Transplanting livers infected with hepatitis C virus (HCV) into uninfected patients, who are given direct-acting antiviral (DAA) drugs, could improve patient survival and shorten the time spent on the liver transplant waiting list, according to results from a recent study published in Hepatology.
“The availability of donor livers continues to be the limiting factor in increasing the number of liver transplant surgeries,” said the study’s lead author Jagpreet Chhatwal, PhD, a decision scientist at Massachusetts General Hospital’s Institute for Technology Assessment, Boston, MA.
“Our study shows that transplanting HCV-positive livers into HCV-negative patients and treating with new antivirals can reduce waiting time to transplant and improve overall life expectancy,” added Dr. Chhatwal, who is also an assistant professor at Harvard Medical School.
Risks vs benefits
Currently, HCV-positive organs are often discarded despite a rising need for organ transplants—and an increased number of HCV-positive livers due to the growing opioid epidemic. “Persons who inject drugs are now the fastest-growing category of donor,” Dr. Chhatwal and colleagues wrote.
At the same time, HCV-positive livers have been successfully transplanted into HCV-positive recipients without an increase in graft loss or mortality. Also, newly developed DAAs can treat HCV with cure rates greater than 90% after liver transplant. These advances indicate that HCV-negative patients could benefit from accepting HCV-positive donor organs along with DAA treatment, the investigators reasoned.
“Particularly, accepting HCV-positive organs could reduce patients’ time to transplant and waitlist-associated mortality,” they noted. “[H]owever, it could also increase potential post-liver transplant complications associated with HCV allograft infection.”
But where should the line be drawn between the possible benefits and potential risks of transplanting HCV-positive livers? Although a randomized controlled trial would shed light on the trade-offs, “such a trial will be prohibitively large, time consuming, or even unethical in some cases,” Dr. Chhatwal and colleagues wrote.
Instead, the investigators used a mathematical model to simulate a virtual trial of HCV-negative patients on the liver transplant waiting list. The trial compared long-term outcomes between patients willing to accept any (HCV-negative or HCV-positive) liver versus those willing to accept only HCV-negative livers.
The researchers used a prior study to estimate the weekly probability of receiving a liver transplant based on each patient’s “model for end-stage liver disease” (MELD) score, in which a higher score indicates more severe illness.
A change in practice?
Upon analysis, their results showed that the benefits of accepting an HCV-positive liver outweighed the risks for most patients on the waiting list.
“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,” at which point patients gained an additional 0.172 life years, Dr. Chhatwal and colleagues wrote.
They added, “Given that a large number of patients awaiting liver transplant in the US have MELD scores greater than 20, a change in practice towards a willingness to accept HCV-positive livers would benefit the majority of waitlist population.”
The benefit was also greatest for patients living in regions of the United States with higher HCV-positive donor organ rates, which are the areas most affected by the opioid crisis.
But the researchers noted that, “In patients with MELD below 20, the risk of HCV allograft infection was not offset by the benefits of receiving liver transplant sooner; instead of accepting an HCV-positive liver, they would be better off waiting for an HCV-negative liver until their MELD score increased to at least 20.”
The investigators anticipate that providers will add “HCV-positive livers” to their discussion with patients about “extended donor criteria” during the transplant listing process.
However, “More clinical studies evaluating the use of HCV-positive donor livers and the efficacy and optimal treatment duration for antiviral drugs will be needed before this approach can be widely applied,” said study coauthor Raymond Chung, MD, director of hepatology and medical director of the Liver Transplant Program at Massachusetts General Hospital.