Filling the gap between clinical trials and real life in the treatment of severe HCV recurrence after liver transplantation

Abstract

In this issue of Transplant International, Herzer et al.[1] report the results obtained in a real-world European cohort of 87 patients with severe recurrent hepatitis C (HCV) after liver transplantation (LT), who were treated with a compassionate use of daclatasvir (DCV) plus registered sofosbuvir (SOF), with or without ribavirin (RBV). The vast majority of patients were HCV genotype 1, although the sample included a few with genotypes 3 and 4. It is noteworthy that 37/87 patients (42.5%) had cirrhosis (and 16/37 patients [43%] had Child-Pugh B/C decompensated cirrhosis). Forty of the 87 patients (46%) had moderate or severe renal impairment (CrCl <60 ml/min/1.73 m 2 ). Low platelet counts (<100 9 10 9 /l) and low albumin levels (<35 g/l) were identified in 27 (31%) and 13 (15%) patients, respectively. Five of the 37 cirrhotic patients (13.5%) had fibrosing cholestatic hepatitis (FCH). Excluding the five nonvirological failures (four patients with decompensated cirrhosis who died-one during and three after the treatment-of causes related to their advanced liver disease, and one patient lost to follow-up after discontinuing the treatment due to acute kidney injury with lactic acidosis), the rate of sustained virological response 12 weeks after the end of the therapy (SVR12) was 100% (80/80). During the treatment, 16/87 patients (18.4%) experienced severe adverse events (AEs) and a very small proportion of them (4/87, 4.6%) discontinued the therapy. No significant drug-drug interactions (DDIs) or episodes of acute rejection were reported.We all agree that the "new era" of antiviral therapy associated with the recent approval of highly effective and well-tolerated regimens of direct-acting antiviral agents (DAAs) has revolutionized the approach to the burden of HCV after LT [2], and several prospective trials have already been published on this topic [3][4][5][6][7]. These trials were relatively small, however, and-given concerns about the impact of immunosuppression on response rates-patients were treated with RBV-containing regimens, most of them for as long as 24 weeks. Establishing the safety of DAAs in patients with advanced liver disease and/or renal insufficiency, and the related DDIs with immunosuppressants is still a challenge, although it is clearly much less so than it was in the "stone age" of interferon (IFN)-based antiviral therapy.ª 2017 Steunstichting ESOT 239

Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat patients with recurrent hepatitis C virus infection after liver transplantation: a real-world cohort

“…However, there is only a limited database for its use in LT recipients, and especially a gap prevails in clinical real-world data 15–18…”