Main : Understanding HCV Archives

August 17, 2006

Esophogeal Varices

While not well known, the condition known as a bleeding esophogeal varice poses a very real threat to those suffering from a compromised liver. Learn what makes this condition so dangerous and learn how best to stop the bleeding and restore normal blood circulation.

by Nicole Cutler, L.Ac.

Occurring in approximately one in every 10,000 people, bleeding esophogeal varices are swollen veins in the esophagus or the upper part of the stomach that begin to bleed. They can be a life-threatening complication of portal hypertension, where there is increased blood pressure in the primary blood vessel leading into the liver. Because veins are not designed to handle high internal pressure, the engorgement of veins causes them to be fragile and bleed easily. If a large volume of blood is lost, signs of shock will develop (pallor, a rapid and weak pulse, rapid and shallow respiration and lowered systemic blood pressure).

Common culprit
Alcoholic and viral cirrhosis are the leading causes of portal hypertension in Western countries. As liver disease progresses, the risk of developing cirrhosis follows. Cirrhosis is the permanent scarring and hardening of liver tissue, which subsequently prohibits hepatic circulation. This hampering of blood flow through the liver increases the hepatic pressure that causes portal hypertension and sets the stage for blood vessels to burst. A bleeding esophogeal varice is the most serious complication in patients with cirrhotic liver disease.

To read the complete article, including how to treat and prevent this serious condition click here.

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June 05, 2006

Dangerous Over-the-Counter Meds

If you suffer from liver disease, learn why it's important to read the labels of any over the counter pain medicine or cold remedy before placing them in your shopping cart. Discover how acetaminophen may play a role in accelerating liver failure in hepatitis patients.

LOS ANGELES (May 21, 2006) Acetaminophen as a Co-Factor in Acute Liver Failure Due to Viral Hepatitis Determined by Measurement of Acetaminophen-Protein Adducts [Abstract S1002]

Acetaminophen (APAP) is a common over-the-counter medication present in more than 300 preparations for pain relief and flu-like symptoms. But for people who are suffering from viral hepatitis A or B, use of acetaminophen may play a role in accelerating liver failure, ordinarily a rare complication of viral hepatitis.

Serum samples from 72 patients with proven hepatitis A or B that had progressed to liver failure were tested for APAP adducts, which are the toxic byproducts of acetaminophen liver damage, created when a chemical (in this case, acetaminophen) binds to proteins in the liver that are then released into the blood when cells die. As a positive control group, the team also included 10 documented cases of acute liver failure (ALF) resulting directly from large APAP overdoses.

Results from the examination showed that nine of the 72 patients (12.5 percent) had detectable APAP adducts in their blood, signifying that some of their liver damage was APAP-related. All 10 known APAP-induced ALF cases had positive adducts at much higher levels than those in the viral hepatitis group (average level of 5.58 nmol/mL versus 0.45 nmol/mL, respectively). Two-thirds (67 percent) of the hepatitis patients with APAP adducts died within three weeks of study admission, compared to only 27 percent of hepatitis patients without adducts.

Most of the patients with adducts reported some APAP use in the days prior to the study, but none reported doses exceeding four grams per day. Flu-like symptoms, nausea and vomiting are common in patients with early viral hepatitis and APAP is commonly used in this setting.

"This study suggests that acetaminophen, even when taken at therapeutic dosages, is responsible for a second hit in viral hepatitis and explains why some patients develop acute liver failure and death in this setting," said William M. Lee, M.D., of the UT Southwestern Medical Center in Texas, and senior study author. "Warnings regarding use of acetaminophen should be clearly communicated to patients with acute viral hepatitis, particularly those of moderate severity, to reduce these bad outcomes from a relatively benign disease."

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Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 20-25, 2006 in Los Angeles, California. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

Reprinted with permission of Digestive Disease Week® 2006.

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April 18, 2006

A New Study on HIV/HCV Co-Infection and Race

A new study on HIV and HCV co-infection confirms a significantly greater mortality rate for individuals infected with both viruses than those infected with only one. Researchers also reported that for yet unexplained reasons, white people are twice as likely to die from co-infection than black people.

