INTERFERON SIGNALLING PATHWAY: INTRAHEPATIC EXPRESSION OF STAT1 IN INTERFERON RESISTANT HEPATITIS C PATIENTS

Abstract

Objective: to investigate the role of STAT1 in treatment failure in interferon resistant hepatitis C virus (HCV) infected patients. Methodology: Liver biopsies and blood from patients infected with HCV, resistant to interferon therapy were collected under sterile conditions in the laboratory of Army Medical College, Rawalpindi. Study included HCV infected patients who were positive for serum HCV RNA, and were non-responders to two courses of interferon therapy, IFN-α injection and ribavirin oral for 24 weeks periods. Study also included 10 controls i.e. 5 normal healthy subjects with normal LFTs who were negative for anti-HCV antibodies and 5 responder patients who responded to first course of interferon treatment and had normal LFTs. The liver biopsy specimens were subjected to PCR based detection of STAT1 and liver histopathology status evaluation. GeneJET™ RNA Purification Kit# K0731, Fermentas was used for total RNA isolation from liver biopsy specimen. The study was approved by institute’s ethical committee. Results: STAT1 mRNA was detected in 96.2% (n=25/26) of the HCV patients resistant to interferon therapy and in 100% of the normal as well as responders. Patient’s distribution for histological activity index along with STAT1 mRNA expression was 68% in the score of 4-7 and 28% in the score of 8-12. Conclusion: STAT1 mRNA is being expressed by all the HCV infected patients resistant as well as responders to interferon therapy. STAT1 expression is not a major factor responsible for interferon resistance in HCV patients.