Factors That Affect Success of Interferon-based Treatment for Hepatitis C

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Factors That Affect Success of Interferon-based Treatment for

Hepatitis C

A new study on predicting outcomes of standard treatment for

hepatitis C virus (HCV) infection found that a number of factors

influenced responses, including the form of the interferon given.

However, for some HCV genotypes, few of these factors play a role.

The results of this study appear in the July 2007 issue of

Hepatology, the official journal of the American Association for the

Study of Liver Diseases (AASLD),

published by Wiley & Sons. Hepatology is available online via

Wiley InterScience at

http://www.interscience.wiley.com/journal/hepatology.

About 4 million people in the U.S. have been infected with HCV, and

more than 3 million have chronic HCV infection. Hepatitis C accounts

for approximately 40% of all chronic liver disease and is the most

frequent indication for liver transplants.

The current standard of care for chronic HCV infection is the

combination of pegylated interferon alfa plus ribavirin, but this

treatment can be difficult to tolerate. Many people experience

adverse side effects that may include fatigue, flu-like symptoms,

depression, fever, and anemia. These symptoms can be severe enough to

cause patients to discontinue treatment.

Researchers led by Backus, MD, of the Center for Quality

Management in Public Health located at the Veterans Affairs (VA) Palo

Alto Health Care System in Palo Alto, CA, conducted a large

retrospective study to analyze predictors of

sustained virological response (SVR), or undetectable virus in the

blood 6 months after finishing treatment.

The researchers used a time frame of 3 months or later to determine

SVR, because a previous study showed that 98% of relapses occur

within 3 months of stopping treatment. The study included 5944

predominantly male patients receiving care at VA medical facilities.

The researchers were able to identify several independent predictors

of achieving SVR after treatment. " In many of the previous trials

only a few of these factors were identified, " they stated. " The

expanded range of predictors may assist clinicians and patients in

more accurately assessing the likelihood of an SVR and thus in making

more informed treatment decisions. "

The results confirmed previous trials that identified independent

several factors that predicted sustained response, including:

· Low levels of HCV in the blood;

· Absence of cirrhosis;

· HCV genotypes other than genotype 1;

· Elevated levels of the liver enzyme ALT.

They also confirmed significantly lower SVR rates among African-

Americans compared with Caucasians, and among patients who had not

responded to prior treatment with conventional (non-pegylated)

interferon.

The results provide new information indicating that the form of

pegylated interferon may affect the likelihood of SVR: Patients

treated with pegylated interferon alfa-2a (Pegasys) were 40% more

likely to achieve SVR than those treated with pegylated interferon

alfa-2b (PegIntron). The 2 forms differ in pharmacokinetic

properties, side effects, and method of determining dosage.

In addition, the study identified low baseline blood cholesterol as a

negative predictor of SVR. " Low cholesterol may indicate more severe

liver disease and subsequent reduced treatment response, " the

researchers noted.

In this study, 80% of the participants had HCV genotype 1. Few of the

significant independent predictors of SVR in patients with this

genotype influenced the sustained response rate for patients with HCV

genotype 2, and even fewer did so for those with genotype 3.

These results suggest that patients with genotype 2 are more likely

to respond to hepatitis C treatment than those with genotype 3, and

that SVR predictors differed between these 2 genotypes, as well as

from those for genotype 1.

" Our findings serve as a reminder that response rates in routine

medical practice may be lower than those in clinical trials, " the

researchers stated.

This may be due to the fact that a substantial percentage of the

study patients would have been excluded from clinical trials for

having factors that negatively predict SVR. The study also showed

higher treatment discontinuation rates than in clinical trials,

possibly because patients in trials are generally extremely motivated

and usually agree to continue treatment regardless of their response

or lack thereof.

The researchers concluded that, " with the demonstrated efficacy of

pegylated interferon/ribavirin against HCV, it is increasingly

important to understand the predictors of response to this treatment.

Just as SVR rates differ substantially by genotype, so too do the

significant SVR predictors. "

This research was supported by the U.S. Department of Veterans

Affairs.

07/17/07