Efficacy of interferon monotherapy to 394 consecutive naive cases infected with hepatitis C virus genotype 2a in Japan: therapy efficacy as consequence of tripartite interaction of viral, host and interferon treatment-related factors

Background/Aims: The mechanism of variable response to interferon (IFN) monotherapy in patients infected with HCV genotype 2a is still unclear. Here we investigated the response in a large group of patients infected with genotype 2a. Methods: We evaluated 394 consecutive non-cirrhotic naive patients infected with genotype 2a who received IFN monotherapy for 24 weeks, including initial aggressive induction therapy. Of these, 97 were also evaluated for early viral kinetics in serum and treatment efficacy. Results: The overall sustained response (SR) rate was 68.3% (viral load <1.0 Meq/ml (82.4%); ≥1.0 (52.4%)). Multivariate analysis identified five independent factors associated with SR; viral load <1.0 Meq/ml, total IFN dose ≥700 million units, hepatocyte steatosis none or mild, albumin ≥3.9 g/dl, and alanine aminotransferase ≥75 IU/l. The kinetic study showed that serum viral clearance at ≤1 week was the best predictor of SR, and persistence at ≥ 4 weeks was a predictor of non-SR. Conclusions: Our study suggests that viral, host and IFN treatment-related factors determine the response to IFN monotherapy in patients infected with HCV genotype 2a. Further, we report that IFN monotherapy is very effective for patients with genotype 2a, especially for those with low viral load; and that early viral kinetics is useful as a predictor of the response.