With combination therapy, HCV RNA levels typically decrease rapidly on starting treatment and, in responders, become undetectable within 1 to 3 months ( Fig. 152-3 ). Serum aminotransferase levels become normal in most patients with a virologic response. In patients who relapse, HCV RNA and elevations in serum ALT levels reappear soon after therapy is stopped. In nonresponders, ALT levels may decrease and become normal, but HCV RNA remains detectable. The presence or absence of HCV RNA during therapy is the most accurate means of assessing response, and the most accurate end point in defining a beneficial response to treatment is absence of detectable HCV RNA (by a reliable and sensitive PCR technique) for at least 6 months after stopping therapy. A 6-month, post-treatment sustained virologic response is highly predictive of long-term remission and resolution of the liver disease and probably indicates eradication of the infection and cure of the disease.

In nonresponders, ALT levels may decrease and become normal, but HCV RNA remains detectable.