Treatment of hepatitis C virus recurrence after transplantation with sofosbuvir/ledipasvir: The role of ribavirin.

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon-based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12-week SOF/LDV treatment in the post-transplant setting, is still unanswered. At our institution, 100 liver transplant patients with HCV recurrence underwent interferon-free SOF-based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty-nine HCV genotype 1 or 4 patients with histologically proven stage 0-2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3-4) either received SOF/LDV plus weight-adjusted RBV or prolonged treatment for 24 weeks. End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P<.001. One of the predominant and most relevant AEs was the development of anemia in 43.1% of 10 patients receiving RBV, which was a significant result (P<.001). RBV co-medication had to be reduced in 11 (55%) patients and then stopped in 8 (40%) patients because of AEs. No significant difference was observed among the groups regarding kidney function. The SOF/LDV combination is a reliable therapy of recurrent HCV infection after LT. It is easy to administer and to achieve SVR in immunocompromised patients without interactions with immunosuppressive medications. Considering the high rate of AEs, frequent discontinuation of RBV treatment, and the 100% SVR, the use of RBV as co-medication in a 12-week SOF/LDV regimen does not seem to be justified after LT.

Globke B ，Raschzok N ，Teegen EM ，Pratschke J ，Schott E ，Eurich D ... -  《-》

Efficacy and safety of sofosbuvir/ledipasvir for the treatment of patients with hepatitis C virus re-infection after liver transplantation.

Hepatitis C virus (HCV) infection is associated with a particularly poor outcome after liver transplantation. In December 2014, sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) was approved for HCV genotype 1 and 4 in Europe. In orthotopic liver transplantation (OLT) recipients, the interferon-free treatment of HCV re-infection with novel direct-acting antivirals has been demonstrated to be safe and effective in clinical trials, but real-world data are missing. The aim of this study was to investigate the safety and efficacy of SOF/LDV FDC in OLT recipients in the real-life setting. All consecutive OLT patients started on SOF/LDV FDC for 12 or 24 weeks at the University Medical Center Hamburg-Eppendorf and Medical School Hannover between October 2014 and August 2015 were retrospectively analyzed (n = 30). The primary efficacy endpoint was sustained virological response (SVR), i.e., absence of viremia 12 weeks after end of treatment (SVR 12). Liver function tests, creatinine, blood count, and HCV RNA (by polymerase chain reaction assay) were determined at each visit. SVR was achieved in 29/30 patients (96.67%) treated with SOF/LDV ± ribavirin (RBV) for 12 (n = 4) or 24 weeks (n = 25). Twenty-five patients (86.2%) received RBV. However, in 15 of the 25 patients, RBV administration had to be discontinued because of severe anemia (57.7%). One RBV-treated patient died of a myocardial infarction during antiviral therapy; this event was most likely not directly related to SOF/LDV. Aside from RBV-associated anemia, no severe side effects of the antiviral regimen were observed. Antiviral treatment with SOF/LDV is highly effective, safe, and well tolerated in OLT recipients. The addition of RBV often results in severe anemia, requiring dose reduction or discontinuation.

Ciesek S ，Proske V ，Otto B ，Pischke S ，Costa R ，Lüthgehetmann M ，Polywka S ，Klempnauer J ，Nashan B ，Manns MP ，von Hahn T ，Lohse AW ，Wedemeyer H ，Mix H ，Sterneck M ... -  《-》

Multicenter Experience using Ledipasvir/Sofosbuvir ± RBV to Treat HCV GT 1 Relapsers after Simeprevir and Sofosbuvir Treatment.

Aqel B ，Leise M ，Vargas HE ，Watt KD ，Keaveny AP ，Zhang N ，Zhang N ，Pungpapong S ... -  《Annals of Hepatology》

Efficacy and Safety of Ledipasvir/Sofosbuvir with and without Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: a meta-analysis.

The addition of ribavirin (RBV) to the combination treatment of Ledipasvir (LDV) and Sofosbuvir (SOF) remains controversial in the treatment of hepatitis C virus (HCV) infection. We performed a meta-analysis to assess the efficacy and safety of the LDV-SOF with and without RBV in treating HCV genotype 1 patients. The electronical databases of PubMed Medline, EMBASE database, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov website with registered trials were searched. Eligible studies were randomized controlled trials (RCTs) and prospective cohort studies that assessed the efficacy and safety of LDV-SOF with or without RBV in patients with HCV genotype 1 (GT 1). Two reviewers independently screened studies, extracted data and assessed methodology quality. Review Manager 5.3 software was used to analyze the data. Seven studies involving 2,626 patients with HCV GT 1 - some of whom had cirrhosis - were included in this meta-analysis. The addition of RBV to LDV- SOF regimen neither significantly improved sustained viral response at 12 weeks (SVR12) after the last dose of treatment (RR=1.00, 95%CI 0.99-1.01, p=0.99) nor decreased virologic breakthrough (RR=1.01, 95%CI 0.14-7.19, p=0.99) and relapse (RR=1.36, 95% CI 0.81-2.29, p=0.24). There was no significant difference in the incidence of discontinuation (RR=0.61, 95%CI 0.25-1.53, p=0.30) between LDV- SOF therapy and LDV- SOF plus RBV. LDV- SOF plus RBV therapy had significantly higher rate of the overall adverse events (RR=0.88, 95%CI=0.84- 0.92, p<0.00001). LDV - SOF therapy had higher incidence of serious adverse events (RR=1.60, 95%CI=1.00-2.56, p=0.05) than LDV-SOF plus RBV. This meta-analysis suggests that LDV-SOF based therapy is a safe and effective treatment for patients with GT 1 HCV. The addition of RBV to LDV-SOF may increase toxicity without achieving improved efficacy. However, due to the relatively small sample sizes and moderate risk of bias of included studies, large-scale and high-quality clinical research is still needed to confirm the results.

Tao T ，Jiang X ，Chen Y ，Song Y ... -  《-》

Sofosbuvir/Ledipasvir Without Ribavirin Achieved High Sustained Virologic Response for Hepatitis C Recurrence After Liver Transplantation: Two-Center Experience.

Elfeki MA ，Abou Mrad R ，Modaresi Esfeh J ，Zein NN ，Eghtesad B ，Zervos X ，Hanouneh IA ，O'Shea R ，Carey WD ，Alkhouri N ... -  《-》