Impairment of metabolic function in chronic hepatitis C is related to factors associated with resistance to therapy
F. Jorquera, M. Almar, J.L. Olcóz, V. Díaz-Golpe, A. García-Fernández, J. González-Gallego
American Journal of Gastroenterology: 2001, 96: 2456-2461

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 for 48 weeks interferon alfa-2b; in a second group with maintained positive HCV RNA after 12 weeks, interferon was combined for 36 weeks with oral ribavirin; patients who were relapsers or nonresponders to a previous therapy with interferon alone received for 48 weeks interferon alfa-2b plus ribavirin. Results: 25 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 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 that demonstrated negativity of HCV RNA at the end of 4 weeks 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 genotype other than 1 (-24%; p <0.05). Antipyrine clearance increased by 12% at the end of the 48-week 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). Conclusions: 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.

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