Hepatic hepatitis C virus RNA as a predictor of a long-term response to interferon-alpha therapy

To identify predictors of a long-term response to interferon-alpha therapy in chronic hepatitis C and to determine whether hepatitis C virus (HCV) was eradicated in patients with chronic hepatitis C who had a long-term response to therapy.

A retrospective analysis.

In- and outpatient liver clinic of a municipal hospital in Japan.

47 patients with chronic hepatitis C who responded to interferon-alpha were divided into two groups: 22 patients with a long-term response (serum aminotransferase levels remained normal for > 1 year after therapy) and 25 patients with a short-term response (serum aminotransferase levels increased again after therapy).

Genotyping of HCV, titers of HCV RNA in liver and serum samples (using the reverse transcriptase-polymerase chain reaction), histologic activity index, and liver histologic tests during and 1 year after therapy.

Among the 22 long-term responders, HCV RNA was no longer detectable in liver and serum samples of 21 (95%) at the end of therapy and remained undetectable in the serum of 20 (91%) and in the liver of 19 (86%) 1 year after therapy. Liver histologic tests improved substantially immediately after therapy and 1 year after therapy in the long-term responders; however, 18 (82%) of these patients still had mild, chronic hepatitis. Among the 25 short-term responders, HCV RNA was still detected in the liver of 19 (76%) and in the serum of 9 (36%) at the end of therapy. Multivariate logistic regression analysis showed that the persistent presence of hepatic HCV RNA at the end of therapy was the strongest predictor of relapse.

These findings suggest that HCV infection was eradicated in most of the long-term responders to interferon-alpha therapy because HCV RNA could no longer be detected in their serum and liver samples and because a significant improvement gradually occurred in their liver histologic results. The persistent presence of hepatic HCV RNA at the end of therapy was the most important predictor of relapse.