11 Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University, New York, NY. 2 Division of Gastroenterology and Hepatology, University of California, San Francisco, CA. 3 Division of Gastroenterology and Hepatology, University of Colorado, Denver, Aurora, CO. 4 Division of Hepatology and Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 5 Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA. 6 Department of Gastroenterology and Hepatology, Northwestern University, Chicago, IL.
Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis.
The LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety.
Forty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation.
For LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.