Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection After Liver Transplantation: An Open-Label Study

doi:10.1053/j.gastro.2014.09.023

Gastroenterology

Volume 148, Issue 1, January 2015, Pages 100-107.e1

https://doi.org/10.1053/j.gastro.2014.09.023 Get rights and content

Under a Creative Commons license

open access

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.

Keywords

Hepatitis C Virus

Liver Transplantation

HCV Recurrence

Direct-Acting Antiviral Agents

Abbreviations used in this paper

HCC

hepatocellular carcinoma

HCV

hepatitis C virus

LLOQ

lower limit of quantification

MELD

model for end-stage liver disease

pTVR

post-transplantation virologic response

Cited by (0)

: Conflicts of interest These authors disclose the following: Michael P. Curry has received grants and performed research for Gilead, Salix, Merck, and MassBiologics, has served on the advisory board of Gilead, and has served as a consultant for Gilead; Xavier Forns has received grants and performed research for Merck and Roche, and has served as a consultant for AbbVie, Gilead, and Janssen; Raymond Chung has received grants and performed research for Gilead and MassBiologics, and has served as a consultant for AbbVie; Norah Terrault has received grants and performed research for Gilead, and has served on the advisory board of Gilead; Robert Brown Jr has received grants, performed research, and served as a consultant for Gilead; Jonathan Fenkel has served as a consultant for Gilead and Janssen; Fredric Gordon has received grants, performed research, served on the advisory board and as a consultant for Gilead; Jacqueline O’Leary has served as a consultant and a speaker for Gilead; Thomas Schiano has received grants and performed research for MassBiologics, Merck, Vertex, Biotest, and Gilead, and served on the advisory board for BMS, Idenix, and Janssen; Gregory Everson has received grants and performed research for Merck, Vertex, GSK, Genentech, BMS, Tibotic, GlobeImmune, Pfizer, Abbott, Conatus, Zymogenetics, PSC Partners, Boehringer Ingelheim, and Salix; served on the advisory boards of Genentech, Merck, HepQuant, PSC Partners, and HepC Connection; has served as a consultant for Genentech, BMS, Gilead, and Abbott; and holds a patent with PSC Partners; Eugene Schiff has received grants and performed research for Abbot, BMS, Gilead, Merck, Orasure Technologies, Roche, Vertex, Discovery Life Sciences, Beckman Coulter, Siemens, and MedMira, has served on the advisory boards of BMS, Gilead, Vertex, and Salix, and has been a consultant for Gilead and Merck; Alex Befeler has served on the advisory boards of Gilead and Janssen; Edward Gane has served on the advisory boards of Gilead, Novartis, Merck, Achillion, Idenix, and AbbVie, and has been a speaker for Gilead, Achillion, Novartis, and AbbVie; Sammy Saab has received grants and performed research for Gilead and Merck, has served as a consultant for Gilead, BMS, Genentech, Merck, AbbVie, Janssen, and Salix, has been a speaker for Gilead, BMS, Genentech, Merck, Janssen, and Salix, and owns stock in Gilead, BMS, Achillion, Vertex, J&J, and Salix; Dilip Moonka has received grants and performed research and been a speaker for Gilead; Nezam Afdhal has received grants and performed research for AbbVie, BMS, Gilead, Merck, and Vertex, has served on the advisory boards and as a consultant for Achillion, AbbVie, Merck, Gilead, Echosens, Glaxo Smith Kline, Vertex, Novartis, Boehringer Ingelheim, Ligand, Springbank, Medgenics, Kadmon, and Jannsen, owns stock in Springbank and Medgenics, and has served as the Editor of the Journal of Viral Hepatitis; John McHutchison, G. Mani Subramanian, William Symonds, Jill Denning, Lindsay McNair, Sarah Arterburn, and Evguenia Svarovskaia are current employees of Gilead Sciences. The remaining author discloses no conflicts.

: Funding Supported by Gilead Sciences.

: Author names in bold designate shared co-first authorship.