Jagpreet Chhatwal, PhD, and Emily Bethea, MD, on HCV-Positive Liver Transplantation With Preemptive DAAs
Alcoholic liver disease, liver cancers combined with cirrhosis, nonalcoholic steatohepatitis, and cirrhosis caused by chronic hepatitis C virus (HCV) are among the top reasons for needing a liver transplant.1
However, despite the need, there is a perpetual shortage of viable organs for transplant, and the wait list is often lengthy.
Transplanting HCV-positive livers into HCV-negative individuals is not recommended under current guidelines due to various safety concerns, but in the era of direct-acting antiviral (DAA) therapy, this could change.2
Findings from a recent study indicate that treating HCV-negative individuals preemptively with DAAs prior to receiving an HCV-positive liver may not only be a safe option, but that this practice could also reduce the wait time for viable livers and thus improve survival among patients on the wait list.2
Consultant360 discussed these findings and their implications further with study authors Jagpreet Chhatwal, PhD, senior scientist at the Institute for Technology Assessment at Massachusetts General Hospital and assistant professor at Harvard Medical School in Boston; and Emily Bethea, MD, advanced transplant hepatology fellow at the Liver Center and the Gastrointestinal Division at Massachusetts General Hospital.
Consultant360: How did your study come about? What is the importance behind the transplantation of HCV-positive livers into HCV-negative patients being a potentially viable option in the DAA era?
Jagpreet Chhatwal and Emily Bethea: Under current practice, HCV-infected livers can potentially be discarded if no HCV-positive patients are available to accept these organs. Because there remains a shortage of viable organs for transplant, it is important to maximize the use of available organs to their full potential. The recent availability of highly efficacious and well-tolerated DAA drugs provides the unprecedented opportunity to successfully treat HCV infection in the post-transplant setting. Therefore, HCV-infected organs can be offered to HCV-negative patients who can be treated with DAAs post-transplant. By becoming open to accepting an HCV-infected liver, HCV-negative patients can increase their likelihood of receiving a liver transplant.
Another reason that makes utilization of HCV-positive livers even more important is that the supply of HCV-infected livers has increased in the last few years because of the persistent opioid epidemic; but on the other hand, the number of HCV-positive patients on the transplant waitlist has decreased. All of these factors have led to increased interest in exploring the possibility of utilizing HCV-positive livers in HCV-negative patients on the transplant waiting list.
Since a randomized clinical trial analyzing this question would need to be large and conducted over several years, the Massachusetts General Hospital team conducted a virtual trial by simulating the life courses of HCV-negative patients on the waiting list, and comparing the risks and benefits of transplanting HCV-positive livers into HCV-negative patients.
C360: How safe is it for HCV-negative patients to receive an HCV-positive liver with preemptive DAA therapy? Could it be safe for all patients on the transplant wait list, or would it be contraindicated in some cases?
Authors: This is an excellent question. Even though DAAs are highly effective – offering 95% to 100% cure rates—it is possible that HCV-negative patients may become infected and not get cured even with multiple treatment attempts. In addition, some livers with HCV may have scar—also called fibrosis—which can increase some post-transplant related risks, but they can still be viable organs for transplant. Other livers may have no fibrosis or scar, making them ideal organs for transplant if HCV can be successfully treated.
While there are risks associated with receipt of an HCV-infected organ, many patients have limited options and face a high waitlist mortality. In many cases, it comes down to individual patient characteristics and informed discussions on the risks and benefits between recipients and providers. In the majority of these cases, the risks associated with not receiving a transplant are greater than the potential risk of not being able to successfully treat HCV in the post-transplant setting.
C360: What implications could the findings from your study have for existing guidelines in the future?
Authors: Our analysis revealed that the benefits of accepting an HCV-positive liver outweigh the risks in the majority of patients on the transplant waiting list. The magnitude of the benefits depended on the severity of a patient’s liver disease, which is measured by the Model for End‐Stage Liver Disease (MELD) score. Determined by a number of laboratory values, the MELD score ranges from 6 to 40, with a higher score indicating more severe illness.
Demonstrating that this approach is clinically beneficial can start conversation on changing guidelines to more routinely consider the use of HCV donor-positive to recipient-negative transplant.
C360: What are the next steps in your research?
Authors: The reimbursement for DAA treatment in this setting remains a barrier. Insurers often deny coverage of treatment, thus placing the burden of the cost of DAAs on individual patients. The next step is to evaluate the cost-effectiveness of transplanting HCV-infected livers into HCV-negative recipients with preemptive DAA treatment.
C360: What would you say to clinicians who may be concerned about the ethical implications behind transplantation of HCV-positive livers into HCV-negative individuals?
Authors: For years, we have used organs with plans to treat donor derived infection post-transplant. For example, in hepatitis B virus (HBV) core antibody positive donor livers with dormant HBV, we commit recipient patients to lifelong antiviral therapy to suppress HBV reactivation without achieving a cure. This is not considered ‘unethical’ and the benefit of life-saving transplant is often believed to outweigh potential associated infectious risks. HCV falls into a similar bucket, but here we are able to potentially achieve cure, and are committing patients to a limited 3 total months of DAA treatment post-transplant.
Every patient has extensive discussions with their care providers during the transplant listing process, and part of these discussions include decisions on accepting a ‘high-risk’ donor organ, such as one that tests positive for HCV. There are always complicated ethical questions in transplant, which highlights the need for more work in this area, with plans to develop standardized informed consent and education within the transplant community.
For our coverage of Dr Chhatwal and Dr Bethea’s study, click here.
—Christina Vogt
References:
1. Definition & facts of liver transplant. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant/definition-facts Accessed on July 30, 2018.
2. 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