Use of HCV-infected Organs in Solid Organ Transplantation

An Ethical Challenge But Plausible Option

Gayatri Nangia; Kelly Borges; K. Rajender Reddy

Disclosures

J Viral Hepat. 2019;26(12):1362-1371. 

In This Article

Abstract and Introduction

Abstract

Due to the unfortunate epidemic of opioid overdose deaths among people who inject drugs (PWID) in North America, there has been an increase in the availability of hepatitis C (HCV)-positive organs for transplantation and consequently the potential to decrease waiting times for solid organ transplantation if an HCV-uninfected recipient is willing to accept an HCV-positive donor. The confidence in this potential new strategy comes as a result of the advent of safe and highly effective pan-genotypic direct-acting antivirals (DAAs). This promising strategy has been the most widely studied in kidney transplantation. Liver transplantation has positive results preliminarily, but has even less available data because viable HCV-infected donor livers are typically transplanted into HCV-infected individuals. Further, while HCV-infected heart and lung transplantation, which face additional post-transplant issues, have shown encouraging results, these studies are small scale and are limited by short-term follow-up. Thus, it would be premature to implement this strategy as standard of care without large scale clinical and real-world trials and longer-term follow-up studies. Further, the ethics of this practice need to be considered. While some transplant professionals argue that more harm will be done by not utilizing HCV-infected organs, others contend that cautiously conducted multi-centre studies involving extensive post-transplant follow-up are paramount prior to endorsing widespread implementation of this strategy. The ethical permissibility of this practice hinges on whether access to DAA therapy can be secured in advance, and prospective recipients understand and accept all the risks associated with acquiring HCV.

Introduction

There are currently no policies or regulations governing the transplantation of HCV-positive organs into HCV-uninfected recipients.[1] However, there is a debate about whether the strategy of transplanting HCV-positive organs into uninfected patients should be implemented and if so, what regulatory oversight is necessary.[1]

This debate arises as a consequence of the unfortunate epidemic of opioid overdose in people who inject drugs (PWID).[2] In 2017, more than 70 000 drug overdose deaths occurred in the United States, 68% (47 600) of these involved an opioid.[3] Opioid overdoses are the main driver of the reported 9.6% increase in the age-adjusted rate of overdose deaths since 2016 (from 19.8/100 000 to 21.7/100 000).[3] Canada has also seen a rise in opioid deaths.[4] Between January 2016 and September 2018, there were 10 337 opioid-related deaths in Canada (from 8.4/100 000 to 11.8/100 000).[4] At the same time as this epidemic has spread, the waitlist for kidney transplantation has increased to over 100 000 people in the United States.[5] In many places in the United States, candidates spend over 5 years on the waitlist, often dying before transplantation.[5] The tragic increase in the number of deaths due to opioid overdoses has led to a rise in available organs for solid organ transplantation and consequently a decrease in waiting time, if an HCV-uninfected patient is willing to accept an HCV-infected organ.[6,7] Furthermore, aside from being HCV-infected, these donors are usually otherwise 'healthy'.[7] As evidence, livers from donors who suffered a drug overdose were associated with longer graft survival and deemed significantly better quality based on objective parameters.[7] The New England Organ Bank (NEOB), which has been attempting to maximize the use of suitable organs from donors who suffered from opioid overdose, reported a 254% increase in organ donations from people who suffered from a drug overdose and a 300% increase in transplants using HCV-positive donors.[6]

The confidence in this potential new strategy of transplanting HCV-positive organs is due to the advent of direct-acting antivirals (DAAs). Since 2011, HCV therapy has shifted from interferon-based therapy to DAAs, resulting in a significant increase in the efficacy and tolerability of HCV treatment. Increasing data have been gathered that support the safety and efficacy of using DAAs in the post-transplant period. However, there are some necessary considerations when using oral DAAs; for example, more data need to be gathered about how to deliver DAAs to patients who are intubated post-transplantation, an issue particularly applicable to those who are undergoing a heart or lung transplant. Additionally, the risk of viral breakthrough is a potential concern. The PWID population, in particular, has a higher prevalence of HCV genotypes 1a and 3, which have both been shown to be more difficult to treat.[8] HCV genotypes 1a and 3 are considered difficult to treat because they are associated with the most clinically significant baseline resistance-associated substitutions (RASs) to DAAs, particularly regimens containing NS5A inhibitors.[9] The extent to which these RASs may affect treatment outcomes varies by patient characteristics (eg presence of cirrhosis) and treatment regimen but nonetheless must be considered when discussing the risk of non-response, relapse, and viral breakthrough after patients have received a HCV-infected organ.[9] Another concern associated with HCV-positive organ transplantation is the uncommon but life-threatening complication of fibrosing cholestatic hepatitis (FCH) which can evolve within a short period after transplantation.[10] For liver transplant recipients with active HCV infection, the risk of fibrosing cholestatic HCV can be as high as 5%-10%.[11] Concerns also exist about drug interactions between DAAs and immunosuppressants, and severe renal insufficiency after transplantation that could contraindicate the use of sofosbuvir, one of the commonly used DAAs.[12–14] Additionally, the lack of standards governing recipient selection is a concern because there are no data on the outcomes of de novo HCV transmission post-transplant.[15] A kidney transplant candidate, for example, is not excluded from transplantation if they have diabetes. However, if that patient also has undiagnosed nonalcoholic steatohepatitis (NASH), they could be at an increased risk of experiencing severe liver injury if infected with HCV from a donor organ.[15]

Given the important ethical and medical considerations of using HCV-positive organs for transplantation, this review will define HCV-positive donor organs more precisely, outline the research that has been done on using such organs for kidney, liver, heart and lung transplantation, and discuss the ethics of this approach.

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