Pk Gumma

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.

Down regulation of TRIF, TLR3 and MAVS in HCV infected liver correlates with the outcome of infection†

In virus‐infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF), and TNF receptor associated factor (TRAF6) which induces interferon. Toll‐like receptor 3 (TLR3) induces activation of the NF‐kappa B (NF‐κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF, and TRAF6 outcome of HCV infection. The 46 chronic hepatitis C (CHC) patients were screened for LFT (Liver function test), HBsAg, Anti HCV, viral load, histology, and expression of TLR3, MAVS, TRIF, and TRAF6 genes. Out of 46 CHC patients, 7 were on therapy. The 12 healthy controls were screened for LFT, HBsAg, Anti HCV and gene expressions. The gene expressions were studied in liver tissue and measured using semi‐quantitative analysis of Western blots. It has been observed that the expression of TRAF6 was independent of HCV infection. The expression of TRIF, TLR3, and MAVS were significantly (P < 0.05) down regulated in CHC (N = 46) compared to healthy controls (N = 12), in high viral load (N = 21) compared to low viral load (N = 25), in HAI (Histology activity index) 1‐4 (N = 12), 5‐8 (N = 16), 9‐12 (N = 8), 13‐18 (N = 5) compared to HAI 0 (N = 5) cases. The significant reduction in the expression of TRIF, TLR3, and MAVS was observed in non‐responder (N = 3) compared to responder (N = 4) after treatment (P < 0.05). The HCV viral load was positively correlated with the disease severity. The down regulation of TRIF, TLR3, and MAVS expressions in CHC correlates with the disease severity and the outcome of HCV infection.

rs2230201 polymorphism may dictate complement C3 levels and response to treatment in chronic hepatitis C patients

The basis of response of chronic hepatitis C (CHC) patients to treatment is still unclear, and there may be many other factors which influence treatment outcome other than the existing ones. The serum concentration of C3 closely reflects the total complement activity, and individuals affected by C3 deficiency suffer from recurrent pyogenic infections. This study aims to find out relationship between levels of C3 in serum and its functional SNPs with response to treatment. The study included 132 CHC patients of which 48 received Pegylated IFN+Ribavirin and 81 controls. C3 levels and its three known functional SNPs genotyped by ELISA and SSP PCR, respectively. C3 Level of the healthy group was significantly higher (88.5 ± 19 mg/dL) when compared to CHC group (56 ± 18 mg/dL; P < 0.001). Thirty‐three of 36 responders were rs2230201 CC genotype carriers, whereas 9 of 12 nonresponders were non‐CC genotype. The ‘C’ allele of rs2230201 was found to be associated with increased serum C3 levels when compared to other genotypes in healthy group, whereas CT genotype was associated with lowered serum C3 in CHC group. A serum C3 value of <53 mg/dL was predictive of SVR with sensitivity 63.89% and specificity 66.67%. The study supports the observation that rs2230201 ‘C’ allele is associated with increase of serum C3 levels when compared to ‘T’ allele which may confer advantage in attaining SVR when present in homozygous condition. The study suggests that patients with serum C3 value <53 mg/dL and non‐CC genotypes may not respond to treatment.

7 CLINICAL SIGNIFICANCE OF CFH GENE POLYMORPHISM IN CHRONIC HEPATITIS C INFECTED PATIENTS

S 20TH ANNUAL CONFERENCE OF INASL, MARCH 2–4, 2012 S8

Role of Serum Interleukin-10 Levels in Patients with Chronic Hepatitis B Virus Infection from India

