borne diseases that can live in a used syringe.
Under an existing pilot program, pharmacies in Los Angeles County, San Francisco, and some other parts of the state have been allowed to sell syringes. While he was mayor of Oakland, Brown's home county of Alameda authorized sterile syringe sales.
Yee's legislation would remove the existing sunset of the pilot program (2018) and would allow all pharmacists throughout the state with the discretion to sell sterile syringes without a prescription.
"AIDS and hepatitis do not recognize county borders and thus our current policy is not nearly as effective as it should be," said Yee. "This legislation will reduce health care costs to taxpayers and save lives. I am hopeful that under Governor Brown's leadership, we will get this bill signed into law."
The approach in Yee's bill has been evaluated extensively throughout the world and has been found to significantly reduce rates of HIV and hepatitis without contributing to any increase in drug use, drug injection, crime or unsafe discard of syringes. In fact, there is not one credible study that refutes these findings.
Alex Kral, an epidemiologist who has supervised several studies of HIV prevention, said, "In light of over 200 studies worldwide that establish improved syringe access means less disease with no downside, to continue a policy of making syringe sales illegal would amount to health policy malpractice."
The 200 studies Kral referred to were reviewed by the World Health Organization (WHO) in 2008. WHO concluded that the overwhelming scientific consensus showed improved syringe access reduced rates of HIV and hepatitis without contributing to drug use, crime or unsafe discard of syringes.
Among the numerous studies cited was one published in the American Journal of Public Health from 2001 that compared US cities that allowed pharmacists to sell syringes to adults without a prescription and those that did not. The study found that the rate of HIV among drug injectors was twice as high in cities that forbid sale without a prescription than those cities that allowed pharmacists greater flexibility to provide syringes.
"Based on a robust body of research, it is clear that Senator Yee's bill will save thousands of lives and hundreds of millions of taxpayer dollars by preventing HIV and hepatitis," said Laura Thomas, MPH, Dep. State Director, Drug Policy Alliance. "We thank Senator Yee for his leadership in promoting effective and affordable HIV and hepatitis prevention efforts."
Sharing of used syringes is the most common cause of new hepatitis C infections in California and the second most common cause of HIV infections. The state Department of Public Health estimates that approximately 3,000 California residents contract hepatitis C through syringe sharing every year and another 750 cases of HIV are caused by syringe sharing.
These diseases are costly and potentially deadly. Hospitalizations for hepatitis B and hepatitis C cost the state $2 billion in 2007, according to a report by the California Research Bureau. The lifetime cost of treating hepatitis C is approximately $100,000, unless a liver transplant is required, and then the cost exceeds $300,000 per surgery. The lifetime cost of treating HIV/AIDS is now estimated to exceed $600,000 per patient.
"Many studies prove that clean syringes can dramatically lower HIV transmission rates," said Courtney Mulhern-Pearson, Director of State & Local Affairs, San Francisco AIDS Foundation. "Sterile syringes not only protect injection drug users, they also protect their sexual partners. Providing broader access to clean syringes is the right thing to do for the health of entire communities across California."
Source
SACRAMENTO – On the eve of World AIDS Day, Senator Leland Yee (D-San Francisco) is hoping Governor-elect Jerry Brown (D-Oakland) will heed the advice of doctors, pharmacists, and AIDS prevention advocates, by signing legislation to allow pharmacies to sell sterile syringes to an adult without a prescription.
Governor Arnold Schwarzenegger (R-Los Angeles) recently vetoed Yee's Senate Bill 1029, which would have brought California in line with every other state in the nation (accept two) to no longer prohibit pharmacists from selling a syringe without a prescription.
Today, Senator Yee announced his intention to reintroduce the bill during the upcoming legislative session that begins next week.
Most states amended their laws in light of overwhelming evidence that criminalizing access to sterile syringes led drug users to share used ones, and that sharing syringes spread HIV, hepatitis B, hepatitis C and other blood-borne diseases that can live in a used syringe.
Under an existing pilot program, pharmacies in Los Angeles County, San Francisco, and some other parts of the state have been allowed to sell syringes. While he was mayor of Oakland, Brown's home county of Alameda authorized sterile syringe sales.
Yee's legislation would remove the existing sunset of the pilot program (2018) and would allow all pharmacists throughout the state with the discretion to sell sterile syringes without a prescription.
"AIDS and hepatitis do not recognize county borders and thus our current policy is not nearly as effective as it should be," said Yee. "This legislation will reduce health care costs to taxpayers and save lives. I am hopeful that under Governor Brown's leadership, we will get this bill signed into law."
The approach in Yee's bill has been evaluated extensively throughout the world and has been found to significantly reduce rates of HIV and hepatitis without contributing to any increase in drug use, drug injection, crime or unsafe discard of syringes. In fact, there is not one credible study that refutes these findings.
