Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation

被引：273

作者：

Charlton, Michael ^{[1
]}

Gane, Edward ^{[2
]}

Manns, Michael P. ^{[3
]}

Brown, Robert S., Jr. ^{[4
]}

Curry, Michael P. ^{[5
]}

Kwo, Paul Y. ^{[6
]}

Fontana, Robert J. ^{[7
]}

Gilroy, Richard ^{[8
]}

Teperman, Lewis ^{[9
]}

Muir, Andrew J. ^{[10
]}

McHutchison, John G. ^{[11
]}

Symonds, William T. ^{[11
]}

Brainard, Diana ^{[11
]}

Kirby, Brian ^{[11
]}

Dvory-Sobol, Hadas ^{[11
]}

Denning, Jill ^{[11
]}

Arterburn, Sarah ^{[11
]}

Samuel, Didier ^{[12
,13
]}

Forns, Xavier ^{[14
,15
]}

Terrault, Norah A. ^{[16
]}

机构：

[1] Mayo Clin, Rochester, MN 55905 USA

[2] Auckland City Hosp, Auckland, New Zealand

[3] Hannover Med Sch, Hannover, Germany

[4] Columbia Univ, New York, NY USA

[5] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[6] Indiana Sch Med, Indianapolis, IN USA

[7] Univ Michigan, Ann Arbor, MI 48109 USA

[8] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA

[9] NYU Med Ctr, New York, NY USA

[10] Duke Univ, Med Ctr, Durham, NC USA

[11] Gilead Sci Inc, Foster City, CA 94404 USA

[12] Hop Paul Brousse, AP HP, Ctr Hepatobiliaire, Villejuif, France

[13] Univ Paris 11, Villejuif, France

[14] IDIBAPS, Hosp Clin, Liver Unit, Barcelona, Spain

[15] CIBEREHD, Barcelona, Spain

[16] Univ Calif San Francisco, San Francisco, CA 94143 USA

来源：

GASTROENTEROLOGY | 2015年 / 148卷 / 01期

关键词：

Antiviral Agent; DAA; Clinical Trial; NS5B Polymerase Inhibitor; DRUG-DRUG INTERACTIONS; HCV GENOTYPE 1; ANTIVIRAL THERAPY; PLUS RIBAVIRIN; MULTICENTER; GRAFT; COMBINATION; INTERFERON; EFFICACY; DYSFUNCTION;

D O I：

10.1053/j.gastro.2014.10.001

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. METHODS: In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. RESULTS: Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%-82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. CONCLUSIONS: Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.

引用

页码：108 / 117

页数：10

共 29 条

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