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

被引:254
作者
Curry, Michael P. [1 ]
Forns, Xavier [2 ,3 ]
Chung, Raymond T. [4 ]
Terrault, Norah A. [5 ]
Brown, Robert, Jr. [6 ]
Fenkel, Jonathan M. [7 ]
Gordon, Fredric [8 ]
O'Leary, Jacqueline [9 ]
Kuo, Alexander [10 ]
Schiano, Thomas [11 ]
Everson, Gregory [12 ]
Schiff, Eugene [13 ]
Befeler, Alex [14 ]
Gane, Edward [15 ]
Saab, Sammy [16 ]
McHutchison, John G. [17 ]
Subramanian, G. Mani [17 ]
Symonds, William T. [17 ]
Denning, Jill [17 ]
McNair, Lindsay [17 ]
Arterburn, Sarah [17 ]
Svarovskaia, Evguenia [17 ]
Moonka, Dilip [18 ]
Afdhal, Nezam [1 ]
机构
[1] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA
[2] Inst Invest Biomed August Pi & Sunyer, Liver Unit, Hosp Clin, Barcelona, Spain
[3] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
[4] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA
[5] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA
[6] Columbia Univ, Ctr Liver Dis & Transplantat, New York, NY USA
[7] Thomas Jefferson Univ Hosp, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA
[8] Lahey Clin Fdn, Burlington, MA USA
[9] Baylor Univ, Med Ctr, Dallas, TX USA
[10] Univ Calif San Diego, La Jolla, CA 92093 USA
[11] Mt Sinai Sch Med, New York, NY USA
[12] Univ Colorado, Sect Hepatol, Denver, CO 80202 USA
[13] Univ Miami, Ctr Liver Dis, Miami, FL USA
[14] St Louis Univ, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA
[15] Auckland City Hosp, New Zealand Liver Transplant Unit, Auckland, New Zealand
[16] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA
[17] Gilead Sci Inc, Foster City, CA 94404 USA
[18] Henry Ford Hlth Syst, Gastroenterol, Detroit, MI USA
关键词
Hepatitis C Virus; Liver Transplantation; HCV Recurrence; Direct-Acting Antiviral Agents; TREATMENT-NAIVE PATIENTS; HEPATITIS-C INFECTION; ANTIVIRAL THERAPY; PHASE-2; TRIAL; KINETICS; TOLERABILITY; CIRRHOSIS; ALPHA-2A; FUTURE; CELLS;
D O I
10.1053/j.gastro.2014.09.023
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 non-function 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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收藏
页码:100 / U519
页数:9
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