Efficacy, Safety, and Predictors of Direct-acting antivirals in Hepatitis C Virus Patients with Heterogeneous Liver Diseases

New Microbiol. 2019 Oct;42(4):189-196. Epub 2019 Oct 14.

Abstract

Safety, efficacy, and predictor factors of sustained-virological-response after 24 weeks of new direct-acting antivirals were evaluated in hepatitis C virus patients with different stages of hepatic disease. 260 patients, median age 60 years, of whom 48.1% cirrhotics, 17.7% liver transplant recipients, and 45.7% naïve were treated with Sofosbuvir+Ribavirine, Sofosbuvir+Simeprevir±Ribavirine, Sofosbuvir+Daclatasvir± Ribavirine, Sofosbuvir+Ledispavir±Ribavirine, Ombitasvir/Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. Therapy outcomes, hematochemical parameters, viral replication, genotype, and resistance-associated-mutations were analyzed retrospectively. Sustained virological response was 90.4% in the whole population, 83.2% in cirrhotics, 85% in patients with previous virological failure, 93.6% in patients >60 years, and 95.6% in liver transplant recipients. SVR24 for each drug regimen was 75% Sofosbuvir+Ribavirine, 80.4% Sofosbuvir+Simeprevir±Ribavirine, 94.3% Sofosbuvir+Daclatasvir±Ribavirine, 98.7% Sofosbuvir+Ledispavir±Ribavirine, 100% Ombitasvir/ Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. The highest sustained virological response rates were obtained with genotype-1b (95.9%). Twenty-five patients, mostly cirrhotics or suffering from severe liver complications, manifested relapse (84%), breakthrough (12%), or non-response (4%). Mild side effects were observed in 41.1% of patients. Model-for-End-Liver- Disease score <10 and alanine aminotransferase ≤20 U/L at week 8 of therapy proved positive predictors of sustained virological response. Direct-acting antiviral therapy is efficacious and safe even in patients with advanced liver disease and/ or previous virological failure; Model-for-End-Liver-Disease <10 and alanine aminotransferase reduction during therapy were found to be reliable predicting markers of sustained-virological-response.

Keywords: Hepatitis C Virus (HCV); anti-HCV Direct-Acting Antivirals (DAA); combination therapy; viral resistance.

MeSH terms

  • 2-Naphthylamine
  • Antiviral Agents* / administration & dosage
  • Antiviral Agents* / standards
  • Biomarkers, Pharmacological / analysis
  • Cyclopropanes
  • Drug Therapy, Combination
  • Genotype
  • Hepacivirus
  • Hepatitis C* / drug therapy
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Lactams, Macrocyclic
  • Macrocyclic Compounds / administration & dosage
  • Middle Aged
  • Proline / analogs & derivatives
  • Retrospective Studies
  • Ribavirin / administration & dosage
  • Ritonavir / administration & dosage
  • Simeprevir / administration & dosage
  • Sofosbuvir / administration & dosage
  • Sulfonamides / administration & dosage
  • Treatment Outcome
  • Uracil / administration & dosage
  • Uracil / analogs & derivatives

Substances

  • Antiviral Agents
  • Biomarkers, Pharmacological
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Sulfonamides
  • Ribavirin
  • Uracil
  • Proline
  • Simeprevir
  • 2-Naphthylamine
  • dasabuvir
  • Ritonavir
  • paritaprevir
  • Sofosbuvir