title: Real-world experience with daclatasvir plus sofosbuvir ± ribavirin for post-liver transplant HCV recurrence and severe liver disease.
abstract: Optimizing therapy of post-transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in patients with post-liver transplant recurrence in a real-world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60 mg plus SOF 400 mg once daily for 24 weeks; RBV use/shorter treatment duration was at physicians' discretion. Patients (N = 87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis. Sustained virologic response at post-treatment week 12 (SVR12) was 94% (80/85) in a modified intention-to-treat analysis: 95% (58/61) without RBV and 92% (22/24) with RBV, with no virologic failures. SVR12 was 100% (80/80) in an as-observed analysis excluding five nonvirologic failures. Four patients (5%) discontinued therapy for adverse events (AEs); 16 (18%) experienced serious AEs. One patient died on treatment and five during follow-up. Most AEs were associated with advanced liver disease and unrelated to therapy. No clinically significant drug-drug interactions were observed. DCV + SOF ± RBV was well tolerated and achieved high SVR12 (94%) in patients with post-transplant HCV recurrence, including patients with severe liver disease.
authors.affiliation: Universitätsklinikum Essen, Essen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
authors.affiliation: Universitätsklinikum der Johann Wolfgang Goethe Universität, Frankfurt, Germany.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Welzel
authors.affiliation: Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.affiliation: Gastroenterologisch-Hepatologisches Zentrum Kiel, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hinrichsen
authors.affiliation: Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: Universitätsklinikum Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Medical University of Vienna, Vienna, Austria.|Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Akin
authors.initials: A
authors.lastname: Inderson
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Jimenez-Exposito
authors.affiliation: Universitätsklinikum der Johann Wolfgang Goethe Universität, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D058625:End Stage Liver Disease / Q000209:etiology / Q000601:surgery*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage; D000069474:Sofosbuvir / Q000008:administration & dosage; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: Decompensated; HCV therapy; fibrosing cholestatic hepatitis; liver transplant