Daclatasvir and sofosbuvir treatment of decompensated liver disease or post‐liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real‐world cohort. Issue 4 (27th February 2018)

• Record Type: Journal Article
• Authors: Kwo, Paul; Fried, Michael W.; Reddy, K. Rajender; Soldevila‐Pico, Consuelo; Khemichian, Saro; Darling, Jama; Zamor, Phillippe J.; Napoli, Andrew A.; Anduze‐Faris, Beatrice; Brown, Robert S.
• Is Part Of: Hepatology communications. Volume 2:Issue 4(2018)
• Page Start: 354
• Page End: 363
• Publication Date: 2018-02-27
• Subjects: Hepatology -- Periodicals; Liver -- Diseases -- Periodicals; Liver Diseases; Gastroenterology; Periodicals; Fulltext; Internet Resources; Periodicals; 616.36
• DOI: 10.1002/hep4.1156
• Languages: English
• ISSNs: 2471-254X

Abstract

Abstract : Seventy‐seven patients with a life expectancy <1 year due to hepatitis C‐related decompensated cirrhosis (Child‐Pugh C) or recurrent hepatitis C with advanced fibrosis following a liver transplant were treated with daclatasvir plus sofosbuvir, with or without ribavirin, for 24 weeks in a US expanded access program. Twelve weeks after treatment, a sustained HCV virologic response was observed in 84% overall (90% transplant group; 62% decompensated group) by modified intention‐to‐treat analysis, and 96% (97% transplant; 89% decompensated) as‐observed, with 6 deaths and 30 serious adverse events primarily related to advanced liver disease. The combination of daclatasvir and sofosbuvir (with or without ribavirin) was efficacious and generally well tolerated in this group of real‐world patients with advanced and life‐threatening hepatitis C disease. Abstract : We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child‐Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12‐month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks. Sustained virologic response (SVR) at posttreatment week 12 (SVR12) was measured. Assessments adhered to local standards. One patient (prior Child‐Pugh class C who improved to class B) enrolled by exemption was included in the overall data but not the class C cohort efficacy/safety data. Of the 77 treated patients, including 62 liver transplant recipients (genotype 1, n = 43, 69%; genotype 3, n = 16, 26%) and 14 patients with Child‐Pugh class C cirrhosis (genotype 1, n = 4, 29%; genotype 3, n = 10, 71%), 63 (82%) completed treatment. SVR12 rates by modified intention‐to‐treat analysis (excluding nonvirologic failures lost to follow‐up and withdrawal [consent/no reason]) in the overall, liver transplant, and Child‐Pugh class C cohorts were 84% (n = 64/76), 90% (n = 56/62), and 62% (n = 8/13), respectively. Rates increased to 96% (n = 64/67), 97% (n = 56/58), and 89% (n = 8/9), respectively, in patients with available virologic data (including early discontinuations); 22/23 patients with genotype 3 (96%) achieved SVR12. Single cases of virologic nonresponse and relapse (both in liver transplant recipients with genotype 1) and viral breakthrough (Child‐Pugh class C; genotype 3) occurred. Six patients died, 10 had adverse events leading to discontinuation, and 30 experienced serious adverse events. Conclusion: Daclatasvir plus sofosbuvir, with/without ribavirin, provided high SVR12 rates and was generally well tolerated in patients with life‐threatening disease and high unmet needs. ( Hepatology Communications 2018;2:354‐363)