Whites fare poorly with HIV and hepatitis C

Will Boggs, MD
Reuters
April 18, 2006

NEW YORK (Reuters Health) - Liver disease and death rates are worse with hepatitis C virus (HCV) infection on top of HIV infection than with just HIV or HCV, especially among white patients, according to a new report.

"We need to better understand why the co-infected patients do so poorly and the underlying mechanism for apparent racial disparity in their outcome," Dr. Kyong-Mi Chang, told Reuters Health.
"We also need better drugs that directly target HCV," added Chang, from the University of Pennsylvania and Philadelphia Veterans Affairs Medical Center.

Chang's team examined the impact of dual infection and race in 265 veterans with HCV/HIV co-infection, 251 infected with HCV only, and 227 others with HIV only.

Over a three-year period, mortality was significantly greater among HCV/HIV-co-infected patients than among patients mono-infected with either HCV or HIV, the researchers report in the American Journal of Gastroenterology.

Specifically, after taking into account a variety of factors, mono-infected patients were only about one-third as likely to die as dual-infected patients.

During the study period, twice as many white patients died compared to black patients, the report indicates.

Also, the average age at death in white patients (46 years) was significantly younger than that in black patients (52 years).

Since dual-infected patients fare so poorly, Chang said, the team aims to treat them "as much as possible and monitor them closely for liver dysfunction." He said specialists in liver disease and infectious diseases "as well as pharmacists (also social work and mental health support), is needed to optimize therapy for these complex patients."

SOURCE: American Journal of Gastroenterology, April 2006.

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June 11, 2005

Science Finally Replicates HCV in Lab

This breakthrough will go a long way toward helping develop more effective treatments for HCV (and maybe even a vaccine).

'Test tube' hope for hep C drug

Around 3% of people worldwide are thought to have hepatitis C.

US scientists have been able to create infectious hepatitis C in the lab for the first time, offering renewed hope of drugs to beat the virus.

Hepatitis C is a major cause of chronic and sometimes fatal liver disease, affecting 170 million people worldwide.

The virus, HCV, is carried in and can be passed on via the blood.

Currently, it is treated with a combination of two drugs, but about 40% of patients do not respond to this therapy.

This may help in the development of new drugs for combating HCV
Study author Dr Charles Rice

Like all viruses, hepatitis C cannot replicate by itself. It takes over the machinery of the host cell.

However, much about the life cycle of the virus remains poorly understood because, until now, scientists have been unable to reproduce an infectious form of HCV that they can observe and experiment on in the lab.

"This system lays the foundation for future test tube studies of the virus life cycle and may help in the development of new drugs for combating HCV," said researcher Dr Charles Rice from the Infectious Diseases Unit at Rockefeller University.

Achilles' heel

He told the journal Science how in a separate set of experiments they were able to use the lab-grown virus to confirm that a molecule called CD81, which sits on the surface of human cells, plays a crucial role in the entry of HCV.

They found that CD81 molecules which were not attached to the surface of host cells competed with cell-bound CD81 and blocked the entry of HCV into the cell. Furthermore, cells that did not express CD81 were immune to infection.

Scientists already know that a protein produced by HCV, called E2, binds to CD81. It is believed this interaction is necessary for the virus to bind to host cells.

Chief executive of the Hepatitis C Trust and president of the European Liver Patients Association, Charles Gore, said: "Treatment for hepatitis C has improved dramatically in recent years but there is still considerable room for improvement.

"This is one of the reasons why so few - just one-half to one percent - of those with this unacknowledged virus are getting treated each year.

"Any advances that can contribute to improved therapy, and especially the development of a vaccine, are good news for patients."

Dr Teo, consultant virologist at the Centre for Infections, the Health Protection Agency, said: "The ability to culture HCV is the holy grail of HCV research because this will help with improving testing techniques, allow better understanding about how the virus causes illness and help us to explore better treatments for the disease."

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June 09, 2005

HCV Evasive Strategy Being Decoded

While a bit technical I found this article very interesting and informative.

Public release date: 9-Jun-2005

Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions

Johns Hopkins team finds 'ancestral' hepatitis-C virus at the root of evolution in infections

Scientists discover how virus evades immune system in acute and chronic infections; new vaccines may result.

