Toll like receptor 3 expression as a novel predictor of response to treatment in chronic hepatitis C virus patients

Scand J Clin Lab Invest. 2011 Dec;71(8):641-6. doi: 10.3109/00365513.2011.624196. Epub 2011 Oct 24.

Abstract

Purpose: This work was carried out to study the level of pretreatment hepatic expression of Toll like receptor 3 (TLR3) among chronic HCV patients, aiming to determine if there are consistent differences in gene expression, between those who show complete early virological response (cEVR) at week-12 of Pegylated-Interferon α-2a plus ribavirin treatment and others who are not responding to this combination, also if this could be used to predict treatment outcomes.

Method: A total of 61 chronic hepatitis C patients were enrolled in the study. For all of them, baseline hepatitis C virus (HCV) viral load was determined and TLR3 gene expression was examined in their hepatic percutaneous needle biopsy specimens using a real time-polymerase chain reaction technique. Hepatic TLR3 was also traced using immunohistochemistry. All patients followed a 12-week regimen of Pegylated-Interferon α-2a plus ribavirin then post-treatment viral load was assayed.

Results: Hepatic expression of TLR3 was significantly increased in the non-responder group as compared to those who showed complete early virological response to the used treatment regimen. Using receiver operator characteristic (ROC) curve analysis, a cutoff level of 1.5 was set for TLR3 expression to distinguish responders from non-responders to the 12-week treatment regimen used.

Conclusion: In conclusion, measuring the hepatic expression of the interferon stimulated gene, TLR3 could provide a new molecular marker for pre-treatment prediction of complete early viral clearance, thus helping in patients' selection and optimizing treatment outcomes.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / therapeutic use
  • Biomarkers / metabolism*
  • Biopsy
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Drug Therapy, Combination
  • Female
  • Gene Expression
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / growth & development
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / therapeutic use
  • Liver
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / therapeutic use
  • Predictive Value of Tests
  • RNA, Viral / analysis*
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Ribavirin / administration & dosage*
  • Ribavirin / therapeutic use
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 3 / metabolism*
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • Biomarkers
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a