'Real-life' experience with direct-acting antiviral agents for hepatitis C virus in end-stage renal disease

Int J Artif Organs. 2018 Jul;41(7):363-370. doi: 10.1177/0391398818763478. Epub 2018 Mar 27.

Abstract

Background and aims: The advent of direct-acting antiviral agents promises to change the management of hepatitis C in patients with end-stage renal disease, a patient group where the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' group of patients with end-stage renal disease.

Methods: We performed a single-arm, multi-centre study in a cohort (n=30) of patients with advanced chronic kidney disease (mostly on dialysis) who underwent antiviral therapy with direct-acting antiviral agents. The primary end-point was sustained virologic response (serum hepatitis C virus RNA < 15 mIU/mL, 12 weeks after treatment ended). We collected data on on-treatment adverse events, serious adverse events and laboratory abnormalities.

Results: In total, 23 (77%) and 7 (23%) patients underwent regular dialysis and had chronic kidney disease at pre-dialysis stage, respectively. Six regimens were adopted: elbasvir/grazoprevir ( n = 6), ledipasvir/sofosbuvir ± ribavirin ( n = 4), PrOD regimens ± ribavirin ( n = 10), simeprevir + daclatasvir ( n = 3), sofosbuvir + daclatasvir ± ribavirin ( n = 3), sofosbuvir + ribavirin ( n = 4). The SVR12 rate was 90% (95% confidence interval, 74%; 96%). A total of 27 (90%) patients achieved SVR12; there were three virologic failures - two were non-responders and one had a viral breakthrough while on therapy. Adverse events occurred in 53% (16/30) (95% confidence interval, 0.39; 0.73) of patients and were managed clinically without discontinuation of therapy or hospitalization. The most common adverse event was anaemia ( n = 12) that required blood transfusions in seven individuals; deterioration of kidney function occurred in one (14%).

Conclusion: All-oral, interferon-free therapy with direct-acting antiviral agents for chronic hepatitis C virus in advanced chronic kidney disease was effective and well tolerated in a 'real-life' clinical setting. Careful monitoring of haemoglobin and serum creatinine during therapy with direct-acting antiviral agents is suggested. Studies are under way to address whether sustained viral response translates into better survival in this population.

Keywords: Antiviral agents; chronic kidney failure; dialysis; hepatitis C; renal dialysis.

MeSH terms

  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use
  • Carbamates
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Fluorenes / adverse effects
  • Fluorenes / therapeutic use
  • Hepacivirus
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Pyrrolidines
  • Renal Dialysis*
  • Retrospective Studies
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use
  • Simeprevir / adverse effects
  • Simeprevir / therapeutic use
  • Sofosbuvir / adverse effects
  • Sofosbuvir / therapeutic use
  • Sustained Virologic Response
  • Treatment Outcome
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / therapeutic use
  • Valine / analogs & derivatives

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Carbamates
  • Fluorenes
  • Imidazoles
  • Pyrrolidines
  • ledipasvir, sofosbuvir drug combination
  • Ribavirin
  • Simeprevir
  • Uridine Monophosphate
  • Valine
  • daclatasvir
  • Sofosbuvir