Shindo and colleagues [1] wonder whether patients who have chronic hepatitis C and a long-term biochemical response to interferon but remain positive for hepatitis C virus (HCV) RNA in the serum or liver will have a relapse later.

We are following a cohort of 62 long-term responders from two trials that enrolled 425 patients (264 [62%] had chronic hepatitis and 161 [38%] had cirrhosis). These patients were treated for 6 to 12 months with interferon- 2b or interferon- n1 at 5 to 10 MU three times a week. The long-term responders consisted of 41 men and 21 women (mean age, 43.6 years; range, 20 to 62 years). Fifty-five patients had chronic hepatitis and 7 had cirrhosis. All patients were positive for HCV RNA (according to nested polymerase chain reaction on the 5' untranslated region of HCV) before therapy, and all were checked every 3 months after interferon therapy was discontinued. Hepatitis C virus RNA has been retested in all patients at least 6 months after the end of therapy (mean, 34.4 months; range, 6 to 72 months). Thirty-five patients had a second liver biopsy 1 year after interferon was stopped. We never saw a late relapse of alanine aminotransferase in the long-term responders during follow-up, regardless of the initial histologic findings. The relative frequency of viral persistence, as shown by HCV RNA in serum, was significantly higher in patients with cirrhosis (4 of 7 patients [57%]) than in those with chronic hepatitis (4 of 55 patients [7%]) (P = 0.001). Examination of the second liver biopsy specimens showed a profound decrease in necroinflammatory activity (range of hepatitis activity index scores, 10.8 ± 4.6 to 4.3 ± 2.6); no significant differences were seen for patients who were still HCV RNA positive after interferon therapy. No major disease events occurred during the entire follow-up period.

We conclude that for patients treated with interferon-, the likelihood of becoming a long-term responder is 1 in 5 for patients with chronic hepatitis and 1 in 25 for patients with cirrhosis. Hepatitis C virus is not eradicated in all long-term responders, and the chances of losing HCV RNA are especially low for patients with cirrhosis. The sustained biochemical response appears to be long-lasting even when the virus continues to replicate.