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

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.