Alex Kral, an epidemiologist who has supervised several studies of HIV prevention, said, "In light of over 200 studies worldwide that establish improved syringe access means less disease with no downside, to continue a policy of making syringe sales illegal would amount to health policy malpractice."
The 200 studies Kral referred to were reviewed by the World Health Organization (WHO) in 2008. WHO concluded that the overwhelming scientific consensus showed improved syringe access reduced rates of HIV and hepatitis without contributing to drug use, crime or unsafe discard of syringes.
Among the numerous studies cited was one published in the American Journal of Public Health from 2001 that compared US cities that allowed pharmacists to sell syringes to adults without a prescription and those that did not. The study found that the rate of HIV among drug injectors was twice as high in cities that forbid sale without a prescription than those cities that allowed pharmacists greater flexibility to provide syringes.
"Based on a robust body of research, it is clear that Senator Yee's bill will save thousands of lives and hundreds of millions of taxpayer dollars by preventing HIV and hepatitis," said Laura Thomas, MPH, Dep. State Director, Drug Policy Alliance. "We thank Senator Yee for his leadership in promoting effective and affordable HIV and hepatitis prevention efforts."
Sharing of used syringes is the most common cause of new hepatitis C infections in California and the second most common cause of HIV infections. The state Department of Public Health estimates that approximately 3,000 California residents contract hepatitis C through syringe sharing every year and another 750 cases of HIV are caused by syringe sharing.
These diseases are costly and potentially deadly. Hospitalizations for hepatitis B and hepatitis C cost the state $2 billion in 2007, according to a report by the California Research Bureau. The lifetime cost of treating hepatitis C is approximately $100,000, unless a liver transplant is required, and then the cost exceeds $300,000 per surgery. The lifetime cost of treating HIV/AIDS is now estimated to exceed $600,000 per patient.
"Many studies prove that clean syringes can dramatically lower HIV transmission rates," said Courtney Mulhern-Pearson, Director of State & Local Affairs, San Francisco AIDS Foundation. "Sterile syringes not only protect injection drug users, they also protect their sexual partners. Providing broader access to clean syringes is the right thing to do for the health of entire communities across California."
Source
AASLD: Hepatitis C Vaccine Elicits Immune Response in Some Patients
By: DIANA MAHONEY, Internal Medicine News Digital Network
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
Source
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
Source
November 30, 2010
The World's Illuminated in Red for World AIDS Day
By Shyla Batliwalla
Tuesday, November 30, 2010 6:05 PM ET
Eighty monuments around the world will turn red in support of the (RED) campaign's 2015 goal to have zero children born infected with HIV.
There are currently over 33 million people worldwide living with AIDS. In 2009, nearly half a million babies were born HIV positive; 90 percent of those babies were in Africa. While these statistics might seem grim, there is hope. With proper treatment, spreading HIV to an unborn baby is 99 percent preventable.
Wednesday, Nov. 1 is World AIDS Day. Governments around the world are gearing up to show their support and commitment to ending the AIDS pandemic. In honor of the ongoing fight, over one dozen countries will light up 80 of the most famous landmarks on the planet to promote awareness.
This global movement is sponsored by (RED), an organization that brings together key international corporations to raise funds for HIV/AIDS prevention programs in Africa. Brands like Nike, Starbucks, Gap, American Express and Armani create and sell products exclusively for the (RED) campaign. Fifty percent of the proceeds generated from sales are donated directly to (RED).
Since its inception in 2006, (RED) has generated over $150 million towards the fight against AIDS. The World AIDS day campaign underlines their achievable goal to end mother-to-child transmission of HIV by 2015. When this goal is realized, the first AIDS free generation in 30 years will be created.
As evening sets in Sydney, Australia, the iconic Opera House will be illuminated in red with U2's Bono kicking off the campaign. Time zone by time zone, similarly significant attractions will turn red for just one night. From Table Mountain in South Africa and the London Eye in London to the Empire State Building in New York and LAX in LA, on Wednesday the world will see red as a symbol of hope that an end to the fight against AIDS is near.
(RED) CEO Susan Ellis said, "This is a time of great hope and promise in the battle against AIDS, because we are on the verge of ensuring that virtually no child will come into the world carrying the burden of HIV. Our World AIDS Day awareness campaign, 'The AIDS Free Generation is Due in 2015' is a reminder to everyone that we must work together to overcome the financial challenges at this critical juncture and to keep the world focused on this issue and this achievable goal."
