Improved Graft Survival After Liver Transplantation for Recipients With Hepatitis C Virus in the Direct‐Acting Antiviral Era

Abstract

Highly effective direct‐acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer‐term outcomes in HCV‐positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single‐organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018. Graft loss was compared among HCV‐positive liver transplant recipients who received either an HCV‐negative or HCV‐positive donor (donor [D]–/recipient [R]+; D+/R+) and HCV‐negative liver transplant recipients who received a HCV‐negative donor (D–/R–). The groups were further divided between the pre‐DAA and DAA eras. There were 52,526 patients included: 31,193 were D–/R– patients; 18,746 were D–/R+ patients; and 2587 were D+/R+ patients. The number of D–/R+ transplants decreased from 2010 in 2008 to 1334 in 2017, with this decline particularly noticeable since 2015. D–/R+ patients in the DAA era (n = 7107) were older, had higher rates of hepatocellular carcinoma, and lower Model for End‐Stage Liver Disease scores than those in the pre‐DAA era. Graft survival improved for all recipients in the DAA era but improved most dramatically in HCV‐positive recipients: D–/R+ 1‐year survival was 92.4% versus 88.7% and 3‐year survival was 83.7% versus 77.7% (DAA versus pre‐DAA era, respectively) compared with D–/R– 1‐year survival of 92.7% versus 91.0% and 3‐year survival of 85.7% versus 84.0% (DAA versus pre‐DAA era, respectively). The magnitude of improvement in 3‐year graft survival was almost 4‐fold greater for D–/R+ patients. The 3‐year survival for D+/R+ patients was similar to HCV‐negative patients. In conclusion, the number of liver transplants for HCV has decreased by more than one‐third over the past decade. Graft survival among HCV‐positive recipients has increased disproportionately in the DAA era with HCV‐positive recipients now achieving similar outcomes to non‐HCV recipients.

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

“…Even among these patients, the persistence of HCV infection post‐transplantation was associated with poor outcomes and led to worse post‐transplant survival . However, the advent of highly effective direct‐acting antiviral therapy (DAAs) has led to post‐transplantation HCV cure rates exceeding 95%, and with it, a negation of the ill effects of HCV previously seen in both LT and KT recipients . A number of clinical trials, along with data from the HCV‐TARGET cohort, have demonstrated the efficacy and safety of the use of these agents in the post‐transplant setting .…”

“…Newer agents, including glecaprevir/pibrentasvir (GLE/PIB), have similarly been shown to be safe and efficacious . Indeed, recently published data derived from the Scientific Registry of Transplant Recipients (SRTR) suggest equivalent 1‐ and 3‐year survival among HCV‐infected patients undergoing LT …”

The Reliability of Fibro-test in Staging Orthotopic Liver Transplant Recipients with Recurrent Hepatitis C

“…[1][2][3] There is no denying that the use of DAAs in liver recipients with RHC or even kidney recipients with de novo HCV infection has largely mitigated this problem, enabling timely, safe and cost-effective viral eradication. 4,5,15 However, data on the utilization of DAAs post-transplant are limited when compared to the abundance of large and small, prospective and retrospective studies in immunocompetent patients. The introduction of all-oral, interferon-free DAAs into routine clinical practice is relatively recent (sofosbuvir/ ledipasvir attained Federal Drug Administration approval in October of 2014, with others following suit), and as such there is paucity of robust data on the SVR rates in DAA-and more specifically the NS5A-experienced OLT recipients with RHC.…”

“…Allograft re-infection by the hepatitis C virus (HCV) in treatment-naïve or unsuccessfully treated orthotopic liver transplant (OLT) recipients is swift and universal and used to be associated with an accelerated rate of fibrosis progression. [1][2][3] The advent of direct-acting antivirals (DAAs) dramatically changed the landscape of HCV treatment, with safe and effective regimens that have high cure rates leading to significantly improved outcomes in the post-OLT setting 4,5 Still, treatment of recurrent hepatitis C (RHC) in liver transplant recipients may pose a challenge. 6 As such, there remains the necessity to periodically restage the relatively few patients who either fail or are unable to tolerate DAA treatment.…”

Recent advances in liver transplantation for cancer: The future of transplant oncology

“…66,67 Cotter et al demonstrated that, in the DAA era, there has been an increase in the utilisation of HCV-viraemic donor livers, including into HCVnegative recipients, with good graft outcomes. 68 The use of DAAs has changed the landscape of HCV treatment and, annually, less patients with endstage liver disease due to HCV are listed for LT. [68][69][70][71][72][73][74] Living donor liver transplantation The most important intervention to increase the donor pool is living donor liver transplantation (LDLT). Initial results on LDLT for HCC indicated an increased risk of recurrence.…”