title: High-Dose Ribavirin Enhances Early Virological Response in Hepatitis C Genotype 1-Infected Patients.
abstract: 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 μmol/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.
authors: *Division of Infectious Diseases, Department of Internal Medicine, Karolinska Institutet, Karolinska University Hospital; and †Division of Clinical Pharmacology, Department of Medical Laboratory Sciences, Karolinska Institutet, Stockholm, Sweden.
authors: Karin
authors: K
authors: Lindahl
authors: Erika
authors: E
authors: Hörnfeld
authors: Lars
authors: L
authors: Ståhle
authors: Tony
authors: T
authors: Carlsson
authors: Ola
authors: O
authors: Weiland
authors: Åsa
authors: Å
authors: Parke
authors: Robert
authors: R
authors: Schvarcz
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D060085:Coinfection; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons