Impairment of metabolic function in chronic hepatitis C is related to factors associated with resistance to therapy

OBJECTIVE: Liver disease causes a loss of hepatic function. and remission i s associated with improved functional hepatic mass. The object of the prese nt study was to investigate whether liver metabolic function assessed by an tipyrine clearance is related to other disease characteristics influencing response to therapy in chronic hepatitis C. METHODS: Patients (n = 96) received three different treatment regimens: one group received interferon alfa-2b for 48 wk; in a second group with mainta ined positive hepatitis C virus (HCV) RNA after 12 wk. interferon was combi ned for 36 wk with oral ribavirin: and patients who were relapsers or nonre sponders to a previous therapy with interferon alone received interferon al fa-2b plus ribavirin for 48 wk. RESULTS: Twenty-five patients (26%) showed sustained normalization of ALT l evels and negative HCV RNA 6 months after therapy. The response was more li kely to be sustained in patients with a genotype other than 1 (52.0% vs 15. 5% in patients with genotype 1. p < 0.001), and the percentage of sustained responders was higher among patients who demonstrated negativity of HCV RN A at the end of 4 wk of treatment (64% vs 13% without negativity, p < 0.001 ). Sustained response was associated with significantly lower baseline seru m ferritin (-46%. p < 0.01) and duration of infection (-33%, P < 0.01). Bas eline antipyrine clearance was higher in sustained responders than in nonre sponders (+19%, p < 0.05) and lower in genotype I patients than in those wi th a genotype other than 1 (-24% p < 0.05). Antipyrine clearance increased by 12% at the en of the 48-wk course of treatment among sustained responder s (+34% vs nonresponders, p < 0.001) and still remained elevated at the end of the follow-up (+35% vs nonresponders. p < 0.001). CONCLUSION: In summary, the present study shows that liver oxidative metabo lism is related to antiviral response rates and suggests that much of the e ffect is explained by viral genotype.