Michael P Curry1, Xavier Forns2, Raymond T Chung3, Norah A Terrault4, Robert Brown5, Jonathan M Fenkel6, Fredric Gordon7, Jacqueline O'Leary8, Alexander Kuo9, Thomas Schiano10, Gregory Everson11, Eugene Schiff12, Alex Befeler13, Edward Gane14, Sammy Saab15, John G McHutchison16, G Mani Subramanian16, William T Symonds16, Jill Denning16, Lindsay McNair16, Sarah Arterburn16, Evguenia Svarovskaia16, Dilip Moonka17, Nezam Afdhal18. 1. Transplant Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: mcurry@bidmc.harvard.edu. 2. Liver Unit, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. 3. GI Unit, Massachusetts General Hospital, Boston, Massachusetts. 4. Division of Gastroenterology, University of California San Francisco, San Francisco, California. 5. Center for Liver Diseases and Transplantation, Columbia University, New York, New York. 6. Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 7. Liver Transplantation & Hepatology, Lahey Clinic, Burlington, Massachusetts. 8. Transplant Hepatology, Baylor University Medical Center, Dallas, Texas. 9. Liver Transplantation, University of California, San Diego, La Jolla, California. 10. Liver Diseases, Mount Sinai School of Medicine, New York, New York. 11. Section of Hepatology, University of Colorado, Denver, Colorado. 12. Center for Liver Disease, University of Miami, Miami, Florida. 13. Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri. 14. New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand. 15. Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 16. Gilead Sciences, Foster City, California. 17. Gastroenterology, Henry Ford Health System, Detroit, Michigan. 18. Transplant Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
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.
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.
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