Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C

J Hepatol. 2017 Apr;66(4):718-723. doi: 10.1016/j.jhep.2016.12.020. Epub 2016 Dec 28.

Abstract

Background & aims: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients.

Methods: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs.

Results: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004).

Conclusions: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy.

Lay summary: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

Keywords: Direct-acting antivirals; Hepatitis C; Immunosuppressive therapy; Liver transplant; Renal transplantation.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / physiopathology
  • Hepatitis C, Chronic / surgery*
  • Humans
  • Immunosuppression
  • Interferons / administration & dosage
  • Interferons / adverse effects
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Registries
  • Retrospective Studies
  • Spain
  • Sustained Virologic Response
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferons