Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).
Bibliographical noteFunding Information:
Received December 6, 2016; accepted May 9, 2017. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.29258/suppinfo. *These authors contributed equally to this work. **These authors should be considered co-senior authors. HCV-TARGET is an investigator-initiated study jointly sponsored by The University of Florida, Gainesville, FL (principal The University of North Carolina at Chapel Hill, Chapel Hill, NC (principal investigator M.W.F.), and is funded in part Squibb, Gilead, GlaxoSmithKline, Janssen, Kadmon, and Merck. Supported in part by National Institutes of Health DK066144, to M.W.F.) and the National Center for Advancing Translational Sciences (UL1TR001427, to D.R.N.).
Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29258 Potential conflict of interest: Dr. O’Leary is on the speakers’ bureau for Merck, AbbVie, and Gilead. Dr. Reddy advises and received grants from Gilead, Merck, AbbVie, Bristol-Myers Squibb, and Janssen. Dr. Sulkowski advises and received grants from AbbVie, Gilead, Merck, and Janssen. He advises Trek. Dr. Fried consults and received grants from AbbVie, Bristol-Myers Squibb, Gilead, and Merck. He consults and owns stock in Target. Dr. Galati is on the speakers’ bureau and received grants from Gilead and Merck. He received grants from Conatus and Beckman. Dr. Brown consults and received grants from Gilead and AbbVie. He consults for Bristol-Myers Squibb and Janssen. Dr. Terrault received grants from Gilead, Merck, AbbVie, and Bristol-Myers Squibb. Dr. Kuo advises and is on the speakers’ bureau for Gilead. Dr. Levitsky advises, is on the speakers’ bureau, and received grants from Novartis. He is on the speakers’ bureau for Gilead and Salix. Dr. Nelson received grants from AbbVie, Gilead, and Merck.
© 2017 by the American Association for the Study of Liver Diseases.