Show your solidarity on Global AIDS day by using Twitter, Facebook, FourSquare and MeetUp to send images and words of support. (RED) will be collecting the data on a map to show how the world is united in the fight against AIDS. With enough support, (RED)'s goal to have zero children born with HIV in 2015 will become a reality.
Source
Study finds anti-microbials a common cause of drug-induced liver injury and failure
Public release date: 30-Nov-2010
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Disproportionate number of women and minorities affected
New research shows that anti-microbial medications are a common cause of drug-induced liver injury (DILI) leading to acute liver failure (ALF), with women and minorities disproportionately affected. While ALF evolves slowly, once it does occur a spontaneous recovery is unlikely; however liver transplantation offers an excellent survival rate. Full findings of this ten-year prospective study are published in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.
Patients with liver failure resulting from DILI may experience deep jaundice, fluid retention, advanced coagulopathy and coma. More than 1100 drugs, herbal remedies, natural products, vitamins, minerals, dietary supplements, and recreational and illicit compounds are known to cause liver injury, which reportedly affect 1 in 100,000 to 1 in 10,000 patients. Prior research shows DILI is a frequent cause of hepatitis, and accounts for 5%-10% of hospitalizations for jaundice and 12% of all cases of ALF (excluding acetaminophen).
In the current study, researchers investigated liver injury and failure caused by drugs other than acetaminophen. Detailed case reports were collected from 1,198 subjects with ALF enrolled at 23 sites participating in the National Institutes of Health-funded Acute Liver Failure Study Group, led by Principal Investigator, William M. Lee, M.D., from the University of Texas Southwestern Medical Center in Dallas, TX. Researchers identified 133 patients with DILI with 71% of those cases in women.
"Our findings confirm prior medical evidence that found a high female predominance in DILI ALF, suggesting that women may be more susceptible to liver injury or use more prescription drugs than men," said Dr. Adrian Reuben, Professor of Medicine at the Medical University of South Carolina and lead study author.
Furthermore, the research team documented a disproportionately high number of minorities with DILI ALF, including African-American (16%), Hispanic (15%) and other minority groups (12%). "We observed inexplicably high numbers of minority patients with DILI ALF. This racial disparity is atypical for acetaminophen-induced ALF in the U.S. and further studies should explore this discrepancy," commented Dr. Reuben.
Researchers identified 61 different agents that, alone or in combination, could cause liver injury and failure in the study population. Anti-microbial agents were found to be the most common cause of DILI ALF cases and included anti-tuberculosis drugs (25), sulphur-containing drugs (12), nitrofurantoin (12), other antibiotics (7), antifungal agents (6), and anti-retroviral drugs (4). Patients who develop ALF after taking these drugs typically do not experience a spontaneous recovery—the transplant-free survival rate in this study was 27%.
There were 56 eligible subjects who underwent liver transplantation of whom all but four survived, giving an overall survival for the entire cohort 66.2%. The authors highlight that the 23.3% of transplantation waitlist deaths attest to the urgent need for donor organs in this setting. "Liver transplantation offers excellent survival for ALF patients, however further investigation should include more detail on drug use duration, and the impact of alcohol use and diabetes, to provide additional understanding of idiosyncratic drug-induced liver injury and failure," Dr. Reuben concluded.
###
Article: "Drug-Induced Acute Liver Failure: Results of a United States Multicenter, Prospective Study." Adrian Reuben, David G. Koch, William M. Lee and the Acute Liver Failure Study Group. Hepatology; Published Online: October 14, 2010 (DOI: 10.1002/hep.23937); Print Issue Date: December 2010. http://doi.wiley.com/10.1002/hep.23937.
This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350.
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Disproportionate number of women and minorities affected
New research shows that anti-microbial medications are a common cause of drug-induced liver injury (DILI) leading to acute liver failure (ALF), with women and minorities disproportionately affected. While ALF evolves slowly, once it does occur a spontaneous recovery is unlikely; however liver transplantation offers an excellent survival rate. Full findings of this ten-year prospective study are published in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.
Patients with liver failure resulting from DILI may experience deep jaundice, fluid retention, advanced coagulopathy and coma. More than 1100 drugs, herbal remedies, natural products, vitamins, minerals, dietary supplements, and recreational and illicit compounds are known to cause liver injury, which reportedly affect 1 in 100,000 to 1 in 10,000 patients. Prior research shows DILI is a frequent cause of hepatitis, and accounts for 5%-10% of hospitalizations for jaundice and 12% of all cases of ALF (excluding acetaminophen).
In the current study, researchers investigated liver injury and failure caused by drugs other than acetaminophen. Detailed case reports were collected from 1,198 subjects with ALF enrolled at 23 sites participating in the National Institutes of Health-funded Acute Liver Failure Study Group, led by Principal Investigator, William M. Lee, M.D., from the University of Texas Southwestern Medical Center in Dallas, TX. Researchers identified 133 patients with DILI with 71% of those cases in women.
