Hepatitis C virus infection in kidney transplantation‐changing paradigms with novel agents

Abstract

Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha-based therapies that were difficult to tolerate and were associated with adverse side-effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side-effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon-based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct-acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation.

Summary of the 2018 Kidney Disease Improving Global Outcomes (KDIGO) Guideline on hepatitis C in chronic kidney disease

“…In the context of high SVR rates across all studied CKD populations, strategies about the timing of treatment in CKD are of paramount importance . For instance, HCV‐infected kidney transplant candidates who are willing to accept the kidney from an HCV‐infected donor can lose their advantage of an often dramatically shorter wait‐list time if they choose to be treated pretransplantation (and, thus, no longer be eligible for an HCV‐infected kidney) . Conversely, delaying treatment until after transplantation increases the risk of posttransplant diabetes mellitus and HCV‐associated glomerulonephritis (GN) .…”

Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease

“…HCV infection prevalence in the hemodialysis (HD) population ranges from appropriately 3.6 to 15% in different countries [7,8]. Additionally, HCVassociated liver disease increases the risk of graft rejection, infection, and diabetes in patients receiving a kidney transplant [9][10][11], which indicated that eradication of HCV infection before transplantation would guarantee the transplantation success.…”

Transplantation of kidneys from HCV viremic donors to HCV viremic recipients followed by early direct acting antiviral therapy without ribavirin

“…The annual incidence of HCV in patients with end‐stage renal disease awaiting kidney transplant (KT) ranges from 1.4% to 2.1%, and the prevalence is estimated between 12% and 23% . HCV infection is associated with many adverse outcomes post‐KT, including an increased risk of acute rejection, chronic allograft nephropathy, diabetes and de novo glomerulonephritis …”

“…1 HCV infection is associated with many adverse outcomes post-KT, including an increased risk of acute rejection, chronic allograft nephropathy, diabetes and de novo glomerulonephritis. 2,3 Over the past several years, there has been a surge in HCV positive organs that are potentially available to the donor pool due to the growing opioid epidemic in the United States. In the last 5 years, the number of high-risk organ donors has increased and it is estimated that they make up 25% of the deceased donor pool.…”