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 John 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 Lisa 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