Ribavirin for chronic hepatitis E virus infection in transplant recipients

N Engl J Med. 2014 Mar 20;370(12):1111-20. doi: 10.1056/NEJMoa1215246.

Abstract

Background: There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia.

Methods: We examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients). Ribavirin therapy was initiated a median of 9 months (range, 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range, 29 to 1200), which was equivalent to 8.1 mg per kilogram of body weight per day (range, 0.6 to 16.3). Patients received ribavirin for a median of 3 months (range, 1 to 18); 66% of the patients received ribavirin for 3 months or less.

Results: All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3). At the end of therapy, HEV clearance was observed in 95% of the patients. A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped. A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78%). A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period. A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response. Anemia was the main identified side effect and required a reduction in ribavirin dose in 29% of the patients, the use of erythropoietin in 54%, and blood transfusions in 12%.

Conclusions: This retrospective, multicenter study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Chronic Disease
  • Drug Administration Schedule
  • Female
  • Hepatitis E / drug therapy*
  • Hepatitis E virus / isolation & purification
  • Hepatitis E virus / physiology
  • Humans
  • Male
  • Middle Aged
  • Organ Transplantation*
  • Retrospective Studies
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Viral Load
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Ribavirin