Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 after liver transplant

Abstract

Treatment with an all-oral interferon-free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non-liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3-F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV-based regimens) received treatment and were followed for a median of 30 weeks (range 12-53 weeks). The median time from LT to treatment was 32 months (range 2-317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%-96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3-F4 (71%) compared to those with F0-F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug-induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention. Conclusion: An all-oral interferon-free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection. (HEPATOLOGY 2015;61:1880-1886 H epatitis C viral (HCV) infection is the leading indication for liver transplant (LT) worldwide. Recurrence of HCV is universal among recipients with viremia at the time of transplant and occurs immediately after LT. 1,2 Although the clinical course of HCV recurrence is variable, severe histological recurrence is the most common cause of graft loss and death, which accounts for approximately 60% of graft losses and nearly 50% of deaths by 10 years after LT. 3,4 Liver allograft and recipient survival can be substantially improved with successful eradication of HCV. 5,6 Treatment with pegylated interferon (Peg-IFN) and ribavirin (RBV) was not effective and poorly tolerated in the post-LT setting, with reported sustained virologic response (SVR) rates ranging 24%-45% for patients with HCV genotype 1. 7,8 The combination of direct-acting antiviral agents, in the form of a firstgeneration protease inhibitor (PI), telaprevir or boceprevir, with Peg-IFN and RBV improved SVR rates to

Paritaprevir-Ritonavir, Ombitasvir and Dasabuvir plus Ribavirin to Treat Hepatitis C Genotype 1 Infection after Liver Transplantation: A Single-Center Experience

“…Several studies have been published recently on sofosbuvir-based regimens combined with other DAAs in transplant recipients with genotype 1 infection. SVR rates at 12 weeks post-treatment were consistently higher than 85% (9,10).…”

“…These results were surpassed by other more effective combinations such as sofosbuvir and simprevir [9] or sofusbuvir and daclatasvir [10].…”

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“…32 The authors demonstrated an overall SVR of 90% with minimal adverse effects. Of the 123 patients, 98 received sofosbuvir and simeprevir and 25 had the addition of ribavirin.…”

“…32 Sixty-one patients with HCV genotype 1 were treated with sofosbuvir and simeprevir for 12 weeks; 3 of these patients also received ribavirin. 27 12 wk 96%-98% (NC and Child-Pugh class A) Need for ribavirin 85%-88% (Child-Pugh class B) 60%-75% (Child-Pugh class C) 3-D + ribavirin 34 24 34 Dosage modifications of calcineurin inhibitors were based on blood levels.…”

Multidisciplinary Approach to treat Liver Transplant Recipients with Hepatitis C using Sofosbuvir based Therapy

“…Authors of this trial demonstrated high efficacy with an overall SVR-12 rate of 97%, which is comparable with our experience in patients with milder recurrent HCV infection. A recent study in which 12 patients with recurrent HCV after liver transplantation received sofosbuvir with and without RBV concluded that optimal outcomes require initiation of treatment before decompensation [30]. Based on that we recommend initiating AVT in mild disease to get maximum outcome in LT recipients.…”