Objective: Our aim was to analyze the outcomes and the patterns of response to interferon treatment in patients with chronic hepatitis C using serum HCV RNA as the primary endpoint of therapy.
Methods: Seventy anti-HCV-positive patients were treated with 3 million U of interferon-alpha-2b thrice weekly for 24 wk and followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV RNA was measured by a reverse transcriptase-polymerase chain reaction method that has a sensitivity of < 100 viral copies per ml.
Results: The mean pretreatment HCV RNA was 2.8 +/- 2.2 x 10(6) viral copies per ml. Genotype 1 patients had significantly higher mean baseline viral titers than those with genotype 2 (p = 0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered virological complete responders (CR) to treatment. The remaining patients were HCV RNA positive at wk 48 and were considered nonresponders to therapy. There were two types of virological nonresponder patients, responder relapse (RR) and no response (NR). The mean baseline HCV RNA level was significantly lower in the virological CR patients (p = 0.0004). At wk 12 and 24 of interferon treatment, both the virological CR and RR patients had lower serum HCV RNA concentrations than the patients in the NR category (p = 0.0001), while at wk 48, only. the virological CR patients had undetectable HCV RNA when compared to the RR and NR patients (p = 0.04). Transient decreases in the HCV RNA titers of > or = 1 log in magnitude were observed in 49% of the NR patients, which rose to pretreatment levels either during or after interferon therapy.
Conclusions: Our findings indicate that measurement of serum HCV RNA precisely defined the responses to interferon therapy. Because the goal is to eliminate virus in patients with chronic hepatitis C infection, then HCV RNA should be used as the primary endpoint of treatment.