"Our findings confirm prior medical evidence that found a high female predominance in DILI ALF, suggesting that women may be more susceptible to liver injury or use more prescription drugs than men," said Dr. Adrian Reuben, Professor of Medicine at the Medical University of South Carolina and lead study author.
Furthermore, the research team documented a disproportionately high number of minorities with DILI ALF, including African-American (16%), Hispanic (15%) and other minority groups (12%). "We observed inexplicably high numbers of minority patients with DILI ALF. This racial disparity is atypical for acetaminophen-induced ALF in the U.S. and further studies should explore this discrepancy," commented Dr. Reuben.
Researchers identified 61 different agents that, alone or in combination, could cause liver injury and failure in the study population. Anti-microbial agents were found to be the most common cause of DILI ALF cases and included anti-tuberculosis drugs (25), sulphur-containing drugs (12), nitrofurantoin (12), other antibiotics (7), antifungal agents (6), and anti-retroviral drugs (4). Patients who develop ALF after taking these drugs typically do not experience a spontaneous recovery—the transplant-free survival rate in this study was 27%.
There were 56 eligible subjects who underwent liver transplantation of whom all but four survived, giving an overall survival for the entire cohort 66.2%. The authors highlight that the 23.3% of transplantation waitlist deaths attest to the urgent need for donor organs in this setting. "Liver transplantation offers excellent survival for ALF patients, however further investigation should include more detail on drug use duration, and the impact of alcohol use and diabetes, to provide additional understanding of idiosyncratic drug-induced liver injury and failure," Dr. Reuben concluded.
###
Article: "Drug-Induced Acute Liver Failure: Results of a United States Multicenter, Prospective Study." Adrian Reuben, David G. Koch, William M. Lee and the Acute Liver Failure Study Group. Hepatology; Published Online: October 14, 2010 (DOI: 10.1002/hep.23937); Print Issue Date: December 2010. http://doi.wiley.com/10.1002/hep.23937.
This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350.
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
Mymetics HIV Vaccine Shows Strong Preliminary Phase I Data
PRESS RELEASE
Nov. 30, 2010, 8:10 a.m. EST
HIV-1 Vaccine Designed to Block Early Transmission and Infection Events, Preventing Virus From Settling and Spreading Within the Body; In Phase I Trial, Vaccine Generated Both Serum Antibodies and Mucosal Antibodies in the Genital and Intestinal Tracts
EPALINGES, SWITZERLAND, Nov 30, 2010 (MARKETWIRE via COMTEX) -- Mymetics Corporation /quotes/comstock/11k!mymx (MYMX 0.13, +0.01, +8.33%) , a pioneer in the development of vaccines preventing mucosal transmission of human infectious diseases, announced today strong preliminary results of a Phase I trial on its promising HIV vaccine, MYMV101. Unlike most current vaccines, seeking to eliminate pathogens once they have already entered the bloodstream, Mymetics' vaccines are designed to block early transmission and infection events, preventing virus from settling and spreading within the body. This represents a highly promising but, until now, poorly investigated approach to preventing HIV infection.
The Phase I trial was conducted on 24 healthy women. The vaccine was well tolerated and immunogenic in both low and high dose vaccinated groups. The majority of volunteers developed not only serum antibodies but also mucosal antibodies in the genital and intestinal tracts.
"These new results represent a major achievement for Mymetics," commented Sylvain Fleury, CSO of Mymetics. "Very few HIV vaccine candidates developed over the last 25 years could elicit both blood and mucosal antibodies as a front-line defense mechanism against the entry of HIV-1 across mucosal tissues."
Jacques-Francois Martin, CEO of Mymetics, added, "Our vaccine represents a first line of defense before the virus can settle in the tissue and spread within the body. These preliminary Phase I results in HIV-1/AIDS represent an important validation of our pioneering work and approach. They also confirm a previous preclinical study where the vaccine provided unprecedented 100% protection in primates."
The Phase I trial, started in December 2009, is a placebo-controlled, double-blind, single-site study, conducted by Prof. G. Leroux-Roels at the Center for Vaccinology (CEVAC) at the University of Ghent (Belgium), under the supervision of Kinesis-Pharma, a CRO under contract with Mymetics. During the vaccination, women received high or low dose vaccinations. The first two injections were performed intra-muscularly and the last two via intra-nasal spray. The final clinical report is expected in January 2011, which will then also include the analysis of the neutralizing characteristics of the antibodies.
HIV-1, the virus that causes AIDS, is primarily transmitted through sexual contact, exposing the mucosal tissues of the genital organs as the first entry door for the virus before it reaches the blood. HIV-1 infected about 2.7 million new people in 2008, while an estimated 2 million people died of AIDS in the same year. HIV-1-related illness remains one of the leading causes of death globally and is projected to remain a significant cause of premature mortality in the coming decades.
Mymetics' vaccine strategy The vast majority of pathogens enter their target hosts through mucosal surfaces such as the respiratory, genito-urinary or gastrointestinal tracts. Once they have reached the blood, pathogens can migrate to various organs where they replicate. Most current vaccines seek to eliminate pathogens once they have already entered the bloodstream, by which time control of the pathogen can be significantly more challenging (e.g. HIV-1). Classical vaccines work by inducing mostly blood antibodies (mainly IgG) and are poor at triggering the antibodies that predominate in all mucosal tissues (mainly IgA).
Mymetics has created a vaccine against HIV-1, using its virosome technology and judicious antigen design. The vaccine primarily induces mucosal antibodies, preventing HIV-1 attachment to epithelial cells and providing an efficient first line of defense on mucosal surface such as the genital tract. The vaccine also induces blood antibodies, which will ideally function as a complementary second line of defense. By minimizing homology between the vaccine and native human proteins, Mymetics further aims to avoid auto-immune complications resulting from cross-reactivity.
About CEVAC The Center for Vaccinology (CEVAC) is an academic research unit affiliated with Ghent University and located in the Ghent University Hospital (Ghent, Belgium), and that provides a wide array of services to the biotech industry and vaccine manufacturers. CEVAC conducts Phase I, II and III clinical vaccine trials according to ICH-GCP standards and offers a panel of laboratory services in the field of immunology and vaccinology, such as serological tests, cytokine measurements, B and T lymphocyte detection and function assays. More information can be retrieved at http://www.cevac.be/.
About Kinesis Kinesis Pharma B.V. (founded 1997) is an independent, privately owned drug development consultancy and contract research organization. Kinesis operates internationally with headquarters in Breda (The Netherlands) and a regional office in Singapore. The organization leverages the expertise and experience of its highly-skilled, multi-disciplinary workforce to accelerate drug development. Kinesis Pharma facilitates fast and high quality development and registration of medicinal products with consultancy services in Chemistry, Manufacturing and Control- (CMC), non-clinical- and clinical development and regulatory support. Kinesis operates in close collaboration with pharmaceutical, nutraceutical and biotech companies and has successfully managed the development and registration of pharmaceutical and biotechnology-derived products in different therapeutic areas, including infectious diseases.
About Mymetics Mymetics Corporation is a Swiss-based biotechnology company registered in the US /quotes/comstock/11k!mymx (MYMX 0.13, +0.01, +8.33%) developing next-generation preventative vaccines for infectious diseases. Mymetics' core technology and expertise are centered on the use of virosomes, lipid-based carriers containing functional fusion viral proteins, in combination with rationally designed antigens. The company's vaccines are designed to induce protection against early transmission and infection, focusing on the mucosal immune response as a first-line defense, which for some pathogens may be essential for the development of an effective vaccine. Mymetics is led by an experienced, international management team and is supported by a strong Scientific Advisory Board composed of renowned experts. The company has established contacts with world leaders in vaccine development.
Mymetics currently has 5 vaccines in its pipeline: HIV-1/AIDS, Influenza, Respiratory Syncytial Virus, Malaria and Herpes Simplex Virus. The company's HIV vaccine is entering a new proof-of-concept preclinical trial following unprecedented results in a first study, and is completing a Phase I clinical trial in human volunteers. A Phase 1b clinical trial for its Malaria vaccine on children in Tanzania has been completed, while RSV and HSV vaccine candidates are in the preclinical phase. The Influenza vaccine has been out-licensed to Solvay Pharmaceuticals (now Abbott). For further information, please visit http://www.mymetics.com/.
Forward-looking statements
The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for forward-looking statements, which are identified by the words "believe," "expect," "anticipate," "intend," "plan" and similar expressions. The statements contained herein which are not based on historical facts are forward-looking statements that involve known and unknown risks and uncertainties that could significantly affect our actual results, performance or achievements in the future and, accordingly, such actual results, performance or achievements may materially differ from those expressed or implied in any forward-looking statements made by or on our behalf. These risks and uncertainties include, but are not limited to, risks associated with our ability to successfully develop and protect our intellectual property, our ability to raise additional capital to fund future operations and compliance with applicable laws and changes in such laws and the administration of such laws. See Mymetics' most recent Form 10-K for a discussion of such risks, uncertainties and other factors. Readers are cautioned not to place undue reliance on these forward- looking statements which speak only as of the date the statements were made.Contact:
Ronald Kempers
CFO and COO
Mymetics Corporation
Tel: +41 21 653 4535
U.S. Media:
Michelle Linn
Linnden Communications
Tel: 508-362-3087
Email: Email Contact
Media:
Christophe Lamps
Senior Partner
Dynamics Group
Mobile: + 41 79 476 26 87
Email: Email Contact
Source
Nov. 30, 2010, 8:10 a.m. EST
HIV-1 Vaccine Designed to Block Early Transmission and Infection Events, Preventing Virus From Settling and Spreading Within the Body; In Phase I Trial, Vaccine Generated Both Serum Antibodies and Mucosal Antibodies in the Genital and Intestinal Tracts
EPALINGES, SWITZERLAND, Nov 30, 2010 (MARKETWIRE via COMTEX) -- Mymetics Corporation /quotes/comstock/11k!mymx (MYMX 0.13, +0.01, +8.33%) , a pioneer in the development of vaccines preventing mucosal transmission of human infectious diseases, announced today strong preliminary results of a Phase I trial on its promising HIV vaccine, MYMV101. Unlike most current vaccines, seeking to eliminate pathogens once they have already entered the bloodstream, Mymetics' vaccines are designed to block early transmission and infection events, preventing virus from settling and spreading within the body. This represents a highly promising but, until now, poorly investigated approach to preventing HIV infection.
The Phase I trial was conducted on 24 healthy women. The vaccine was well tolerated and immunogenic in both low and high dose vaccinated groups. The majority of volunteers developed not only serum antibodies but also mucosal antibodies in the genital and intestinal tracts.
"These new results represent a major achievement for Mymetics," commented Sylvain Fleury, CSO of Mymetics. "Very few HIV vaccine candidates developed over the last 25 years could elicit both blood and mucosal antibodies as a front-line defense mechanism against the entry of HIV-1 across mucosal tissues."
Jacques-Francois Martin, CEO of Mymetics, added, "Our vaccine represents a first line of defense before the virus can settle in the tissue and spread within the body. These preliminary Phase I results in HIV-1/AIDS represent an important validation of our pioneering work and approach. They also confirm a previous preclinical study where the vaccine provided unprecedented 100% protection in primates."
The Phase I trial, started in December 2009, is a placebo-controlled, double-blind, single-site study, conducted by Prof. G. Leroux-Roels at the Center for Vaccinology (CEVAC) at the University of Ghent (Belgium), under the supervision of Kinesis-Pharma, a CRO under contract with Mymetics. During the vaccination, women received high or low dose vaccinations. The first two injections were performed intra-muscularly and the last two via intra-nasal spray. The final clinical report is expected in January 2011, which will then also include the analysis of the neutralizing characteristics of the antibodies.
HIV-1, the virus that causes AIDS, is primarily transmitted through sexual contact, exposing the mucosal tissues of the genital organs as the first entry door for the virus before it reaches the blood. HIV-1 infected about 2.7 million new people in 2008, while an estimated 2 million people died of AIDS in the same year. HIV-1-related illness remains one of the leading causes of death globally and is projected to remain a significant cause of premature mortality in the coming decades.
Mymetics' vaccine strategy The vast majority of pathogens enter their target hosts through mucosal surfaces such as the respiratory, genito-urinary or gastrointestinal tracts. Once they have reached the blood, pathogens can migrate to various organs where they replicate. Most current vaccines seek to eliminate pathogens once they have already entered the bloodstream, by which time control of the pathogen can be significantly more challenging (e.g. HIV-1). Classical vaccines work by inducing mostly blood antibodies (mainly IgG) and are poor at triggering the antibodies that predominate in all mucosal tissues (mainly IgA).
Mymetics has created a vaccine against HIV-1, using its virosome technology and judicious antigen design. The vaccine primarily induces mucosal antibodies, preventing HIV-1 attachment to epithelial cells and providing an efficient first line of defense on mucosal surface such as the genital tract. The vaccine also induces blood antibodies, which will ideally function as a complementary second line of defense. By minimizing homology between the vaccine and native human proteins, Mymetics further aims to avoid auto-immune complications resulting from cross-reactivity.
About CEVAC The Center for Vaccinology (CEVAC) is an academic research unit affiliated with Ghent University and located in the Ghent University Hospital (Ghent, Belgium), and that provides a wide array of services to the biotech industry and vaccine manufacturers. CEVAC conducts Phase I, II and III clinical vaccine trials according to ICH-GCP standards and offers a panel of laboratory services in the field of immunology and vaccinology, such as serological tests, cytokine measurements, B and T lymphocyte detection and function assays. More information can be retrieved at http://www.cevac.be/.
