Real life rates of sustained virological response (SVR) and predictors of relapse following DAA treatment in genotype 3 (GT3) patients with advanced fibrosis/cirrhosis

PLoS One. 2018 Jul 31;13(7):e0200568. doi: 10.1371/journal.pone.0200568. eCollection 2018.

Abstract

Background: Treatment of GT3 remains challenging compared to other genotypes.

Aims: To explore real life SVR rates and to identify predictors of virological failure across the most recently used Direct acting antiviral (DAA) regimens in a large cohort of Italian patients with cirrhosis or advanced fibrosis (F3 or F4).

Methods: Between May 2015 and June 2017, the combinations of sofosbuvir (SOF) plus daclatasvir (DCV) ± RBV and SOF plus velpatasvir (VEL) ± RBV become available in our Country. Patients were treated following Italian guidelines within a protocol implemented by 11 centers working together on genetics.

Results: Of 336 patients, 38.1% were Peg/IFN-experienced. SOF/DCV was used in 65.1%, SOF/VEL in the remaining. Overall SVR12 was 90.2% ranging from 87.2% after SOF/DCV to 95.7% after SOF/VEL (p = 0.012). No additional benefits of RBV use were observed for both regimens. 155 patients (46.1%) had cirrhosis. SVR12 was 87.1% (135/155) for cirrhotic patients and 92.8% (169/182) for non-cirrhotic (p = 0.09). NS5A-RASs were present at baseline in 6.4% of patients, PNPLA3GG and IL28BCC genotypes in 7.3% and 33.0%, respectively. No association between favorable genetics and SVR12 was observed. Predictors of relapse were: history of Peg/IFN/RBV failure (OR = 6.34, 95% CI 2.04-19.66, P = .001), baseline NS5A-RASs (OR = 8.7, 95% CI 1.58-47.92, P = 0.013) and treatment regimen (OR = 5.57 95% CI 1.64-18.95.96, P = 0.006).

Conclusions: Our real-world results validate the efficacy of current GT3 IFN-free regimens suggesting that, among patients with severe disease, Peg/IFN/RBV experience and NS5A associated RASs are predictors of relapse. Their relevance can be expected to decline with the use of SOF/VEL. (250).

Publication types

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

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Imidazoles / administration & dosage*
  • Italy
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / virology
  • Polymorphism, Genetic
  • Prospective Studies
  • Recurrence
  • Ribavirin / administration & dosage*
  • Sofosbuvir / administration & dosage*
  • Sustained Virologic Response*

Substances

  • Antiviral Agents
  • Imidazoles
  • Ribavirin
  • daclatasvir
  • Sofosbuvir

Grant support

Alessandra Mangia served as speaker/consultant: Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp and Dohme, Roche. We received funding from commercial sources including Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp and Dome, Roche. The study was funded by “Casa Sollievo della Sofferenza”, RC 2017 to Dr. Alessandra Mangia. The specific roles of these authors are articulated in the 'author contributions' section. These funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.