© 2011, INASL 6 Intrafamilial Occurrence of Hepatitis B Virus Infection and the Profile of Liver Disease in Close Relatives of Patients with HBV Infection R Kavitha, TM Ramachandran, T Varghese DM Trainee and Presenting Author, Additional Professor, Professor, Department of Gastroenterology, Government Medical College, Calicut, Kerala Aim: To evaluate the occurrence of HBsAg positivity in family members of HBsAg positive patients and to evaluate the burden of liver disease in these family members. Materials and Methods: All HBsAg positive patients who attended Gastroenterology Department, Calicut Medical College from January 2009 to December 2010 were studied. They were evaluated with HBeAg, anti-HBeAb, HBV DNA, LFT and USG abdomen. All first-degree relatives and relatives staying in the same house were screened for HBsAg. The relatives who tested positive were evaluated for disease activity. Results: There were 376 index cases in total: 230 males and 146 females, M:F = 1.57:1. Mean age – 32.8 years (6–76 years). Ninety six (25.53%) patients did not turn up after the initial visit. Among the remaining 280 patients, 48 (17.14%) were HBeAg positive. 60.27% of females were detected during antenatal screening. One hundred and fifty three patients (54.64%) had abnormal LFT, 21 (7.5%) had acute hepatitis, 46 (16.43%) had cirrhosis and 10 (3.57%) had HCC. Complete family screening was done for 173 cases (61.8%). Among the cases whose family members were screened, 95 (54.91%) had at least one family member seropositive. A total of 1115 family members were screened of which 162 (14.53%) were HBsAg positive. The relatives affected were brothers (26.01%) and sisters (19.08%); mothers in 10.40%, fathers in 10.98%, sons in 6.08%, daughters in 1.35%, second-degree relatives in 5.78% and 4.72% of spouses. Affected family members had LFT abnormality in 31/43 (72.09%), cirrhosis in 9.3% (4/43), and HCC in 1 patient. 27.9% (12/43) cases were HBeAg positive. Forty seven (16.79%) index cases were reluctant for family screening. Conclusion: The occurrence of hepatitis B positivity in family members of HBsAg positive patients was 14.53% which is 28-fold more than the community prevalence of HBV infection in our population which was only 0.52%. Brothers and sisters were more affected. Hence the infection among siblings and parents may be due to horizontal transmission. Conflict of Interest: None Role of Serum Interleukin-10 Levels in Patients with Chronic Hepatitis B Virus Infection from India R Ruttalla, PK Gumma, SK Polipalli, VK Karra, P Kar Department of Medicine, Maulana Azad Medical College, University of Delhi, India Background/Aims: Cytokines play a significant role in immune defense and may play an important role in the pathogenesis of chronic hepatitis B. Patients with chronic hepatitis B infection were evaluated to determine whether serum interleukin-10 (IL-10) levels were changed and whether the degree of these changes in serum levels correlated with HBV DNA levels. Methodology: Twenty nine patients diagnosed with chronic hepatitis B, 20 inactive HBsAg carriers, 20 liver cirrhosis and 18 healthy controls without any hepatitis marker positivity were included in the study. Serum IL-10 levels were measured by using commercially available ELISA kits as per the manufacturer instruction [Ray Biotech, Norcross]. The associations between liver pathology and HBV DNA levels were assessed. Result: IL-10 is elevated more in liver cirrhosis with positive HBeAg in comparison to asymptomatic carrier and control. The IL-10 levels calculated were: cirrhosis (53.60 ± 52.10), CHB (51.90 ± 37.1), HbsAg carrier (32.27 ± 22.10) and healthy (50.01 ± 43.03) pg/mL. Conclusion: IL-10 production is increased in liver cirrhosis patients with HBeAg positivity as compared to other groups (p < 0.05). However, as IL-10 is increased in liver cirrhosis with HBeAg positivity, the HBe antigen may be responsible for the raised IL-10 levels. Conflict of Interest: None Oral Plenary Session Expression Analysis of Proteins Inducing Interferon in Chronic Hepatitis C Patients P Kar, PK Gumma, S Medhi PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India Background: In virus-infected cells, pattern recognition receptors (PRRs) like toll-like receptor (TLR)-3 and RIG-I recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β (TRIF) which through TRAF6 induce the interferon. 03_JCEH-Abstract.indd 6 3/18/2011 11:13:03 AM