Predictors of a Sustained Beneficial Response to Interferon
Alfa Therapy in Chronic Hepatitis C
Interferon alfa was first reported to have beneficial effects in chronic hepatitis C in the mid-l980s,' effects that were subsequently verified in multiple randomized controlled trials performed in many countries throughout the ~o r l d . ~. ~ This agent was approved for use as therapy in chronic hepatitis C in 1991, the first and still the only approved therapy for a disease that accounts for at least 30% of chronic liver disease and cirrhosis in the United States.
In the several years since the licensing of interferon alfa for chronic hepatitis C, the enthusiasm for this therapy has been tempered by experience. A high proportion of patients have improvements in serum aminotransferases, hepatitis C virus (HCV) RNA levels, and hepatic histology during therapy, but only a small percentage have a long-term beneficial response.6 For instance, in a recent European multicenter trial using the standard regimen of interferon alfa recommended in the United States (3 million units thrice weekly for 6 months), the long-term response rate was only 14%.7
In our own experience from the Clinical Center of the National Institutes of Health, only 11 of 59 treated patients (19%) maintained a sustained response when assessed 1 to 5 years after therapy. Thus, many patients are treated but few have a long-term benefit.
Of course, if one could predict which patients would ultimately have a long-term beneficial response to interferon alfa therapy, one might treat only those whose likelihood of a response warranted the expense and discomforts of the 6 months of therapy. It is for this reason that clinical trials as well as most published large series of treatment usually include secondary analyses of predictive factors for a response; comparing the response to therapy according to pretreatment clinical, biochemical, histological, and virological features. Despite many differences in design of these studiesin types of interferon used, doses and drug regimens, patient populations, definitions of response, duration of follow-up, and serological and virological tests methods used-several predictive factors have been found repeatedly to be associated with a high likelihood of a Abbreviations: HCV, hepatitis C virus. From the Liver Diseases Section, Digestive Diseases Branch, and the Epide-