Hepatitis C Infection May Be a Blessing for Patients in Need of a Transplant

For many patients, receiving an organ from an HCV-positive donor is the best option

“We are very proactive about our hepatitis C patients,” says Uttam Reddy, MD, medical director of the kidney transplant program at the University of California, Irvine (UCI) Medical Center. This is because in Southern California, the average wait time for a hepatitis C virus (HCV)-negative organ is 8 to 10 years. If, however, a patient with HCV is willing to receive an HCV-positive organ, the typical wait time is less than two years, a difference that Dr. Reddy describes as a “notably significant benefit.” In fact, he adds, “Before treating HCV in patients with advanced kidney disease, we recommend that they be evaluated at UCI first to assess the degree of their liver disease. If their liver disease is not advanced, we recommend proceeding with transplant and then treating their HCV after transplantation.”

Although larger programs routinely transplant HCV-positive kidneys, smaller programs tend not to, and this, according to Dr. Reddy, is a “major disservice” to patients. He acknowledges, however, that these smaller centers’ more conservative approach likely stems from the high level of regulation in the transplantation field: Whereas transplantation centers may more easily absorb the incremental risk of transplanting HCV-positive organs, smaller centers are under pressure to take as few risks as possible. Patients, however, suffer from the consequences of this risk-averse approach to transplantation.

The transplantation of HCV-positive organs into HCV-positive patients appears to be safe, but there are theoretical risks. For example, the organ may be infected with a different strain of virus from the one that infects the recipient, in which case the transplant could theoretically complicate treatment of the recipient's infection. In most cases, transplant providers do not know the donor's HCV strain and are thus unable to protect against this potential consequence. Although such a risk may seem trivial to a patient facing a decade of dialysis, patients who anticipate only a year on the waitlist before they can receive an HCV-negative organ may decide to forgo the incremental risk.

Pushing Boundaries, Gauging Risks

Dr. Reddy and others in transplantation view the successful treatment of HCV as the biggest breakthrough in healthcare in recent decades. Moreover, Dr. Reddy feels that the existence of direct-acting antivirals (DAAs) may be a “game changer” for patients who require a kidney transplant. When he first arrived at UCI, the rate of transplant of HCV-positive organs was quite low; many of the nephrologists did not even realize that the wait time for HCV-positive patients could be dramatically shorter. Dr. Reddy worked to educate both nephrologists and patients. He pointed out that for most patients, a one-year delay in treatment for HCV would likely not affect the course of disease, whereas a decade on dialysis would not be, as Dr. Reddy put it, “a safe bet.” This message was well received by the UCI hepatology team and its patients and, from that point on, approximately 5 to 10% of the transplanted organs at UCI have been HCV-positive.

“We were encouraging patients not to get treated for HCV until they were first evaluated at UCI,” Dr. Reddy says. “We were aggressive about it.”

The results speak for themselves. “We had two patients who were transplanted the first week we tried this,” reports Dr. Reddy. Kamyar Kalantar-Zadeh, MD, PhD, chief of nephrology at UCI, proudly describes the program as “a story of science and innovation and making correct decisions.”

John Gill, MD, professor of medicine at the University of British Columbia (UBC) Faculty of Medicine, plans to take the transplantation of HCV-positive organs one step further: UBC will soon be transplanting HCV-positive organs into HCV-negative patients, in effect exposing patients to infectious risk, and then treating the resulting infection. Although at first blush this may seem extreme, Dr. Gill says there is precedence: “There is a paradigm of using organs that we know have infections in patients who don't have infections,” he asserts.

Dr. Gill says that, in contrast to transplantation of a cytomegalovirus-positive organ, which is not a concern for most patients, there is often a stigma associated with HCV infection. “The reality is that, with the opioid crisis, people are worried about getting an organ from a drug user,” he says. Patients worry that an organ from such a donor may also be infected with HIV. “While there is risk with any organ,” Dr. Gill responds, “the advanced testing procedures we have now lower this risk so that it is much lower than continuing to wait on dialysis.” He adds that patients are also reassured when they learn about the efficacy of DAAs.

In Dr. Gill's experience, once patients have been educated and their questions have been answered, many choose to receive an HCV-positive kidney. Deirdre L. Sawinski, MD, assistant professor of medicine at the Hospital of the University of Pennsylvania (UPenn) in Philadelphia, agrees. UPenn is one of three transplantation centers in the United States that transplant HCV-positive organs into HCV-negative patients under an experimental protocol. She points to the overall lack of awareness that such a procedure is even possible, and adds, “The average person has not heard about it and doesn't know it is an option.” According to Dr. Sawinski's editorial in the American Journal of Transplantation, fewer than 50% of recipients with HCV are transplanted with HCV-infected kidneys, and less than half of transplant centers make use of these organs.1

The Time Is Ripe

There may only be a short window of opportunity to take advantage of HCV-positive organs. “Currently only 2.8% of deceased donor kidneys are [thought to be] HCV seropositive, but with the opioid epidemic, this number could be about 5.5%,” explains Bryce Kiberd, MD, a nephrologist, professor of medicine and director of the renal and pancreas transplant programs at the QEII Health Sciences Centre at Dalhousie University in Halifax, Nova Scotia. “That could mean there may be 700 infected kidneys available each year. If all were used,…about 5 to 15% of [patients] with HCV infection currently on the list could be transplanted within the year with a median wait time of less than 1 year.” Dr. Kiberd's recent analysis determined that such a strategy would be most beneficial for patients in regions with greater access to HCV-positive organs and/or those with very low anticipated HCV-positive–associated mortality.2 He adds that “The landscape is changing and the best approach is not the same everywhere.”

Dr. Reddy points out that as HCV becomes more frequently diagnosed, as DAAs become more widely available and, hopefully, as the opioid epidemic retreats, there will be fewer and fewer HCV-positive organs. So the conversation about HCV-positive organs is not about planning for the future. Instead, it is about optimizing the confluence of events that are occurring within what will probably be a small window of time. The transplantation community can seize this opportunity to save lives.

Meanwhile, Dr. Gill reminds us that because most physicians appropriately focus on their responsibility on the patient, members of the transplantation community bear an additional responsibility. “When a family donates organs of a loved one, their expectation is that we are going to try and make the maximum benefit of that gift,” he says. With that in mind, he encourages the transplantation community to accept that gift from individuals who are HCV positive and transform it into a blessing.

Update: Easement of Belatacept Prescribing Restrictions

In February 2017, Bristol Myers Squibb (BMS) sent a letter to physicians describing a manufacturing-related supply constraint for belatacept (Nulojix). They also announced the creation of the Nulojix Distribution Program, designed to ensure that patients who were currently taking the drug continued to receive treatment. To that end, physicians were required to register all existing patients in the Nulojix Distribution Program so they could receive unique identification numbers that would enable continued treatment.

In early 2017, BMS began to transition to a new manufacturing process with enhanced output, allowing BMS to accumulate inventory of belatacept. The combination of existing inventory and anticipated future production capabilities has enabled BMS to ease 2017 prescribing restrictions. The company notes, however, that belatacept remains on lists of drug/medicine shortages, and it may again become necessary to implement appropriate actions, such as reinstitution of tighter restrictions, to ensure a continuous supply of belatacept for patients who have started therapy.

In conclusion, BMS suggests that initiation of treatment with belatacept in new patients be considered on a case-by-case basis and used when alternative therapeutic options are less appropriate, while available supplies allow continuous treatment for patients who have started therapy.