Abstract

ObjectivesDirect antiviral agents (DAA) has dramatically improved the therapy outcome of hepatitis C-virus (HCV) infection, both on the waiting-list and post liver transplantation (LT). DAA are generally well-tolerated in patients with mild to moderate liver and kidney failure, but some DAAs are contraindicated in patients with severe dysfunction of these organs. Today there are few studies of peri-LT DAA use and treatment is commonly discontinued at the time of LT. We report here our experience of DAA therapy given continuously in the perioperative LT period in a real-life setting in Sweden.MaterialIn total 10 patients with HCV-cirrhosis, with or without hepatocellular carcinoma, and a median age of 60.5 years (range, 52–65) were treated with DAAs on the waiting list for LT, and continued in the early postoperative period without any interruption, on the basis of not having reached a full treatment course at the time of LT. Sofosbuvir and a NS5A inhibitor with or without ribavirin, or sofosbuvir and ribavirin only, were given. The distribution of genotypes was genotype 1 and 3, in 4 and 6 patients, respectively. Six of the 10 patients had previously been treated with IFN-based therapy.ResultsThere were no adverse events leading to premature DAA discontinuation. All recipients achieved a sustained viral response 12 weeks after end-of-treatment (SVR12). At the time of LT the median MELD-score was 16.5 (range 7–21), CTP-score 9.0 (range 5–10), creatinine 82.5 μmol/L (range 56–135, reference 60–105), bilirubin 33 μmol/L (range 16–79, reference 5–25) and PK-INR 1.5 (range 1.1–1.8). The median duration of DAA therapy was 60 days (range 18–132) pre-LT, 54 days post-LT (range 8–111 days) and in total 15.5 weeks (range 12–30 weeks).ConclusionInterferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative LT period is safe, well-tolerated and yields high SVR rates.

Highlights

  • Chronic hepatitis C virus (HCV) infection affects an estimated 71 million people in the world with fatal consequences in approximately 400,000 persons per year [1]

  • There were no adverse events leading to premature Direct antiviral agents (DAA) discontinuation

  • Interferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative liver transplantation (LT) period is safe, well-tolerated and yields high sustained viral response (SVR) rates

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Summary

Introduction

Chronic hepatitis C virus (HCV) infection affects an estimated 71 million people in the world with fatal consequences in approximately 400,000 persons per year [1]. About 20% of the chronically infected patients develop cirrhosis or liver cancer, necessitating liver transplantation (LT) within 20 years postinfection. HCV-infection in LT recipients has an accelerated progress and 20–30% will develop cirrhosis within 5-years post-LT if not treated [2, 3, 4]. Tolerance of the previous standard-of-care (SOC) treatment, pegylated-interferon (pegIFN) and ribavirin (RBV), in cirrhotic patients as well as LT recipients was suboptimal due to severe side-effects such as infections and increased risk of rejection, leading to frequent cessation of therapy [7]. Peg-IFN and RBV combination therapy in LT patients yielded SVR rates as low as 20–45%, with only 15–30% of genotype 1 infected recipients achieving SVR [3, 8]. In the new era of IFN-free therapy with DAA, outcome has improved dramatically both on the waiting list for LT and post-LT due to fewer side-effects [9,10,11,12]

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