title: Peg-IFN and ribavirin treatment for recurrence of genotype 2 and 3 hepatitis C after liver transplantation.
abstract: BACKGROUND
  Relapse of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. Tolerance for treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV) is suboptimal and withdrawals due to adverse events frequent. We sought to improve tolerance for treatment to improve outcome.
  
  
  METHODS
  We used concentration-guided RBV dosing to achieve an intended 10 μmol/L concentration with darbepoetin support in combination with peg-IFN alfa-2a, 180 μg for genotype 1 and 135 μg for genotype 2/3 to improve tolerance.
  
  
  RESULTS
  A total of 51/54 patients (94%) completed a full treatment course. In the per-protocol analysis 43% of patients (22/51) achieved sustained virological response (SVR), 82% with HCV genotype 2/3 and 22% with genotype 1, p = 0.0001. Patients with IL28B CC achieved SVR in 73% (8/11) and patients with non-CC in 33% (14/43), p = 0.016. Patients with mild fibrosis (fibrosis stage 1-2) achieved SVR in 56% (15/27), and patients with advanced fibrosis (fibrosis stage 3-4) in only 26% (7/27), p = 0.0267.
  
  
  CONCLUSIONS
  Concentration-guided RBV dosing with darbepoetin support substantially improves tolerance and offers high adherence to a full peg-IFN and RBV treatment course in patients with post-transplant HCV relapse. With this approach genotype 2 and 3 infections can be treated cost-effectively post-transplant. Genotype 1, IL28B non-CC genotype, and advanced fibrosis predicted a low SVR rate.
authors: Department of Medicine, Division of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital , Stockholm , Sweden.
authors: Malin
authors: M
authors: Ackefors
authors: Maria
authors: M
authors: Castedal
authors: Olav
authors: O
authors: Dahlgard
authors: Hans
authors: H
authors: Verbaan
authors: Henrik
authors: H
authors: Gjertsen
authors: Annika
authors: A
authors: Wernerson
authors: Ola
authors: O
authors: Weiland
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: HCV; chronic HCV; liver transplantation; peg-IFN; ribavirin