About Kinesis Kinesis Pharma B.V. (founded 1997) is an independent, privately owned drug development consultancy and contract research organization. Kinesis operates internationally with headquarters in Breda (The Netherlands) and a regional office in Singapore. The organization leverages the expertise and experience of its highly-skilled, multi-disciplinary workforce to accelerate drug development. Kinesis Pharma facilitates fast and high quality development and registration of medicinal products with consultancy services in Chemistry, Manufacturing and Control- (CMC), non-clinical- and clinical development and regulatory support. Kinesis operates in close collaboration with pharmaceutical, nutraceutical and biotech companies and has successfully managed the development and registration of pharmaceutical and biotechnology-derived products in different therapeutic areas, including infectious diseases.
About Mymetics Mymetics Corporation is a Swiss-based biotechnology company registered in the US /quotes/comstock/11k!mymx (MYMX 0.13, +0.01, +8.33%) developing next-generation preventative vaccines for infectious diseases. Mymetics' core technology and expertise are centered on the use of virosomes, lipid-based carriers containing functional fusion viral proteins, in combination with rationally designed antigens. The company's vaccines are designed to induce protection against early transmission and infection, focusing on the mucosal immune response as a first-line defense, which for some pathogens may be essential for the development of an effective vaccine. Mymetics is led by an experienced, international management team and is supported by a strong Scientific Advisory Board composed of renowned experts. The company has established contacts with world leaders in vaccine development.
Mymetics currently has 5 vaccines in its pipeline: HIV-1/AIDS, Influenza, Respiratory Syncytial Virus, Malaria and Herpes Simplex Virus. The company's HIV vaccine is entering a new proof-of-concept preclinical trial following unprecedented results in a first study, and is completing a Phase I clinical trial in human volunteers. A Phase 1b clinical trial for its Malaria vaccine on children in Tanzania has been completed, while RSV and HSV vaccine candidates are in the preclinical phase. The Influenza vaccine has been out-licensed to Solvay Pharmaceuticals (now Abbott). For further information, please visit http://www.mymetics.com/.
Forward-looking statements
The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for forward-looking statements, which are identified by the words "believe," "expect," "anticipate," "intend," "plan" and similar expressions. The statements contained herein which are not based on historical facts are forward-looking statements that involve known and unknown risks and uncertainties that could significantly affect our actual results, performance or achievements in the future and, accordingly, such actual results, performance or achievements may materially differ from those expressed or implied in any forward-looking statements made by or on our behalf. These risks and uncertainties include, but are not limited to, risks associated with our ability to successfully develop and protect our intellectual property, our ability to raise additional capital to fund future operations and compliance with applicable laws and changes in such laws and the administration of such laws. See Mymetics' most recent Form 10-K for a discussion of such risks, uncertainties and other factors. Readers are cautioned not to place undue reliance on these forward- looking statements which speak only as of the date the statements were made.Contact:
Ronald Kempers
CFO and COO
Mymetics Corporation
Tel: +41 21 653 4535
U.S. Media:
Michelle Linn
Linnden Communications
Tel: 508-362-3087
Email: Email Contact
Media:
Christophe Lamps
Senior Partner
Dynamics Group
Mobile: + 41 79 476 26 87
Email: Email Contact
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On Eve of World AIDS Day, UNICEF Report Says Virtual Elimination of Pediatric HIV/AIDS Appears Within Reach
WASHINGTON, Nov. 30, 2010 /PRNewswire-USNewswire/ -- As the world prepares to commemorate World AIDS Day on December 1, UNICEF released their report, "Unite for Children, Unite Against AIDS," declaring that the achievable goal of eliminating HIV infections in children is the new global measure of success in the fight against pediatric AIDS.
Children and AIDS: Fifth Stocktaking Report, 2010 offers key insights into the changing landscape of HIV/AIDS prevention, care, and treatment for children, and documents that those on the frontlines of the epidemic have turned a significant corner in scaling-up prevention of mother-to-child transmission (PMTCT) of HIV services worldwide.
"The momentum of the global health community behind the elimination of pediatric HIV and AIDS should be applauded," said Charles Lyons, President and CEO of the Elizabeth Glaser Pediatric AIDS Foundation. "We must build on our success, scale-up what we know works, and encourage new innovations to overcome even the greatest of obstacles."
The UNICEF report highlighted that while overall progress is real and should be recognized, many challenges remain. Although a majority of HIV-positive pregnant women in low- and middle-income countries are receiving antiretroviral (ARV) drugs to prevent transmission of the virus to their infants, the report suggests that all pregnant women living with HIV must have access to the more complex drug regimens called for under the new World Health Organization (WHO) guidelines for PMTCT. Implementing and sustaining these benefits worldwide will require full integration of PMTCT services within national maternal and child health programs.
