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AIM: To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C.METHODS: A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon (IFN) from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus (HCV) RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy. Patients who remained positive for HCV RNA at the end of IFN treatment were defined as resistant to IFN therapy. Sex, age, body mass index (BMI) (≥ 25 vs ＜ 25), complication of diabetes mellitus, serum leptin level (≥8.0 μg/L vs ＜8.0 μg/L),and the stage of liver fibrosis by needle biopsy (FL/F2 vs F3/F4) were examined.RESULTS: Sustained response was achieved in 33 patients (23.7%), while others failed to show a response to IFN therapy. Overall, the factors associated with sustained antiviral effects were HCV-RNA load, HCV genotype, serum leptin level, and stage of liver fibrosis evaluated by univariate analysis. BMI was not associated with any therapeutic effect of IFN. Multivariate analysis indicated that HCV-RNA load was a significant risk factor,but among the patients with low viremia (HCV-RNA ＜ 100 MU/L), leptin level was an independent risk factor for IFN resistance. Namely, a high level of serum leptin attenuated the effect of IFN on both male and female patients with low viremia.CONCLUSION: High serum leptin level is a negative predictor of response to antiviral treatment in chronic hepatitis C with low viremia.