Paritaprevir/Ritonavir/Ombitasvir Plus Dasabuvir Regimen in the Treatment of Genotype 1 Chronic Hepatitis C Infection in Patients with Severe Renal Impairment and End-Stage Renal Disease: a Real-Life Cohort

Kidney Blood Press Res. 2018;43(2):594-605. doi: 10.1159/000488965. Epub 2018 Apr 13.

Abstract

Background/aims: Chronic hepatitis C (HCV) virus infection reactivates under immunosuppressive drugs and therefore has a negative impact on long-term survival of kidney transplant recipients. Treatment-induced clearance of hepatitis C virus (HCV) in kidney transplant candidates prevents virus reactivation after transplantation. Paritaprevir/Ritonavir/Ombitasvir with Dasabuvir (PrOD) represents a highly effective treatment regimen for HCV genotype 1 (GT1), also suitable for patients with end-stage renal disease (ESRD). Serious drug-drug interactions may represent a limiting factor of this regimen. The aim of this retrospective study was to evaluate safety, efficacy and drug-drug interactions management associated with PrOD treatment in the Czech real-world cohort.

Methods: Emphasizing concomitant medication adjustment, we described the treatment course with PrOD regimen in 23 patients (4 with CKD4 and 19 on maintenance haemodialysis) infected with HCV GT1 (21 GT1b, 2 GT1a), 18 males and 5 females with an average age of 53.7 years. Six patients had compensated liver cirrhosis and 3 of them were liver transplant recipients.

Results: All 23 patients completed the 12-week treatment and achieved sustained virological response 12 weeks after the treatment (SVR12 rate 100%). None of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, hypotension, diarrhoea, and hyperkalemia. Four patients presented with a serious adverse event unrelated to the antiviral drugs (salmonellosis, non-functional kidney graft rejection, early gastric cancer, renal cyst infection, initiation of haemodialysis). Concomitant medication had to be modified with the treatment initiation in 10 out of 23 (43.5%) patients (calcium channel blockers, ACE inhibitors, statins, diuretics, tacrolimus); four patients required further adjustment of antihypertensive drugs or tacrolimus dosage on-treatment.

Conclusion: PrOD regimen demonstrated an excellent efficacy and good tolerability. Both prospective adjustment of concomitant medication and further on-treatment adjustment allowed for a safe treatment course.

Keywords: Dasabuvir; Genotype 1; Haemodialysis; Hepatitis C; Ombitasvir; Paritaprevir.

MeSH terms

  • Anilides / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Carbamates / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Kidney Failure, Chronic / therapy
  • Kidney Failure, Chronic / virology*
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Renal Insufficiency / therapy
  • Renal Insufficiency / virology*
  • Ritonavir / therapeutic use
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use

Substances

  • ABT-267
  • ABT-333
  • ABT-450
  • Anilides
  • Antihypertensive Agents
  • Antiviral Agents
  • Carbamates
  • Macrocyclic Compounds
  • Sulfonamides
  • Uracil
  • Ritonavir