Treatment and management options for the hepatitis C virus infected kidney transplant candidate

Abstract

A substantial body of literature has unequivocally established that prevalent hepatitis C virus infection in chronic kidney disease (CKD), end stage renal disease (ESRD) and kidney transplant recipients is associated with a negative impact on patient survival. As a consequence of remarkable work that explained the details of the hepatitis C virus (HCV) genome, a class of drugs referred to as the direct-acting antiviral (DAA) agents were developed that targeted specific key sites in viral replication. Large clinical trials in the HCV-infected general population followed soon after that demonstrated cure rates exceeding 95%. Treatment paradigms have been further refined and expanded to populations of patients that were initially excluded from the large pivotal trials. This includes the CKD and ESRD patients for whom there are now safe and effective DAAs available as well. In this context, the focus of decision making has shifted from initially demonstrating safety and efficacy to now identifying which patient should receive therapy and at what point in their CKD/ESRD journey. The specific issue of timing of treatment is particularly relevant to the HCV-infected ESRD patient who is being considered for kidney transplantation. The option of treating with DAAs prior to the transplant or alternatively delaying therapy and treating in the posttransplant period will be influenced by several factors, including patient preference, the extent of liver injury, the availability of a living or deceased donor, and more recently the option of transplanting a kidney from HCV-positive donor. The latter has been associated with the advantage of shortened waiting times and expansion of the organ donor pool. The optimal timing and choice of therapy will be the result of a decision that has been individualized for each patient as a consequence of a process of clear communication involving the patient, primary care physician, nephrologist, gastroenterologist (GI)/hepatologist, and local transplant center.

The prevalence of hepatitis C and B among patients on hemodialysis and on renal transplantation waiting list in Poland has significantly decreased during the last 10 years

“…Thus, the cure of HCV in CKD stages 4–5, dialysis, and kidney transplant patients now seems possible, and the prevalence of HCV will likely decline rapidly in the near future. Moreover, the option of DAA treatment prior to transplantation has the advantages of shortened waiting times and expansion of the organ donor pool to include HCV+ donors [ 12 ]. However, there is a risk of DAA interaction with several other drugs, including calcineurin inhibitors [ 13 ]; thus, the timing of antiviral therapy for waitlisted patients (before vs after transplantation) should be decided in collaboration with the transplant center.…”

Treatment with Grazoprevir/Elbasvir in Post-kidney Transplant Patients with Hepatitis C Virus Genotype 4 Infection

“…The use of DAAs in patients with chronic kidney disease means that treatment can often be successful before the need for transplantation. Delaying therapy and providing treatment during the post-KT period is also an option that can be influenced by several factors, including patient preference, the extent of liver injury, the availability of a living or deceased donor, and the option of transplanting a kidney from an HCV-positive donor with a potentially short waiting time and expanded organ donor pool (34).…”

Direct acting anti‐viral medications for hepatitis C: Clinical trials in patients with advanced chronic kidney disease

“…Several papers and the recently published KDIGO guidelines have suggested DAA treatment options in CKD and ESRD, including for patients with compensated cirrhosis, and have proposed pretransplantation and posttransplantation treatment algorithms . Some of these recommendations, in particular, prioritizing HCV positive deceased donor kidneys for HCV positive wait‐listed patients in order to reduce waiting time, are more appropriate in the United States where there is presently a long waiting period for deceased donor kidneys and an expanded pool of HCV‐infected donor organs due to the opioid epidemic.…”