Failure to achieve 2-log10 viral decrease in first four weeks of peg-IFNalpha-2b plus ribavirin therapy for chronic hepatitis C with genotype 1b and high viral titer is useful in predicting non-response: evaluation of response-guided therapy.

BACKGROUND/AIMS: To clarify clinical parameters predicting sustained viral response (SVR) during 48 weeks pegylated-interferon (peg-IFN)alpha-2b plus ribavirin therapy for Japanese patients with chronic hepatitis C [CH(C)] genotype 1b and high viral titers. METHODOLOGY: One hundred and fifty-one (151) patients receiving peg-IFNalpha-2b plus ribavirin therapy for 48 weeks were enrolled. SVR and clinical parameters were evaluated. The relationship between virological parameters (substitutions in the core and NS5A) and the degree of early viral decrease was also studied. RESULTS: Seventy (46.4%) patients achieved SVR (per protocol analysis). Negative predictive value (NPV) of <2-log10 decrease after 4 weeks of therapy for SVR was 78.0%; similar to that for failing to achieve early viral response (EVR) at 12 weeks (82.2%). CONCLUSIONS: Failure to achieve 2- log10 decrease in the first 4 weeks may be an important predictor of non-SVR during 48 weeks of peg-IFNalpha-2b plus ribavirin therapy; thus, therapeutic plans should be reassessed at that point.

Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C.

AIM: Elevation of alanine aminotransferase (ALT) levels during pegylated-interferon (peg-IFN) plus ribavirin therapy in patients with chronic hepatitis C [CHC] is a problem that cannot be disregarded. The aim of this study is to assess the frequency and to characterize clinical parameters of this phenomenon. METHODS: Two hundred and thirty-five (235) CHC patients with genotype 1b receiving peg-IFN α-2b plus ribavirin therapy were analyzed. Clinical parameters that may be associated with abnormal ALT values during treatment and therapy outcomes were evaluated statistically. One hundred and sixteen (116) patients treated with peg-IFN α-2a plus ribavirin were also included for partial analysis. RESULTS: Abnormal ALT values during treatment were observed in 23.0% of patients. It was observed in 14.5% of those with sustained virological response (SVR) and 17.8% of those with relapse, in whom viral clearance was observed during therapy. Multivariate logistic regression analysis revealed that pretreatment ALT values, therapy outcome, and body mass index (BMI) were significant factors related to abnormal ALT values during treatment. Abnormal ALT values during treatment became normal in SVR patients at 6 months after the completion of treatment, but not in NR (non-response) patients. Mean ALT values were significantly higher at some time points during treatment in patients treated with α-2a when compared to those treated with α-2b. CONCLUSION: Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.