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

Abstract

OBJECTIVE: Liver disease causes a loss of hepatic function, and remission is associated with improved functional hepatic mass. The object of the present study was to investigate whether liver metabolic function assessed by antipyrine 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 maintained positive hepatitis C virus (HCV) RNA after 12 wk, interferon was combined for 36 wk with oral ribavirin; and patients who were relapsers or nonresponders to a previous therapy with interferon alone received interferon alfa-2b plus ribavirin for 48 wk. RESULTS: Twenty-five patients (26%) showed sustained normalization of ALT levels and negative HCV RNA 6 months after therapy. The response was more likely 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 RNA at the end of 4 wk of treatment (64% vs 13% without negativity, p < 0.001). Sustained response was associated with significantly lower baseline serum ferritin (−46%, p < 0.01) and duration of infection (−33%, p < 0.01). Baseline antipyrine clearance was higher in sustained responders than in nonresponders (+19%, p < 0.05) and lower in genotype 1 patients than in those with a genotype other than 1 (−24%, p < 0.05). Antipyrine clearance increased by 12% at the end of the 48-wk course of treatment among sustained responders (+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 metabolism is related to antiviral response rates and suggests that much of the effect is explained by viral genotype.