title: Influence of Ribavirin Serum Levels on Outcome of Antiviral Treatment and Anemia in Hepatitis C Virus Infection.
abstract: BACKGROUND
  Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered.
  
  
  METHODS
  The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1-4 infection, including 88 patients with available IL28b genotyping.
  
  
  RESULTS
  Mean ribavirin levels varied between 0.68-5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia.
  
  
  CONCLUSIONS
  While data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuntzen
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Sereina
authors.initials: S
authors.lastname: Kuhn
authors.affiliation: Department of Internal Medicine, Kantonsspital Baden, Baden, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuntzen
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute, University Zürich, Zürich, Switzerland.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.|Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000150:complications / Q000188:drug therapy*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D012367:RNA, Viral; D012372:ROC Curve; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood*; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda