Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study

Gastroenterology. 2007 May;132(5):1746-56. doi: 10.1053/j.gastro.2007.03.041. Epub 2007 Mar 24.

Abstract

Background & aims: Recurrence of hepatitis C virus (HCV) infection is a relevant problem of liver transplantation programs. We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients.

Methods: Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n = 54) were randomized to no treatment (group A, n = 27) or peginterferon alfa-2b/ribavirin for 48 weeks (group B, n = 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n = 27). All patients (n = 81) underwent a liver biopsy at baseline and after follow-up; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients.

Results: Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed > or =1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P = .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P = .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] =3.7, 95% confidence interval [CI] 1.3 to 10, P = .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P = .01; respectively).

Conclusions: Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.

Trial registration: ClinicalTrials.gov NCT00383864.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biopsy
  • Darbepoetin alfa
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Erythropoietin / analogs & derivatives
  • Erythropoietin / therapeutic use
  • Female
  • Hematinics / therapeutic use
  • Hepatitis C / etiology*
  • Hepatitis C / physiopathology
  • Hepatitis C / prevention & control*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Liver / blood supply
  • Liver / pathology
  • Liver / physiopathology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / methods
  • Male
  • Middle Aged
  • Polyethylene Glycols
  • Portal Pressure / physiology
  • Recombinant Proteins
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Secondary Prevention

Substances

  • Antiviral Agents
  • Hematinics
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Erythropoietin
  • Darbepoetin alfa
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b

Associated data

  • ClinicalTrials.gov/NCT00383864