Background: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC). Objective: This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection. Materials: Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n = 15), inactive carriers (IC; n = 36), cirrhosis (Cirr; n = 25) and hepatocellular carcinoma (HCC; n = 12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry. Results: Significant reduction of HMGB1 and PARP1 gene expressions (P < 0.05) were observed in patients than controls with more explicit decline of PARP1 (P = 0.0002). Both genes were significantly downregulated (P < 0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P = 0.002) and HCC (P = 0.0006) while PARP1 declined significantly (P = 0.04) than HCC. Level of PgRNA was comparable in all the disease categories. Conclusion: In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC. ( J CLIN EXP HEPATOL 2013;3:89-95)

Regulated upon Activation Normal T cell Expressed and Secreted (RANTES) and interferon gamma inducible protein 10 (IP-10), both chemokines are chemotactic for immunocompetent cells and play an important role in cell mediated antiviral defense. The objective of this work was to assess the expression pattern of RANTES and IP-10 genes in peripheral blood mononuclear cells (PBMCs) of hepatitis B virus (HBV) infected patients having various ISSN 2157-6076 2012 www.macrothink.org/jbls 221 disease severity. The study was performed on 79 HBV infected patients grouped into acute, inactive carriers (IC), chronic (CHB), cirrhosis and hepatocellular carcinoma (HCC) plus 41 healthy voluntary blood donors as controls. Quantification of HBV surface antigen (HBsAg) was done by a sandwich enzyme linked immunosorbent assay (ELISA). Conventional and real time polymerase chain reaction (PCR) were used for genotyping and determination of HBV DNA load respectively. RANTES and IP-10 mRNA expressions were evaluated by reverse transcription PCR (RT-PCR) and densitometry. Results obtained show that RANTES expression reduced significantly (p<0.0001) in cirrhosis group in comparison to controls and remain unaltered in other disease categories. Reduction in IP-10 expression was significant (p=0.006) in patients of all disease categories than controls which was most evident in cirrhosis group (p<0.0001). No association was found between the expression level of chemokines with HBV genotypes, HBsAg and HBV DNA levels in sera. Journal of Biology and Life ScienceIt could be concluded that reduced expression of both the chemokines might be associated with lesser infiltration of immunocompetent cells to liver to avert further damage in cirrhosis.Serum level of both RANTES and IP-10 can be considered as prognostic marker of liver cirrhosis by validation studies.