Interferon‐free therapy for genotype 1 hepatitis C in liver transplant recipients: Real‐world experience from the hepatitis C therapeutic registry and research network

Abstract

Background Recurrent infection with the hepatitis C virus (HCV) after liver transplantation is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition to interferon-free direct-acting antiviral (DAA) regimens. Herein the experience with DAAs in the treatment of post-transplant genotype 1HCV from a consortium of community and academic centers (HCV TARGET) is described. Methods Twenty-one of the 54 centers contributing to the HCV TARGET consortium participated in this study. Enrollment criteria included positive post-transplant HCV RNA prior to treatment, HCV genotype 1, and documentation of use of a simeprevir/sofosbuvir (SMV/SOF) containing DAA regimen. Safety and efficacy were assessed. SVR was defined as undetectable HCV RNA 64 days or later after cessation of treatment. Results A total of 162 patients enrolled in HCV-TARGET started treatment with SMV/SOF with or without ribavirin following liver transplantation. The study population included 151 patients treated with these regimens for whom outcomes and safety data were available. The majority of the 151 patients were treated with sofosbuvir and simeprevir alone (n=119, 78%) or with ribavirin (n=32, 22%), The duration of therapy was 12 weeks for most patients, although 15 patients received 24 weeks of treatment. Of all patients receiving SOF/SIM +/− Ribavirin, 133/151 (88%) achieved SVR12 and 11 relapsed (7%). One patient had virologic breakthrough (n=1) and 6 patients were lost to post treatment follow up. Serious adverse events occurred in 12%; 3 patients (all cirrhotic) died due to aspiration pneumonia, suicide, and multi-organ failure. One experienced liver transplant rejection. Conclusions Interferon-free DAA treatment represents a major improvement over prior interferon-based therapy. Broader application of these and other emerging DAA regimens in the treatment of post-transplant hepatitis C is warranted.

Use of Hepatitis C Positive Organs: Patient Attitudes in Urban Chicago

“…In the DAA therapy era, an improved rate of graft survival has been observed in HCV-positive recipients of HCV-positive organs, with concomitant shorter waitlist times noted in 1 study of kidney transplant patients [9,10]. Moreover, the safety and efficacy of treating HCV with DAA therapy in patients after they receive an HCVpositive organ has been confirmed, with sustained virologic response (SVR) rates similar to those who have not been transplanted [12,13,15]. In a recent study of 10 HCV-negative patients who received HCV antibody and RNA positive kidney grafts and were treated with a single dose of DAA therapy pre-transplant and 12 weeks of DAA therapy post-transplant, the 12 week SVR rate was 100%, and there were no adverse events [18].…”

“…HCV-positive donor organs are now increasingly being transplanted in HCV-positive patients safely and successfully [5,[12][13][14][15]. Additionally, some medical centers are transplanting HCV-positive solid organs in HCVnegative recipients with expectant treatment early in the post-transplant period [16,17].…”

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

“…The recommended antiviral regimens in the post-transplant setting include the following [3,4,[7][8][9][25][26][27][28]:…”

Direct-acting agents for hepatitis C virus before and after liver transplantation

“…In the HCV-TARGET study (30), 151 posttransplant patients infected with HCV genotype 1 were enrolled and received sofosbuvir and simeprevir with (n = 32) and without (n = 119) ribavirin for 12 (n = 136) or 24 weeks (n = 15). The SVR 12 was 88%.…”