Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular
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- Category: Vol. 77, June 2009
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Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Expression of Interferon Regulatory Factor-1 (IRF-1),ABD EL-RAHMAN N. ZEKRI, RABAB A.N. MOHARRAM, ABEER A. BAHNASSY, HANAA M. ALAM EL-DIN, AHMAD NABIL LOTFY HASSAN, ZEINAB K. HASSAN, NAGLAA A. ZAYED, HESHAM EL- MAKHZANGY, ASHRAF O. ABDEL-AZIZ and GAMAL ESMAT
Abstract
Background/Aim: Infection with hepatitis C virus (HCV) frequently results in a persistent infection, suggesting that it has evolved efficient mechanism(s) for blocking the host cell's innate antiviral response. The immune response to virus infection results in activation or direct induction of the inter-feron regulatory factors (IRFs), which are a family of proteins involved in the regulation of interferon (IFN) and IFN inducible genes. IRF3 and IRF7 have been demonstrated to play an essential role in virus-dependent signaling, whereas IRF1 is critical for proper IFN-dependent gene expression. The current study has been performed to show the expression profile of interferon regulatory factors (IRF-1, IRF-3, and IRF-7) in Egyptian patients with HCV-related liver diseases and hepa-tocellular carcinoma (HCC).
Material and Methods: This study included 90 patients, who were positive for HCV infection by RT-PCR, divided into three groups: Group I included 30 patients with chronic hepatitis C, Group II included 30 patients with liver cirrhosis in addition to Group III of 30 patients with HCC. RT-PCR analysis was done to determine the expression profile of IRF-1, IRF-3, and IRF-7 genes extracted from the peripheral blood mononuclear cells of those patients.
Results: IRF-1 expression was significantly higher (p< 0.001) in patients of Group I (86.6%) compared to those in Group II (46.7%) and Group III (36.7%), while IRF-3 expres-sion was significantly higher (p<0.005) among patients of Group II (73.3%) in comparison to that in Group I (50%) and Group III (36.7%). On the other hand, although expression of IRF-7 was higher in Group II than in the other groups, there was no statistically significant different (p>0.05).
Conclusions: Alterations in IRFs expression might be considered as markers associated with a higher risk of cirrhosis in patients with chronic HCV infection. Expression of IFR-1 and IFR-3, were more prevalent in patients with chronic HCV and cirrhosis respectively in comparison to HCC patients. Thus, IRF-1 could be nominated as one of the tumor suppressor factors and could aid in the early detection of HCC.