Researchers at Johns Hopkins have uncovered how a majority of the genetic changes in the hepatic-C virus, the most common cause of liver disease, allow it to evade the body's immune system during infection. Hepatitis C infection can lead to cirrhosis, cancer and even death. In a series of experiments that describe the virus' transition from an acute to chronic infection, the Hopkins team found that one-half of the virus' changes in its genome are in sites under attack by the body's immune system.

As the virus evolves and these changes weaken the body's immune response, a second set of changes at other sites in the genome are reverting back to an "ancestral" set of amino acids.

"We think this piecemeal exchange is helping the virus evade the body's immune system," says study investigator and infectious disease specialist Stuart Ray, M.D., an associate professor at The Johns Hopkins University School of Medicine. "In a newly infected person, the virus may need to adopt new mutations to escape recognition by the immune system's T cells, which fight infection, but it may need to lose the mutations that had protected it in someone else. Despite pressure to change, the virus is always is restoring its shape."

The Hopkins findings, published in a pair of studies in the Journal of Experimental Medicine this week, are believed to be the first description of the precise genetic changes taking place in the virus during the acute phase of infection, when hepatitis C initially escapes the body's defenses and establishes itself in the body. As the infection moves into the chronic stage, the immune response becomes weak and less effective, but until now, no one could explain exactly why.

A second, related experiment produced similar findings when the Hopkins team partnered with researchers in Ireland to perform what is believed to be the first comparison of genetic changes across multiple genes in strains from chronically infected people to the original strain that infected them.

Ray, who served as senior investigator on the first study and led the second, believes the newly identified ancestral component of the viral genome, called a consensus sequence, could serve as the basis for development of a vaccine that is effective against both acute and chronic infections, thereby stemming the epidemic that currently afflicts more than 170 million people worldwide, including 3 million Americans.

"Hepatitis C is extremely difficult to treat if it becomes chronic," says infectious disease specialist Andrea Cox, M.D., Ph.D., an assistant professor at Hopkins who was lead author of the first study. "While approximately 30 percent of patients have a strong enough immune response to rid themselves of the virus during the acute phase, and current treatments are 90 percent effective at treating any remaining acute infections, these treatments are only 50 percent effective against chronic infections, which otherwise persist for life and can cause death."

According to Cox, the hepatitis C virus naturally mutates, or alters its genome, very rapidly. Its strains have two to three times more genetic variability, for example, than HIV, the virus that causes AIDS, and hepatitis C reproduces more than 100 billion times per day, 100 times faster than HIV. Compounding the problem, the infection is asymptomatic in the acute stage, making it less likely that diagnosis will be made early, when it is easiest to treat.

Conventional wisdom, the researchers say, was that the large numbers of mutations were simply random in the virus' ever-changing genome, but the new study suggests that Darwinian genetic selection is at play. That is, the virus' genome changes in ways that make it more reproductively "fit" in the face of each immune system it encounters, changing what is must to evade the immune system in one host, then restoring itself when the pressure is off.

What Ray's team found when the immune response weakens was that the virus naturally mutates toward a set of 3,000 common amino acids, what the researchers considered the virus' most preferred state. During the acute phase, Ray says, the virus is under severe pressure from the immune response and forced to drift away from the consensus sequence, using mutations to evade the immune response. However, the drift was reversible and, once the virus successfully evaded a particular immune cell, its amino acids reverted back to the consensus set.

To assess the genetic changes in the early stages of infection, the researchers decoded, or sequenced, the virus' genome, made up of RNA, which is very similar to the more widely known DNA that makes up the genome of most organisms. The RNA was gathered from eight newly infected patients in Baltimore, Md., all of whom were offered treatment and were participants in a larger study of infectious diseases in intravenous drug users. The sample group was unusual, allowing analyses before and during the early stages of infection. One patient self-recovered, while the rest proceeded to chronic infection.

Using advanced blood-sorting techniques, the Hopkins team extracted millions of immune system cells, including the systems' principal fighters, called T cells, from blood samples taken between 30 days and six months after infection, when the body's initial immune response kicks in and subsequently peaks.

Immune responses were mapped using a series of more than 500 overlapping synthetic peptides, or strings of amino acids whose code was already known. This allowed the researchers to compare changes observed in the RNA sequence to corresponding shifts in the body's immune response to the infection.

