Could DAAs Improve Safety of HCV-Positive Liver Transplantation?

The transplantation of hepatitis C virus (HCV)-positive livers into HCV-negative patients is not recommended under current guidelines due to adverse post-transplant outcomes associated with allograft HCV infection. However, in the age of direct-acting antiviral (DAA) therapy, this may become a viable option for patients on the liver transplant (LT) waiting list.¹

Because of DAA therapy, HCV can often be cured following LT with more than 90% success. As a result, HCV-negative patients who are willing to accept an HCV-positive liver and receive preemptive DAA therapy may experience greater survival rates than those who will only accept an HCV-negative liver, according to a new study.

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For their study, Jagpreet Chhatwal, PhD, of Harvard Medical School in Boston, Massachusetts, and colleagues constructed a Markov-based mathematical model that simulated a virtual trial of patients without HCV who were on the waiting list to undergo LT.

The model compared long-term outcomes between patients willing to accept either an HCV-positive or HCV–negative liver vs those who were only willing to accept an HCV-negative liver. Data were obtained from published studies and the United Network for Organ Sharing (UNOS).

Patients who opted to receive an HCV-positive liver were treated with DAA therapy for 12 weeks prior to LT. Compared with patients receiving a HCV-negative liver, those receiving an HCV-positive liver had a higher risk of graft failure.

Ultimately, the results of the study showed that accepting any liver regardless of HCV status was associated with a higher life expectancy compared with accepting only an HCV-negative liver when Model for End‐Stage Liver Disease (MELD) scores were at least 20. Patients with a MELD score of 28 demonstrated the greatest benefit (0.172 additional life‐years).

The researchers noted that patients in UNOS regions with higher rates of HCV-positive organ donations tended to experience a greater clinical benefit.

Model findings were deemed robust based on sensitivity analysis findings.

“Transplanting HCV‐positive livers into HCV‐negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list,” the researchers concluded. “Our analysis can help inform clinical trials and minimize patient harm.”

—Christina Vogt

Reference:

1. Chhatwal J, Samur S, Bethea ED, et al. Transplanting hepatitis C virus–positive livers into hepatitis C virus–negative patients with preemptive antiviral treatment: A modeling study. Hepatology. 2018;67(6):2085-2095. https://doi.org/10.1002/hep.29723