Early Post-Liver Transplant Use of Direct-acting Antivirals in Naive and NS5A Inhibitor-Experienced HCV Patients

Margherita Saracco; Francesco Tandoi; Francesca Maletta; Roberto Balagna; Renato Romagnoli; Silvia Martini


J Viral Hepat. 2023;30(3):201-208. 

In This Article

Abstract and Introduction


Direct-acting antiviral drugs (DAA) are safe and effective in the HCV population. However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma or relapse to NS5A inhibitors, response rates are lower and DAA therapy must be postponed until after liver transplant in an era of organ shortage and suboptimal donors. We aimed to assess the prevalence of patients still HCV infected at time of transplantation over the last 3 years in our Center and describe the safety and efficacy of DAA therapy started as soon as possible after surgery. We enrolled all HCV viraemic patients transplanted in our Centre from January 2019 to March 2022. The follow-up was closed in July 2022. Among 490 liver transplants, 49 (10%) patients were still HCV viraemic at operation, 43 naive to DAA and 6 were NS5A-experienced. Median donor age was 64 years; donor risk index was 1.8. In naive patients, sofosbuvir/velpatasvir was started after a median time of 1 day from surgery, while in NS5A-experienced sofosbuvir/velpatasvir/voxilaprevir after 14.5 days (p = .001). Response rate was 98%. 1 NS5A-experienced patient experienced acute cholestatic hepatitis which promptly reverted after permanent DAA discontinuation. Hence, very early post-liver transplant HCV eradication was safe and effective thanks to a close teamwork which involved anaesthesiologists, transplant surgeons and hepatologists.


Since the advent of direct-acting antivirals (DAAs), the Scientific Community assisted to a rapid decline of liver transplant (LT) indication for hepatitis C virus (HCV) cirrhosis.[1,2] It is estimated, however, that 58 million people suffer from chronic HCV infection across the world, with about 1.5 million new infections occurring per year,[3] and unfortunately, the World Health Organization's 2030 elimination target has been slowed down due to the coronavirus disease 2019 pandemic.[4,5]

A huge amount of data about the efficacy and safety of DAAs in HCV population are now available, with an overall sustained viral response rate after 12 weeks from the end of therapy (SVR12) above 95%.[6–10] However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma (HCC) SVR12 rates are lower, around 80–90%.[11–13] In addition, the NS3/4A protease inhibitor-containing regimens such as sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (indicated by international guidelines[14,15] for NS5A inhibitors experienced patients) are not recommended in patients with moderate to severe hepatic impairment (Child-Pugh B or C) and in patients with previous episodes of decompensation due to the risk of hepatic decompensation/failure.[14–16] Consequently, current management of HCV viraemic patients with decompensated cirrhosis and/or active HCC and/or experienced to NS5A inhibitors remains cumbersome and antiviral therapy of LT candidates with those features must be postponed after LT. Yet the optimal timing to start post-LT DAA therapy is still matter of debate. The American[14] and European[15] Associations for the Study of Liver disease suggest to commence DAA within the first 3–6 months post-transplant. Levitsky et al.[17] published a phase II trial in which 16 patients were treated with sofosbuvir/ledipasvir (SOF/LED) for 29 days starting the day before LT; the SVR12 rate was 88%. Reau et al.[18] managed 80 patients with glecapresvir/pibrentasvir after a median time of 53.8 months (range 4.2–213.7 months) from surgery and the SVR12 rate was 99%. Agarwal et al.[19] treated 79 post-LT patients with SOF/VEL for 12 weeks, after a median time of 7.5 years (range 0.3–24) from surgery and they achieved a SVR12 of 96%. More recently, the United States HCC LT Consortium[20] enrolled 725 patients from 2015 to 2019, reporting that the optimal timing of DAA therapy appeared to be 0–3 months after LT. Finally, Higley et al.[21] published 6 patients who failed NS5A inhibitors before LT and underwent successful SOF/VEL/VOX 4 months after LT. However, none of these papers reported data about graft quality and donor age.

Noteworthy, in Europe, and especially in Italy,[22,23] the age of liver donors has been steadily increasing in the last years to expand the donor pool and to reduce the organ shortage. In this context of suboptimal grafts, we speculate that very early post-LT HCV eradication both in naive and NS5A-experienced recipients could be a safe and the most effective option to pursue. Indeed, an untreated HCV recurrent infection in an elderly liver graft could compromise its functional recovery from the initial post-LT phase.[24]

Therefore, we collected the data regarding LTs performed in our Centre from 1 January 2019 to 31 March 2022. In this real-life cohort, we assessed the prevalence of patients who were HCV viraemic at LT (naive or relapser to NS5A) and we describe herein the results of an aggressive antiviral approach in which DAA therapy was started as soon as possible after LT.