Transplanting HCV-positive livers into HCV-negative patients with preemptive antiviral treatment: A modeling study

ABSTRACT

Under current guidelines hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse post-transplant outcomes associated with allograft HCV infection. However, HCV can now be cured post liver transplant (LT) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the liver transplant (LT) waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate if and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: 1) willing to accept any (HCV-negative or HCV-positive) liver versus 2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when MELD was ≥ 20, and the benefit was highest at MELD 28 (0.172 additional life years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, i.e. Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust.

Conclusions: Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. This article is protected by copyright. All rights reserved.

http://ift.tt/2AHgjdb