ROCHESTER, MN -- July 2, 2007 -- A new study on predicting outcomes of standard treatment for hepatitis C virus (HCV) infection found that a number of factors impacted responses, including the form of the interferon given. However, for some genotypes of the disease, 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).
Over 3 million people in the United States have chronic HCV infection, which accounts for approximately 40% of all chronic liver disease and is the most frequent indication for liver transplants. The current standard of care for HCV is the combination of pegylated interferon alfa (PEG-INF) and ribavarin, but this treatment can be difficult to tolerate. Many patients have side effects that include fatigue, flu-like symptoms, depression, fever, and anemia. These can be severe enough to cause these patients to discontinue treatment.
Led by Lisa I. Backus, of the Center for Quality Management in Public Health located at the Veterans Affairs Palo Alto Health Care System in Palo Alto, California, researchers conducted a large retrospective study to analyze predictors of sustained virologic response (SVR), defined as undetectable virus in the blood 6 months after finishing treatment. For this study, the researchers used a time frame of 3 months or later to determine an SVR, because a previous study showed that 98% of relapses occur within 3 months of stopping treatment. The study included 5,944 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 state. "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 low levels of HCV in the blood, absence of cirrhosis, genotype other than genotype 1, and elevated levels of the liver enzyme ALT as independent predictors of SVR. They also confirmed significantly lower SVR rates among African Americans compared with Caucasians and among patients who had not responded to prior non-pegylated interferon. The results provided new information indicating that the PEG-INF form may affect the likelihood of an SVR: Patients treated with PEG-INF 2A (as opposed to 2B) were 40% more likely to have an SVR. The two forms differ in pharmacokinetic properties, side effects, and method of determining dosage. In addition, the study identified low baseline cholesterol as a negative predictor of an SVR. "Low cholesterol may indicate more severe liver disease and subsequent reduced treatment response," the researchers note.
Patients included in the study were 80% genotype 1, but few of the significant SVR predictors for this genotype impact the rate for genotype 2 patients and even fewer do so for genotype 3 patients. The results suggest that genotype 2 patients are more likely to respond to HCV treatment than genotype 3 patients, and that SVR predictors differed between these two 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 state. This may be due to the fact that a substantial percentage of the study patients would have been excluded from clinical trials for factors that negatively predict an SVR, and the study 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.
The researchers conclude that "with the demonstrated efficacy of PEG-INF/ribavarin 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."
SOURCE: John Wiley & Sons, Inc.
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