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


METHODS
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.


CONCLUSIONS
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.
Clinical Pathology Department, University of Alexandria, Alexandria, Egypt. doaa_hashad2003@yahoo.com
Doaa I
DI
Hashad
Perihan E
PE
Salem
Dina M
DM
Abdallah
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008099:Liver; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a