Executive Summary : | Chronic hepatitis B virus infection is a major public health problem which is responsible for over half a million deaths yearly worldwide mainly due to its late sequel of liver cirrhosis or hepatocellular carcinoma. The project enrolled a total of 679 subjects from three different geographical regions of northeast India. An interesting finding was that the proto-oncogene FOS gene has been found to upregulated moderately in CHB with HBeAg +ve (2.3 fold) while in cases HBV cases with Hepatocellular carcinoma it was found to be significantly upregulated (4.1 fold upregulation). Also, CD274 (Programmed Cell Death 1 Ligand 1) was found to be moderately upregulated (1.8 fold) in HCC cases with HBV. As expected IFN-G was found to be down regulated in chronic HBV infection (-1.9 fold) and also in HCC with HBV. Relative gene expression of Toll like receptors 1 to 10 (TLR 1 to 10) in PBMC were evaluated among cases and controls. It was observed that relative gene expression in PBMC of TLRs were not significantly altered in cases and control. In CHB with HBeAg positive subjects, TLR7 was found to be upregulated (2.8 fold). In HCC group with HBV, TLR2, TLR4, TLR7 and TLR8 were found to be upregulated above 2.5 fold but statistically not significant. Human proinflammatory cytokines, IL12p70, IL6, IL-8, IL-1B, IL-10 and TNF-A levels were quantitatively measured by flowcytometry. Among the cytokines measured, IL-12p70 was found to significantly low in CHB with HBeAg status compared to controls. Also, IL-8 was found to be moderately high in CHB (mean level 30.7 pg/ml) with HBeAg status compared to controls (21.13 pg/ml) however it was not significant statistically. In conclusion, the study reveals that chronic HBV infection does not significantly change the TLRs expression levels in PBMC apart from TLR7 and TLRs may not play a significant role in persistence of HBV infection in adulthood. However, the PPR adaptor MYD88 with moderate upregulation in CHB with HBeAg status will need further evaluation. An interesting finding of the study is that FOXP3 (master regulator of T-regulatory cells) and FOS is significantly upregulated in CHB with HBeAg status. As regulatory T-cells turns the immune response down, upregulation of FOXP3 may be playing a vital additional role in persistence of HBV infection. Further, low level of cytokine IL-12 in CHB may indirectly cause anti-viral cytokines like interferon-gamma to be not adequately produced by T-cells and NK cells which may play a role in persistence of HBV infection. Moreover, it was observed that HCC cases with HBV infection had a significant upregulation of the Protooncogene FOS. As FOS play a vital role in cell differentiation, transformation and proliferation, the role of FOS protein in HCC need to be further evaluated. The Tcell regulatory protein FOXP3 which was found to significantly upregulated in CHB with HBeAg positive status needs to be further assessed for its role in causation of persistence of HBV infection. |
Co-PI: | Dr. D. Biswas, Scientist, Regional Medical Research Centre (RMRC), Assam, Dr. U Devi, Scientist, Regional Medical Research Centre (RMRC), Assam, Dr. R K Phukan, Scientist, Regional Medical Research Centre (RMRC), Assam, Prof. A. K. Das, HOD, Department of Medcine, Assam Medical College and Hospital (AMCH), Assam, Dr. Tapan Majumdar, Associate Professor, Assam Medical College and Hospital (AMCH), Assam |