Safety and Efficacy of Simeprevir/Sofosbuvir in Hepatitis C–Infected Patients With Compensated and Decompensated Cirrhosis

Abstract

Background/Aims Risks and benefits of simeprevir plus sofosbuvir in patients with advanced cirrhosis are unknown. We assessed the safety and sustained virologic responses (SVR) of simeprevir plus sofosbuvir with and without ribavirin in patients with Child-Pugh (CP)-B/C vs. CP-A cirrhosis and compared to matched untreated controls. Methods Multicenter cohort of adults with HCV genotype 1 and cirrhosis treated with simeprevir plus sofosbuvir with/without ribavirin for 12 weeks. Controls were matched on treatment center, age, CP class and model for end-stage liver disease (MELD) score. Results Of 160 patients treated with simeprevir plus sofosbuvir with/without ribavirin, 35% had CP-B/C and 64% had CP-A, with median baseline MELD 9 (IQR 8–11). SVR12 was achieved by 73% of CP-B/C vs. 91% of CP-A (p<0.01). CP-B/C vs. CP-A had more early treatment discontinuations (11% vs. 1%), adverse events requiring hospitalization (22% vs. 2%), infections requiring antibiotics (20% vs. 1%) and hepatic decompensating events (20% vs. 3%) (all p<0.01). There were 2 deaths: 1 CP-B/C (liver-related) and 1 CP-A (not liver-related). In multivariate analysis, CP-B/C independently predicted lack of SVR12 (OR 0.27, 95% CI 0.08–0.92). In comparing simeprevir plus sofosbuvir treated patients vs. matched untreated controls, adverse events requiring hospitalization (9% vs. 13%, p=0.55), infections (8% vs. 6%, p=0.47) and events of decompensation (9% vs. 10%, p=0.78) occurred at similar frequency. Conclusions Simeprevir plus sofosbuvir with/without ribavirin has lower efficacy and higher rates of adverse events in patients with CP-B/C cirrhosis compared to CP-A. The frequency of adverse safety outcomes were similar to matched untreated controls, suggesting safety events reflect the natural history of cirrhosis and are not related to treatment.

Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation?

“…[33][34][35][36] Many of these trials included patients awaiting LT, 31,37 and those with decompensated cirrhosis of liver. 31,38,39 There are several controlled trials with interesting acronyms such as ALLY-1, SOLAR-1, SOLAR-2, SATURN and CORAL-1, which have shown that it is now feasible to treat patients with decompensated cirrhosis (Table 1). In addition, there have been several real world data studies which have given similar conclusions.…”

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“…Ten patients died, mainly from complications related to hepatic decompensation. 27 The results of another study by Saxena and associates 28 evaluated the use sofosbuvir and simeprevir with or without ribavirin for treatment of patients with compensated and decompensated cirrhosis from HCV genotype 1. The study enrolled 160 patients, with 35% scored as Child-Pugh class B/C.…”

“…Furthermore, SVR12 was achieved by 74% of patients with early severe recurrent hepatitis who did not undergo retransplant (74% with sofosbuvir and ribavirin and 71% with sofosbuvir and pegylated interferon with ribavirin). 28 Several reports have demonstrated the effectiveness of sofosbuvir and simeprevir in the posttransplant setting. The use of simeprevir is contraindicated in recipients who are receiving cyclosporine as part of the immunosuppressant regimen.…”

Hepatitis C Virus and Liver Transplantation

“…12 The PRO/PROD regimen is contraindicated in patients of 87%. 20 The group that received sofosbuvir/velpatasvir plus ribavirin for 12 weeks achieved the highest SVR12 rate (94%) compared to the groups without ribavirin for 12 weeks (83%) or 24 weeks (86%).…”