Tolerability and effectiveness of sofosbuvir and simeprevir in the post-transplant setting: systematic review and meta-analysis

BACKGROUND Outcome data on simeprevir and sofosbuvir (SMV+SOF) in patients with liver transplantation (LT) with hepatitis C virus genotype 1 (HCV-1) are limited with individual studies having a small sample size and limited SVR12 (sustained virological response) data. Our goal was to perform a meta-analysis to study the outcome of SMV+SOF±ribavirin (RBV) in recipients with LT. METHODS In April 2015, we conducted a literature search for 'simeprevir' in MEDLINE/EMBASE and five major liver meetings. We included studies with SVR12 data in ≥5 post-LT mono-infected HCV-1 patients treated with SMV+SOF±RBV. We used random-effects models to estimate effect sizes, and the Cochrane Q-test (p value <0.10) with I(2) (>50%) to assess study heterogeneity. RESULTS We included nine studies with a total of 325 patients with post-LT. Studies included mostly men (59-81%). Pooled SVR12 was 88.0% (95% CI 83.4% to 91.5%). In two studies, HCV-1a patients with mild fibrosis (n=108) had an SVR12 rate of 95.0% (95% CI 82.4% to 98.7%), which was significantly higher than that of HCV-1a patients with advanced fibrosis (n=49) with an SVR12 rate of 81.7% (95% CI 69.8% to 89.5%), OR 4.2 (95% CI 1.1 to 16.1, p=0.03). The most common pooled side effects were: fatigue 21% (n=48/237), headache 9% (n=23/254), dermatological symptoms 15% (n=38/254), and gastrointestinal symptoms 6% (12/193). CONCLUSIONS SMV+SOF±RBV is safe and effective in recipients with LT with HCV-1 infection.