Rajesh Ruttala

IL-18 polymorphisms in hepatitis B virus related liver disease.

Interleukine-18 (IL-18) was originally called interferon (INF-γ) inducing factor and plays a critical dual role in Th1 polarization and viral clearance. We aimed to explore whether single-nucleotide promoter polymorphisms (SNPs) are associated with the outcome of hepatitis B virus (HBV) infection. 271 HBV infected patients were recruited in this study out of these 109 were spontaneously recovered and 162 were diagnosed to be having persistent HBV infection which includes 48 chronic hepatitis, 84 liver cirrhosis, 30 HCC cases and were compared with 280 healthy controls. IL-18 promoter genotyping was performed with sequence-specific primers. The results demonstrated the significant involvement of genotype AA at position -607 in healthy controls (38.6%) when compared to cases (26.0%) (OR=0.54 (0.385-0.797)) and also associated with spontaneous clearance (37.6%) compared to persistent HBV infections (17.9%) (OR=2.76 (1.582-4.832)). Whereas, genotype CC at position -607 in cases (18.0%) when compared to healthy controls (6.7%) (OR=3.03 (1.734-5.303)) also associated with persistent HBV infections (24.1%) compared to spontaneous clearance (9.2%) (OR=0.31 (0.151-0.67)). And genotype GC at position -137 in cases (49.5%) compared to healthy controls (38.5%) (OR=1.55 (1.11-2.18)). Whereas, genotype GG at position -137 in healthy controls (56.8%) compared to cases (45.4%) (OR=0.63 (0.451-0.885)). No significant difference at position -137 was observed between spontaneous clearance and persistent HBV infections. These polymorphisms of the IL-18 gene promoter region at position -607 and -137 could be associated with different outcomes of HBV infection. The people with allele A at position -607 may be protected against HBV infection; moreover AA genotype is associated with spontaneous clearance.

1001 EXPRESSION ANALYSIS OF NF-κB IN PATIENTS WITH ACUTE LIVER FAILURE DURING PREGNANCY

Background and Aims: There is paucity of information on the pathophysiological mechanisms of the hepatic damage during acute liver failure caused by hepatitis viruses. Nuclear Factor Kappa B transcription factor, a key regulator of genes involved in response to infection, inflammation and stress leads to production of inflammatory cytokines and apoptotic stimuli. The study was aimed to determine any role of NF-uB in the death of acute liver failure women during pregnancy. Methods: A total of 60 patients were included in the study which constituted of 25 acute liver failure patients and controls consisting of 20 healthy blood donors, 10 healthy pregnant females and 5 autopsy cases. All the samples were subjected to serological analysis, PCR and nuclear protein extraction was carried out. Western blotting analysis was carried out to detect the expression of NF-uB using primary antibodies specific for p65 and p50 subunits. Results: Mortality rate in the pregnant female acute liver failure patient was very high 75% (9/12) but no significant difference was observed between the pregnant and nonpregnant patients. The expression of p50 protein in blood was very high78.94% (15/19) in the HEV infected acute liver failure cases while in majority of the cases 52.89% (11/19), p65 showed nil expression in the HEV infected cases. In the pregnant acute liver failure patients, expression of essential p65 was nil in 58.3% (7/12) cases and low in majority 60% (6/10) of the healthy pregnant patients showing nil expression in the HEV infected cases. The expression of p50 protein was very high in 6 cases (6/10, 60%) of the post mortem liver tissue whereas 3 (3/5, 60%) controls showed normal expression whereas in the surviving cases moderate expression of p50 was observed in the blood of all the six cases compared to p65 which showed low to nil expression in all the cases. Conclusion: p65 is an essential component for normal functioning of the NF-uB complex and its absence causes increased apoptosis and liver degeneration leading to liver damage and death in acute liver failure patients confirming the anti-apoptotic role of NF-uB.