When specifically recognized by T cells, the peptides trigger production of interferon gamma, a protein that acts as a signal to many other immune cells to respond to a new infection. Reductions in the production of interferon gamma would indicate, the scientists say, that the immune system was weakening in its response to the virus' mutations.

After analyzing the genetic changes in the sites, called epitopes, where the T cells specifically bind to the virus, the researchers found no changes had occurred during the one year of follow-up in the one patient who self-recovered. However, in the remaining seven patients, there were changes in 69 percent of T-cell epitopes, showing that the virus had mutated at key locations necessary for chronic infection to proceed.

Additional analysis showed that changes in T-cell epitopes were 13 times more frequent than changes in the remaining genome of the virus. The researchers examined the binding ability of T cells obtained early in infection to recognize 10 viral peptides known to have changed during the first six months of infection. Eight showed severely reduced capacity to stimulate production of interferon gamma, offering confirmation that the virus was mutating to evade the immune system.

Analysis of the viral RNA in the blood of seven patients with chronic infections revealed that eight of 16 changes in genome matched to the consensus sequence, confirming the presence of selective evolutionary pressure toward restoration of an ancestral form of the virus.

In the second study, using blood samples collected in Cork, Ireland, the researchers compared the genetic makeup of the virus in 22 chronically infected women to the original strain that had infected them more than 20 years before. The women were among hundreds accidentally infected in 1977 by a blood product tainted with hepatitis C, providing the researchers with unique access to the source of the infection, which came from a single donor unaware of having the illness.

Using computer analysis techniques developed at Hopkins, the scientists mapped these changes against the genetic makeup of the women's immune response. The researchers found that when viral mutations were clustered in epitopes specific to each woman's immune system, the changes were directed away from the consensus sequence, suggesting immune escape. However, when mutations were clustered in epitopes that were not specific, the mutations were reversions back to the consensus sequence.

When the individual genome changes in each woman were mapped on a grid, each woman formed a unique cluster indicating individual, evolutionary selection. However, some of the changes were shared, suggesting convergence, which would not have occurred had the virus simply mutated at random.

"Our results raise the possibility that a hepatitis-C consensus sequence could be the best practical option for a vaccine," says infectious disease specialist David Thomas, M.D., a professor of medicine at Hopkins who served as senior author of the study of Irish women. "If we can focus vaccine development on the common genetic element in chronically infected patients, then we may be able to make a more effective vaccine."

Funding for these studies, which took place from January 2002 to January 2005, was provided by the National Institutes of Health, including the National Institute for Allergy and Infectious Disease, and the National Institute on Drug Abuse.

Other Hopkins investigators in this research were Timothy Mosbruger; Qing Mao, M.D., Ph.D.; Zhi Liu, M.D.; Xiao-Hong Wang, M.D.; Hung-Chih Yang; Xiao-Hang Wang, Ph.D., Dale Netski, Ph.D.; and Drew Pardoll, M.D. Co-investigators in the first study also included John Sidney, Ph.D., and Alessandro Sette, Ph.D., from the La Jolla Institute for Allergy and Immunology, in San Diego, Calif. Collaborators in the second study, conducted at Hopkins and at Cork University Hospital in Ireland, were Liam Fanning, Ph.D., and Kelizaeth Kenny-Walsh, M.D.

Hepatitis C is the leading cause of liver disease in the United States, causing an estimated 10,000 to 12,000 deaths each year. Hepatitis C is transmitted when blood and possibly other body fluids of an infected person enter another person, primarily through injection drug use, exposures in health care settings, from an infected mother to her baby during birth, and occasionally through sexual exposure. Symptoms of hepatitis C may not appear for years after infection, and diagnosis must be confirmed by blood tests. However, in addition to liver inflammation and tumors, earlier signs of infection are persistent flulike symptoms, including any combination of body aches, headaches, night sweats, loss of appetite, diarrhea, fatigue, rash, nausea and mild abdominal pain. Current treatments for hepatitis C involve weekly injections of pegylated interferon for one year, plus twice daily doses of oral ribavirin. While some patients recover on their own, with their immune system attacking the virus and clearing it from the body, most do not. Scientists have not yet determined why this happens in some patients and not in others.

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June 03, 2005

HCV Deaths to Triple in 10 Years

This report references the latest numbers from the Centers for Disease Control and the Wall Street Journal.

