Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection

PLoS One. 2016 Jul 14;11(7):e0158431. doi: 10.1371/journal.pone.0158431. eCollection 2016.

Abstract

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Simeprevir / adverse effects
  • Simeprevir / therapeutic use*
  • Sofosbuvir / adverse effects
  • Sofosbuvir / therapeutic use*
  • Transplant Recipients
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Ribavirin
  • Simeprevir
  • Sofosbuvir

Grant support

The authors received no specific funding for this work.