Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study.

Abstract

BACKGROUND & AIMS:

Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward.

METHODS:

In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation.

RESULTS:

Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%).

CONCLUSIONS:

Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.

• Authors: Michael P Curry, Xavier Forns, Raymond T Chung, Norah A Terrault, Robert Brown Jr, Jonathan M Fenkel, Fredric Gordon, Jacqueline O'Leary, Alexander Kuo, Thomas Schiano, Gregory Everson, Eugene Schiff, Alex Befeler, Edward Gane, Sammy Saab, John G McHutchison, G Mani Subramanian, William T Symonds, Jill Denning, Lindsay McNair, Sarah Arterburn, Evguenia Svarovskaia, Dilip Moonka, Nezam Afdhal
• Journal: Gastroenterology (Gastroenterology) Vol. 148 Issue 1 Pg. 100-107.e1 (Jan 2015) ISSN: 1528-0012 [Electronic] United States
• PMID: 25261839 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• Biomarkers
• RNA, Viral
• Ribavirin
• Uridine Monophosphate
• Sofosbuvir

Topics

• Aged
• Antiviral Agents (adverse effects, therapeutic use)
• Biomarkers (blood)
• Carcinoma, Hepatocellular (diagnosis, mortality, surgery, virology)
• Drug Therapy, Combination
• Europe
• Female
• Genotype
• Hepacivirus (drug effects, genetics, pathogenicity)
• Hepatitis C (complications, diagnosis, drug therapy, mortality)
• Humans
• Liver Cirrhosis (diagnosis, mortality, surgery, virology)
• Liver Neoplasms (diagnosis, mortality, surgery, virology)
• Liver Transplantation (adverse effects, mortality)
• Male
• Middle Aged
• New Zealand
• Pilot Projects
• RNA, Viral (blood)
• Recurrence
• Ribavirin (adverse effects, therapeutic use)
• Sofosbuvir
• Time Factors
• Treatment Outcome
• United States
• Uridine Monophosphate (adverse effects, analogs & derivatives, therapeutic use)
• Viral Load
• Waiting Lists