The numbers are sobering and give good reason to protect and support your liver as effectively as possible.

June 03, 2005

Hepatitis C deaths expected to triple in next 10 years in U.S.

The number of hepatitis C-related deaths in the United States will triple during the next 10 years, with as many as 30,000 Americans dying annually from problems caused by the disease, says the Centers for Disease Control and Prevention. The Wall Street Journal reports that about 8,000 to 10,000 Americans already die each year from the disease. CDC officials say that many of the people dying from hepatitis C-related complications contracted the virus between the 1960s and the 1980s. Because the virus typically lies dormant in the body for many years, those infected with HCV in the 1990s or later will begin to experience symptoms in the next decade.

HCV, a blood-borne virus, is transmitted through shared needles and blood transfusions, and less commonly through unprotected sex. HCV is a common coinfection among HIV-positive people, with as many as 25% of all HIV patients also infected with hepatitis. As many as 5 million Americans are currently infected with HCV; worldwide, there are an estimated 200 million people with hepatitis C. There is no vaccine to prevent HCV infections, and current treatments are effective for only about half of those patients who take them. New treatments currently in clinical trials might offer better results, experts say, but those drugs are still years away from Food and Drug Administration review and approval.

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May 16, 2005

Steatosis and Fibrosis

Reading selectively in this article gives us this tidbit: "Age, ADD, diabetes and increase of ALT seem to be the only independent factors associated with liver fibrosis progression.”

Among other things, this demonstrates the importance of keeping ALT levels as reduced as possible.

No Correlation Found Between Steatosis and Liver Fibrosis in HCV Genotype 1 Infection

Liver steatosis is generally regarded as a risk factor for chronic liver disease. Moreover, steatosis is considered in HCV-related chronic active hepatitis (CAH) as an adjunctive factor of progression and evolution of liver disease. In particular, steatosis is thought to be specifically related to the course of the disease in genotype 3a patients with CAH.

The aim of this study was to test the role of steatosis in liver damage (fibrosis) in a consecutive case-study of genotype 1b patients who have undergone liver biopsy because of an increase of serum ALT.

180 patients ( sex: M98/F82; median age: 51 range 17 - 68) underwent ultrasound examination and liver biopsy. Based on liver histology patients were divided according to steatosis into four classes: 1 (no steatosis), 2 (steatosis < 30%), 3 (steatosis 30 – 50 %), 4 (steatosis > 50 %).

Results:

·Histological Activity Index (HAI) was evaluated according to ISHAK’ s score.

·Median fibrosis value was S 2 (ranging 0 – 6; 23 patients showed liver cirrhosis) in all the 4 classes and no statistical significance was found between groups.

·Virological and epidemiologic characteristics, biochemical data, BMI, Apparent Duration of Disease (ADD) of all patients were recorded and statistical correlation checked.

·A univariate and multivariate analysis vs fibrosis were performed in all the patients and tested statistically significant only for age, ADD, diabetes and ALT (p< 0.00), but not for steatosis.

Conclusion

The authors conclude, “Steatosis does not seem to be an independent adjunctive risk factor of liver disease progression in CAH/genotype 1b HCV-infected patients….Age, ADD, diabetes and increase of ALT seem to be the only independent factors associated with liver fibrosis progression.”

05/02/05

Reference
M Persico and others. NO CORRELATION BETWEEN FAT LIVER ACCUMULATION AND LIVER FIBROSIS IN GENOTYPE 1B HCV RELATED CHRONIC LIVER DISEASE. Abstract 593. 40th EASL. April 13-17, 2005. Paris, France.

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May 05, 2005

Primary Concerns of HCV Patients

As researchers learn more about what issues are of most importance to patients they will be able to provide more relevant information and support.

What Are the Primary Concerns and Priorities of Individuals with Chronic Hepatitis C?

Counseling of patients with chronic hepatitis C infection is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counseling strategies and content.

Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them.

- The most common volunteered concerns of newly diagnosed patients
in decreasing order were:
- disease progression (27%)
- premature death (19%)
- infecting family members (13%) and
- side-effects of treatment (11%)

In decreasing order, prioritized concerns included:
- infecting family members
- development of liver cancer
- infecting others
- development of cirrhosis
- social stigma of having liver disease
- need for liver transplant, and
- loss of employment

The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, and modes of viral acquisition, and in the case of follow-up patients, duration of follow-up.

