Changes of inflammatory cytokines/chemokines during ravidasvir plus ritonavir-boosted danoprevir and ribavirin therapy for patients with genotype 1b hepatitis C infection

J Med Virol. 2020 Dec;92(12):3516-3524. doi: 10.1002/jmv.26161. Epub 2020 Jun 29.

Abstract

This study investigated the safety and efficacy of ravidasvir (RDV) plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimens for treatment-naïve non-cirrhotic patients with hepatitis C virus (HCV) genotype 1b in mainland China. We also gained insight into HCV-host interactions during anti-HCV treatment. 16 patients with HCV and 10 healthy people enrolled the study. Three of 16 patients received 12-weeks' placebo treatment first and served as the placebo controls. All (n = 16) patients received 12-weeks' RDV plus DNVr and RBV treatment. The adverse effects (AEs), viral loads, alanine transaminase, and aspartate aminotransferase were recorded during study. We also performed multianalyte profiling of 48 cytokines/chemokines in 16 patients with HCV and 10 normal controls. Seventy-five percent patients treated with RDV plus DNVr and RBV experienced AEs. No death, treatment-related serious AEs or AEs leading to discontinuation were reported. The serum HCV-RNA levels remained extremely high in 3 placebo controls after treated with placebo. After RDV plus DNVr and RBV treatment, all patients achieved sustained virologic response (SVR) at posttreatment week 12, but 1 patient experienced viral relapse at SVR 24. The cytokine/chemokine expression pattern was markedly altered in patients with HCV as compared with healthy controls. The interferon-inducible protein-10 (IP-10) decreased after anti-HCV treatment, and dramatically increased in one patient with viral relapse. The regimen of RDV and DNVr plus RBV represents a highly safe and effective treatment option for HCV patients in mainland China. The IP-10 has the potential to be an indicator of innate immune viral recognition.

Keywords: danoprevir; hepatitis C virus; interferon-inducible protein-10; ravidasvir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents* / therapeutic use
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / therapeutic use
  • China
  • Cyclopropanes*
  • Cytokines* / blood
  • Drug Therapy, Combination*
  • Female
  • Genotype*
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / virology
  • Humans
  • Isoindoles* / therapeutic use
  • Lactams / therapeutic use
  • Lactams, Macrocyclic*
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Proline* / analogs & derivatives
  • Proline* / therapeutic use
  • RNA, Viral / blood
  • Ribavirin* / therapeutic use
  • Ritonavir* / therapeutic use
  • Sulfonamides* / therapeutic use
  • Sustained Virologic Response
  • Treatment Outcome
  • Valine
  • Viral Load / drug effects

Substances

  • Ribavirin
  • Antiviral Agents
  • Proline
  • Lactams, Macrocyclic
  • Cyclopropanes
  • Sulfonamides
  • Isoindoles
  • Cytokines
  • danoprevir
  • Ritonavir
  • Lactams
  • Benzimidazoles
  • Placebos
  • RNA, Viral
  • Valine