High-Dose Ribavirin Enhances Early Virological Response in Hepatitis C Genotype 1-Infected Patients

作者：Lindahl Karin^*; Hornfeld Erika; Stahle Lars; Carlsson Tony; Weiland Ola; Parke Asa; Schvarcz Robert

来源：Therapeutic Drug Monitoring, 2015, 37(6): 745-750.

DOI：10.1097/FTD.0000000000000210

• hepatitis C
• nonresponders
• ribavirin
• pharmacokinetics

Background:The aim of the study was to investigate whether patients with a previous nonresponse to standard of care treatment with ribavirin dosed according to body weight would respond to a high individualized dose of concentration-monitored ribavirin.Methods:Previous nonresponders to standard of care treatment with peginterferon (peg-IFN) and ribavirin were included. Ribavirin was dosed aiming at a plasma concentration of >15 mol/L. The initial ribavirin dose was calculated from a formula based on renal function and body weight. Erythropoietin treatment was started 2 weeks before antiviral therapy.Results:Twenty patients (16 men and 4 women) with a mean age of 52 years were included. Sixty percent had advanced fibrosis. Eighty percent of patients achieved an early viral response, and 60% were negative for hepatitis C virus ribonucleic acid (HCV RNA) at treatment week 24. High-dose ribavirin resulted in a significantly increased HCV RNA drop at week 12 (mean: 3.13 versus 2.05 IU/mL; P < 0.001). Nine patients were negative for HCV RNA at the end of treatment, and 1 achieved sustained viral response. The final steady-state daily dose of ribavirin varied from 1400 to 4400 mg. Hemoglobin levels decreased during treatment, mean Hb 163, 134, and 110 g/L at week 0, 4, and 12, respectively. Two patients received blood transfusions. No other severe adverse events were recorded.Conclusions:An individualized high ribavirin dose resulted in a more pronounced early viral HCV RNA decline than a standard-dose ribavirin scheme. This regime is safe provided that close monitoring of anemia is undertaken and that treatment with erythropoietin is given.

• 出版日期2015-12