The authors conclude, "These results indicate that health care providers who focus counseling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection."

Reference
G Y Minuk and others. Patient concerns regarding chronic hepatitis C infections. Journal of Viral Hepatitis 12(1): 51-57. January 2005.

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April 26, 2005

HCV and Cirrhosis

Treatment of HCV in Cirrhotic Patients

By Marina Nunez, MD, PhD

Hepatitis C virus (HCV) infection is considered difficult to treat in patients with cirrhosis. In addition to diminished response to current anti-HCV therapies, these subjects with cirrhosis have a higher risk to develop decompensation of their liver disease and other complications.

Two studies presented at the 40th EASL meeting evaluated the efficacy and safety of treatment of patients with HCV-related liver cirrhosis with interferon (IFN)-based therapies [1,2].

In the Canadian study, these cirrhotic patients in early stage of disease were compared with non-cirrhotics [1]. There were no differences between both groups of patients in adverse events, nor in the proportion of patients undergoing dose modifications.

A trend to have lower responses among cirrhotic subjects compared to non-cirrhotics was observed for all genotypes, being more marked the differences in HCV-1-infected individuals. The authors suggest HCV-infected compensated cirrhotic patients can be successfully treated, and that higher responses may be achieved with optimal doses of RBV (1,000-1,200 mg/day).

In the study from the US, with more advanced liver disease, a higher number of subjects required discontinuation of the HCV treatment, and 3% experienced decompensation of liver disease [2].

Anemia requiring erythropoietin (EPO), neutropenia requiring G-CSF, and infections occurred in 50%, 16%, and 9% of subjects, respectively. Of notice, 15.6% of the patients were removed from the transplant list due to clinical improvement.

Therefore, treatment of HCV infection in subjects with advanced liver disease may be successful in a subset of well selected patients, especially in those carrying HCV genotypes other than 1. However, more complications arise among these subjects, and although treatment seems to be safe, their follow-up during therapy is very challenging.

04/25/05

References

1. S Lee and others. Peginterferon alfa-2a (40 kD) (PEGASYS®) plus ribavirin (COPEGUS®) in cirrhotic patients with chronic hepatitis C: results of a Canadian multicenter open-label expanded access programme. Abstract 576. 40th EASL. April 13-17, 2005. Paris, France.

2. J K Lim and others. Safety and efficacy of antiviral therapy in patients with decompensated cirrhosis associated with chronic hepatitis C infection. Abstract 579. 40th EASL. April 13-17, 2005. Paris, France.

To see this entire article go here: http://tinyurl.com/7p5vo

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April 25, 2005

How HCV Escapes Your Immune System

The following is from HIVandHepatitis.com. They publish some of the best technical articles on Hepatitis c available on the internet.

Replicative Homeostasis: A New Hypothesis to Explain How Viruses Such as HIV, HCV and HBV Persist and Escape Immune Controls

This article offers a new hypothesis concerning the persistence of certain viruses such as HIV, HCV and HBV and how they escape control by the immune system. In 40 days it has become the most downloaded article ever published by Virology Journal, an "Open Access" journal published by BioMed Central. This means that anyone can read, without charge, the articles appearing in it as soon as they are published.

The article explains why RNA viruses like Hepatitis C, HIV, West Nile / Yellow Fever / SARS / Ebola, etc persist, and demonstrates a mechanism of genotype/species maintenance, and of generating escape mutants in response to immune and other pressures. It explains why interferon may fail in some cases of hepatitis C and also explains the mechanism of antibody mediated disease enhancement. It also implies novel treatments for West Nile / HCV (and HIV, HBV, etc) might be possible, and describes what form they might take.

Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses (HIV), and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide.

These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s) by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical.

This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation--Replicative Homeostasis--is described.

Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses.

More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.

Note: This article uses highly technical language that many readers will find difficult to follow at times. Although the language is challenging for non scientists, it is worth the effort to read through the entire article, which offers compelling insights into the possible mechanisms of how HIV, HCV and HBV, among other viruses, persist.

You can access the article here: http://tinyurl.com/8nl26

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