Am Fam Physician. 1998;57(8):1973-1974
Infection with hepatitis C virus often leads to chronic hepatitis, after which cirrhosis and hepatocellular carcinoma may develop. Currently, interferon-alfa is the only treatment, and it must be administered for more than six months to be effective. Many factors influence treatment outcome, including patient age and duration of infection, absence of cirrhosis, body weight, gamma-glutamyl transpeptidase levels, viral genotype and pre-treatment serum titer of hepatitis C RNA. However, these factors are not useful in predicting response to treatment in individual patients. Gavier and associates evaluated the predictive value of elimination of viremia after one month of treatment as a marker of successful treatment.
A total of 181 patients with chronic hepatitis C who had been treated with interferon-alfa for one year were included in the study. Laboratory values obtained before treatment showed alanine aminotransferase (ALT) concentrations 1.5 times above the normal range, positive results of antibody to hepatitis C virus testing and hepatitis C RNA serum testing, and histologic evidence of chronic hepatitis with or without cirrhosis. Treatment consisted of daily doses of interferon-alfa for two, three or four months, then three times a week for the remainder of the year. Median follow-up after treatment for all patients was 49 months. Patients were considered to have a sustained response if ALT levels remained within normal limits and serum HCV RNA levels were negative throughout the follow-up period. All other patients were considered nonresponders.
Fifty-one patients (28 percent) showed a sustained response to therapy. After one month of treatment, 68 of 132 tested patients had cleared hepatitis C virus RNA from serum. Among these 68 patients, one half showed a sustained response and one half were nonresponders. Of the 64 patients who remained viremic after one month of therapy, 61 were nonresponders, whereas only three had a sustained response. Transaminase levels obtained after the first and third months of therapy showed less significant association with the response. Several factors appear to be significantly associated with a higher probability of sustained response. Clearance of serum hepatitis C RNA after one month of treatment was the strongest independent predictor of sustained response. Negative viremia after one month of treatment resulted in a predicted probability of long-term response of 50 percent, with wide variability depending on age. Persistent viremia more accurately indicated a low probability of long-term response.
The authors conclude that early determination of viral status during therapy is the principal predictor of the final outcome of treatment. The negative predictive value of this measurement is quite high, although a small percentage of patients (less than 5 percent) would be misclassified as nonresponders. When viremia becomes negative, the probability of sustained response is likely to vary between 20 and 70 percent, depending on patient age. Withdrawal of treatment might be considered in patients who have not cleared hepatitis C virus RNA after one month, although in selected patients other potential benefits such as slower progression to cirrhosis and decreased risk of hepatocellular carcinoma should be considered.