Hepatitis C virus infection often leads to chronic hepatitis, which may progress to cirrhosis and/or hepatocellular carcinoma. Interferon alfa is the only currently known effective therapy, but it requires a minimum of six months of treatment, and only a small percentage of patients receive long-term benefits. Although several factors, including age, absence of cirrhosis, viral genotype and other variables that influence treatment outcome have been identified, a better predictor of response to treatment would be useful. Gavier and associates analyzed viral status after initiation of interferon therapy as a predictor of treatment outcome.
One hundred eighty-one patients with hepatitis C virus infection were followed for a median of 49 months to find the predictive value of eliminating viremia one month into treatment. The study subjects, who had elevated alanine aminotransferase (ALT) levels and histologic evidence of chronic hepatitis, had been treated with a one-year course of interferon alfa therapy and were followed up with measurements of ALT and serum hepatitis C virus RNA concentrations. A sustained response—normal liver function tests—was obtained in 51 of the patients (28 percent). Of 132 patients who had been tested for hepatitis C virus RNA after one month of treatment, hepatitis C virus RNA was cleared from serum in 68. Of these 68 patients, one half had a sustained response, and one half were nonresponders. Among the 64 subjects who remained viremic after one month of therapy, only three (4.7 percent) responded to treatment.
Follow-up demonstrated that variables associated with a higher probability of response to treatment include younger age, lower body mass, higher pretreatment levels of ALT, lower pretreatment levels of gamma-glutamyl trans-peptidase, absence of cirrhosis, clearance of hepatitis C virus RNA at the first or third month of treatment, and lower pretreatment viral loads. The only procedure useful in isolated cases appears to be the hepatitis C virus RNA count after one month of treatment. Clearance of hepatitis C virus RNA seemed to have moderate predictive value for sustained response, while persistence of hepatitis C virus RNA in serum at one month of treatment appears to much more accurately predict non-response.
The authors conclude that early monitoring of hepatitis C virus RNA during interferon treatment may help the physician make therapeutic decisions in individual patients. When hepatitis C virus RNA remains positive at one month of treatment, the probability of a sustained response to interferon therapy is very low (less than 5 percent). When viremia becomes negative, the probability of sustained response averages 50 percent, varying from 70 percent to 20 percent depending on age. Withdrawal of interferon therapy in patients who have persistent hepatitis C virus RNA counts at one month of treatment should be considered. In selected patients, continuation of therapy in the face of persistent viremia might be appropriate for other treatment benefits such as slowed progression of cirrhosis and decreased risk of hepatocellular carcinoma.