Relation between microRNA-21, transforming growth factor β and response to treatment among chronic hepatitis C patients

J Med Virol. 2019 Dec;91(12):2166-2173. doi: 10.1002/jmv.25559. Epub 2019 Aug 11.

Abstract

Background: Persistence of hepatitis C virus (HCV) infection and response to antiviral therapy has been shown to be associated with inappropriate levels of cytokines and microRNAs (miRNAs). miRNA levels have been reported to fluctuate during treatment. Thus they could be useful predictors for responses to treatment among HCV infected patients, thereby reducing ineffective treatments.

Aim: The current study aimed to investigate the relation between miRNA-21 expression profiles, transforming growth factor β (TGF-β) serum levels and response to treatment with the new direct antiviral drugs (sofosbuvir + daclatasvir ± ribavirin), among HCV infected Egyptian patients.

Subjects and methods: This prospective study was conducted on 50 HCV infected patients (before and after treatment) and 20 healthy volunteers. miRNA expression profiles were determined by real-time polymerase chain reaction and TGF-β1 serum levels were measured by using enzyme-linked immunosorbent assay.

Results: There was a significant increase in serum albumin, platelets count and a significant decrease in liver enzymes, serum bilirubin, and prothrombin time after treatment. Significant reduction of viral load among HCV patients after receiving the treatment was reported. Concomitantly, there was an increase in the relative quantity of miRNA-21 (P = .001*) and serum levels of TGF-β1 ( P = .337) among HCV patients after receiving treatment.

Conclusion: Nearly all responders to direct antiviral drugs showed increased levels of both miRNA-21 and TGF-β1. This may indicate an interplay between TGF-β1 and miRNA-21 during remission or progression of viral infection. Thus miRNA-21 could be used as promising serum biomarker, for assessment of antiviral treatment efficacy and improvement of fibrosis among chronically infected HCV patients.

Keywords: HCV; TGF-β1; daclatasvir; miRNA-21; sofosbuvir.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Carbamates
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / therapeutic use
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Prospective Studies
  • Pyrrolidines
  • Ribavirin / therapeutic use
  • Sofosbuvir / therapeutic use
  • Transforming Growth Factor beta / blood*
  • Treatment Outcome
  • Valine / analogs & derivatives
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • Biomarkers
  • Carbamates
  • Imidazoles
  • MIRN21 microRNA, human
  • MicroRNAs
  • Pyrrolidines
  • Transforming Growth Factor beta
  • Ribavirin
  • Valine
  • daclatasvir
  • Sofosbuvir