The report also cites significant gains in PMTCT coverage, but also notes that only one-third of infants born to HIV-positive mothers receive ARVs to prevent transmission, increasing only slightly from 2008. Significant improvements are needed for mothers and mother-baby pairs to ensure that services continue during breastfeeding, all babies are tested early for HIV, and every HIV-infected infant get onto therapy as soon as possible.
Pioneering solutions must also be employed to better engage communities and create demand for these services and ensure that women and babies remain in care. While the goal is to have every woman deliver in a health facility, obstacles such as severe weather or lengthy travel distances often result in women delivering their babies at home. As a way to overcome some of these issues, the Elizabeth Glaser Pediatric AIDS Foundation joined with UNICEF last month to launch the Mother Baby Pack (MBP). Created to tackle logistical challenges in delivering critical medicines to pregnant mothers and their newborn babies, the MBP is given to mothers during their first prenatal visit, and contains the antiretroviral drugs (ARVs) and prophylactic antibiotics needed to prevent HIV transmission from mother to baby.
"There are still more than 1,000 babies newly infected with HIV every day. Virtually every one of those infections is preventable," said Lyons. "Reaching mothers and babies around the world with the services they need to prevent the spread of HIV is not only the right thing to do, it will also help us realize a generation born free of HIV."
About the Foundation:
The Foundation is a global leader in the fight against pediatric HIV and AIDS, and has reached nearly 10 million women with services to prevent transmission of HIV to their babies. It works at 5,000 sites in 17 countries to implement prevention, care, and treatment services; to further advance innovative research; and to execute strategic and targeted global advocacy activities in order to bring dramatic change to the lives of millions of women, children, and families worldwide.
SOURCE Elizabeth Glaser Pediatric AIDS Foundation
RELATED LINKS
http://www.pedaids.org/
Source
Children and AIDS: Fifth Stocktaking Report, 2010 offers key insights into the changing landscape of HIV/AIDS prevention, care, and treatment for children, and documents that those on the frontlines of the epidemic have turned a significant corner in scaling-up prevention of mother-to-child transmission (PMTCT) of HIV services worldwide.
"The momentum of the global health community behind the elimination of pediatric HIV and AIDS should be applauded," said Charles Lyons, President and CEO of the Elizabeth Glaser Pediatric AIDS Foundation. "We must build on our success, scale-up what we know works, and encourage new innovations to overcome even the greatest of obstacles."
The UNICEF report highlighted that while overall progress is real and should be recognized, many challenges remain. Although a majority of HIV-positive pregnant women in low- and middle-income countries are receiving antiretroviral (ARV) drugs to prevent transmission of the virus to their infants, the report suggests that all pregnant women living with HIV must have access to the more complex drug regimens called for under the new World Health Organization (WHO) guidelines for PMTCT. Implementing and sustaining these benefits worldwide will require full integration of PMTCT services within national maternal and child health programs.
The report also cites significant gains in PMTCT coverage, but also notes that only one-third of infants born to HIV-positive mothers receive ARVs to prevent transmission, increasing only slightly from 2008. Significant improvements are needed for mothers and mother-baby pairs to ensure that services continue during breastfeeding, all babies are tested early for HIV, and every HIV-infected infant get onto therapy as soon as possible.
Pioneering solutions must also be employed to better engage communities and create demand for these services and ensure that women and babies remain in care. While the goal is to have every woman deliver in a health facility, obstacles such as severe weather or lengthy travel distances often result in women delivering their babies at home. As a way to overcome some of these issues, the Elizabeth Glaser Pediatric AIDS Foundation joined with UNICEF last month to launch the Mother Baby Pack (MBP). Created to tackle logistical challenges in delivering critical medicines to pregnant mothers and their newborn babies, the MBP is given to mothers during their first prenatal visit, and contains the antiretroviral drugs (ARVs) and prophylactic antibiotics needed to prevent HIV transmission from mother to baby.
"There are still more than 1,000 babies newly infected with HIV every day. Virtually every one of those infections is preventable," said Lyons. "Reaching mothers and babies around the world with the services they need to prevent the spread of HIV is not only the right thing to do, it will also help us realize a generation born free of HIV."
About the Foundation:
The Foundation is a global leader in the fight against pediatric HIV and AIDS, and has reached nearly 10 million women with services to prevent transmission of HIV to their babies. It works at 5,000 sites in 17 countries to implement prevention, care, and treatment services; to further advance innovative research; and to execute strategic and targeted global advocacy activities in order to bring dramatic change to the lives of millions of women, children, and families worldwide.
SOURCE Elizabeth Glaser Pediatric AIDS Foundation
RELATED LINKS
http://www.pedaids.org/
Source
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