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Patients disease-free at 1 year following HCV-infected kidney transplant
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Patients who were negative for hepatitis C virus and received HCV-infected kidneys and antiviral treatment were clear of the disease and experienced good renal function up to a year after transplantation, according to study results recently published in the Annals of Internal Medicine.
“This pioneering trial involved transplanting kidneys from donors with [HCV] infection into recipients without HCV, followed by antiviral treatment,” Peter P. Reese, MD, MSCE, associate professor of medicine and epidemiology, University of Pennsylvania Perelman School of Medicine, told Infectious Disease News. “The 20 participants received a kidney transplant quickly, were able to avoid years of dialysis, had good quality of life and were successfully cured of HCV. Up to 1 year later, the kidney transplants functioned as well as kidneys from donors without HCV.”
Reese and colleagues conducted an open-label, nonrandomized trial of 20 HCV-negative candidates for kidney transplantation surgery. The patients received kidneys infected with genotype 1 HCV and were treated with elbasvir-grazoprevir 3 days after the surgery.
Ten patients were part of the Transplanting Hepatitis C Kidneys into Negative KidnEy Recipients (THINKER) trial, for which the researchers had reported 6-month outcomes in 2017. The study estimated 12-month HCV-treatment outcomes, estimated glomerular filtration rate (GFR) and quality of life for those patients. Ten additional transplants with kidneys from HCV-infected donors were performed, with 6-month data gathered for those patients.
HCV cure, defined as sustained virologic response at 12 weeks or undetectable HCV RNA 12 weeks after completion of HCV therapy, and adverse events attributable to HCV infection or therapy at 1-year follow-up were primary outcome measures. RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores and enrollment after transplantation, and post-transplant renal function in comparison with recipients of HCV-negative kidneys were exploratory outcomes.
“The aims of the study were to determine HCV treatment outcomes and adverse events in the expanded cohort of 20 patients, assess whether allograft function showed any evidence of durable injury from HCV, and describe trajectories in quality-of-life recipients after transplant of HCV-infected kidneys,” the researchers wrote.
The transplant recipients in the study had a mean age of 56.3 years (70% male, 40% black). Diabetes was the most common cause (45%) of end-stage renal disease. The 20 patients underwent transplant with HCV-infected kidneys of 15 donors.
The researchers reported that the transplant recipients in the study were anticipated to have prolonged waiting times for HCV-negative kidney transplants and were less likely to have conditions that would elevate the risk for liver disease, death or allograft failure after transplant.
All transplant recipients achieved a 100% HCV cure rate. The patients experienced a decrease in mean PCS and MCS quality-of-life scores at 4 weeks. In subsequent measurements, PCS scores increased above pre-transplant values, and MCS scores were similar to baseline values.
When participants of the THINKER study were compared with recipients of HCV-negative kidneys at 6 months, eGFRs were similar (median, 67.5 vs. 66.2 mL per minute/1.73 m2; 95% CI for between group difference, –4.2 to 7.5 mL per minute/1.73 m2). Results also were similar at 12 months (median, 72.8 vs. 67.2 mL per minute/1.73 m2; CI for between-group difference, –7.2 to 9.8 mL per minute/1.73 m2).
“Because of the opiate crisis, many organ donors have hepatitis C,” Reese said in the interview. “Kidneys from deceased donors with hepatitis C are valuable and can improve the lives of patients who are suffering on dialysis. Well-informed patients and their doctors should know that accepting organs from donors with hepatitis C may be worth considering to get the benefits of transplant.”
In a related editorial Adnan Sharif, MBChB, MD, of Queen Elizabeth Hospital and University of Birmingham in Birmingham, United Kingdom, wrote that the study results “confirm the growing consensus that, in the current era of [direct-acting antivirals (DAAs)], utilization of HCV-positive kidneys in HCV- negative recipients is feasible.”
He noted that there are challenges to the procedure, including financial reimbursement for DAA therapy.
“Reese and colleagues’ study should encourage workable strategies to increase utilization of HCV-positive kidneys (and other organs) in transplant candidates regardless of their HCV serostatus, thereby offering hope to thousands in need of life-saving or life-enhancing transplants,” Sharif concluded. – by Bruce Thiel
Disclosures: Reese reports grants from Merck, CVS Caremark, AstraZeneca and Bristol-Meyers Squibb and other financial support from the American Journal of Kidney Diseases outside the submitted work. Sharif reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Organ transplantation is lifesaving and has extended the lives of thousands of patients globally. But we cannot keep up with demand.
More than 120,000 individuals in the United States alone are on the waiting list today. Yet hundreds of scarce organs are discarded every year because of fear of transmitting infections to recipients, resulting in poor outcomes. This is either because several known donor infections are challenging to treat after transplant surgery, or undiagnosed infections in potential donors thwart a reliable treatment plan in newly immunosuppressed recipients.
The development of potent direct-acting antiviral agents has led to our ability to cure HCV in recent years, promising to make many previously discarded HCV-infected organs now safe to use.
This study by Reese and colleagues inches us closer to prime-time use. And because of this study, we can now have more clarity about 1-year outcomes when we counsel patients, not just in terms of mortality and ability to cure, but also kidney function and quality of life.
However, there are several caveats when thinking about generalizing these rosy study findings to all HCV-infected donors and patients in clinic. The first is that HCV donors in the study were relatively young and had healthy kidneys with favorable kidney donor profile index scores (lower chance of graft failure based on donor characteristics). Also, HCV- infected donors usually have concomitant risk for other bloodborne pathogens like HIV and hepatitis B virus; these are treatable but not curable. Donors are generally tested for a battery of infectious diseases before transplant surgery, but risk for HIV and HBV poses some unique challenges. Because of a potential window period where diagnostic tests may be potentially falsely negative, recipients of these organs will need to have periodic follow-up testing after transplantation has occurred. Risk for disease transmission is exceedingly small in the case of negative donor molecular testing, but some patients may be concerned given the stigma of potentially contracting these infections.
Although we can likely extend these findings to many other solid organs such as hearts and lungs, we need additional guidance around variables such as the degree of liver fibrosis in donors before we can use HCV- infected livers widely.
The last and probably most important consideration is financial. Study participants were guaranteed coverage of otherwise prohibitively expensive HCV treatment regimens after transplant surgery. This is not always the case in real life. Current payment for these antivirals is based on a heterogeneous and shifting hodgepodge of state, country and health insurance plan policies, and patients may be saddled with no reimbursement or expensive copays. So are we ready for “mainstream use” — as the Annals of Internal Medicine editorialist for this study provocatively declares? Soon, but not just yet. But if this study inches insurance plans and states closer to guaranteeing full payment for HCV treatment in more infected individuals, we can open the floodgates for more widespread use of these valuable organs.
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