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C POLYMORPHISM INFLUENCES THE OUTCOME OF CHRONIC HEPATITIS B VIRUS INFECTION IN HUMANS
05d: VIRAL HEPATITIS − d) HEPATITIS B − CLINICAL (EXCEPT THERAPY) HBV-genotypes were determined in HBsAg-positive patients; in these subjects we evaluated the stage and classified the infection as inactive carrier, mild or moderate/severe chronic hepatitis, cirrhosis and/or HCC. Results: Among the tested subjects, 144 (11.2%) resulted HBsAg-positive, and in 105/144 (72.9%) ALT-levels were elevated and serum HBV-DNA detectable. The genotype distribution was as follows: 65 genotype E (45.13%), 26 genotype D (18.1%), 22 genotype B (15.3%), 19 genotype C (13.2%), 7 genotype A (4.9%), 5 mixed genotypes (A-D) (3.5%). The evaluation of liver disease degree showed that 37/144 (25.7%) patients were inactive carriers, 66 (45.8%) had mild chronic hepatitis (mainly genotype E, 64.6%), 26 (18.1%) had a moderate/severe chronic hepatitis (mainly genotype D and C, 23.1% and 26.3%); 12/144 (8.3%) had cirrhosis and 3 (2.1%) presented HCC. Conclusions: Our study evidences a high prevalence of HBV-infection in immigrants, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus. The hepatitis B virus genotypes presented significant differences in epidemiological and clinical characteristics. 358 INTERLEUKIN 6 −174 G/C POLYMORPHISM INFLUENCES THE OUTCOME OF CHRONIC HEPATITIS B VIRUS INFECTION IN HUMANS E. Fornasiere1 , G. Fattovich2 , D. Bitetto1 , E. Fumolo1 , A. Cussigh1 , E. Fontanini1 , E. Falleti1 , R. Minisini3 , C. Fabris1 , M. Pirisi3 , P. Toniutto1 . 1 University of Udine, Udine, 2 University of Verona, Verona, 3 University of Novara, Novara, Italy E-mail: [email protected] Background and Aim: Interleukin-6 (IL-6) is a cytokine that possesses a pro-inflammatory activity and increases greatly following hepatic injury. IL-6 −174 /C polymorphism, influencing the degree of IL-6 expression, has been associated with a higher frequency of hepatitis C spontaneous resolution, while no association was found between this polymorphism and the outcome of hepatitis B virus (HBV) infection in far east patients. The present study aimed to verify the possible role of IL-6 −174 G/C polymorphism on the outcome of HBV infected patients. Methods: The study included 107 HBV positive consecutive patients (76 males), median age 52 years (range, 22−84) and 156 blood donors (113 males) median age 50 years (range 23−77). Twenty five blood donors were positive for only HBV anti-core antibody (HBcAb). Twenty-seven patients were found to be inactive HBV carriers while 80 had HBV related chronic hepatitis (18 of whom underwent liver transplantation). Genotyping for the IL-6 −174G>C polymorphism, that is associated with high IL-6 production, was performed on whole blood samples by a PCRrestriction fragment length polymorphism assay. Results: IL-6 −174 G>C allelic frequencies in patients and controls were G = 0.715 and 0.606, C = 0.285 and 0.394, respectively (p = NS). In both groups, no departure from the Hardy-Weinberg distribution was observed for each allele. A highly significant linear trend was observed for increasing frequencies of the IL-6 high producer genotypes (G/G+G/C) stratifying the population studied as follows: patients with resolved HBV infection (HBcAb+ blood donors) 6/25, HBV inactive carriers 3/27 and HBV positive chronic hepatitis 4/80 (p = 0.006). At multivariate analysis, IL-6 −174 G/G+G/C genotypes were found to be associated with a more severe outcome of HBV infection independently from the age and gender of the patients (p = 0.009). Conclusions: The IL6 −174 G>C polymorphism may play a role in the clinical evolution of HBV infection at least in European countries where a higher prevalence of the C allele was detected in comparison to the far east patients. Possessing a low IL-6 producer phenotype confers a genetic predisposition to a more favourable evolution and to an indolent course of HBV infection.
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359 INCREASE RISK OF HBeAg-NEGATIVE CHRONIC HEPATITIS B WITH OLDER AGE AT HBeAg SEROCONVERSION J. Fung, C.L. Lai, D.K.H. Wong, J. Yuen, M.F. Yuen. Medicine, University of Hong Kong, Hong Kong, Hong Kong S.A.R. E-mail: [email protected] Background: Recent evidence suggests that delayed HBeAg seroconversion is associated with poorer outcome. We aim to determine the incidence of HBeAg-negative chronic hepatitis B (CHB) according to the age at which HBeAg seroconversion occurs. Methods: Chronic hepatitis B patients with natural HBeAg seroconversion and over 12 months follow-up after HBeAg-seroconversion, and without complications, were included. Patients were followed 3−6 monthly with liver biochemistry. HBV DNA and liver stiffness measurements by transient elastography were determined at the time of last follow-up. HBeAgnegative CHB was defined as a combination of ALT elevation above the upper limit of normal on more than one occasion for the entire duration of follow-up after HBeAg seroconversion, and HBV DNA >5 log copies/mL. Results: In total, 228 patients were included with a median follow-up (after HBeAg seroconversion) of 103 months (range, 12–247), of which 118 (52%) were male. The median age was 42 years (range, 21−74). The median age at HBeAg-seroconversion was 32 years (range, 6−64). Seventy-five (33%) and 137 (60%) patients had HBV DNA >5 log and >4 log copies/mL respectively. HBeAg-negative CHB was identified in 51 (22%) patients. In patients with evidence of HBeAg-negative CHB, the median age at HBeAg conversion was significantly higher compared to those with persistently normal ALT or HBV DNA <5 log copies/mL (38 vs 31 years respectively, p < 0.001). In patients who seroconverted at age 20, 21−30, 31−40, 41−50, and >50, the rate of HBeAg-negative CHB was 12%, 15%, 21%, 39%, and 75% respectively (p = 0.002). There was no significant difference between males and females with respect to the age at HBeAg seroconversion (34 vs 32 years respectively, p = 0.90), and rate of HBeAg-negative CHB (25% vs 19% respectively, p = 0.25). Patients with HBeAg-negative CHB had higher median liver stiffness compared to those with persistently normal ALT or HBV DNA level <5 log copies/mL (9.0 vs 5.5 kPa respectively, p < 0.001). Conclusion: In Asian patients, older age at HBeAg seroconversion, but not gender, was associated with higher rate of HBeAg-negative chronic hepatitis B. Patients with HBeAg-negative CHB had a higher liver stiffness compared to those without evidence of active disease. 360 ASSOCIATION STUDY OF IFNAR2 AND IL10RB GENES WITH THE SUSCEPTIBILITY AND INTERFERON RESPONSE IN HBV INFECTION Q.-M. Gong1 , X.-F. Kong1 , Z.-T. Yang2 , J. Xu2 , L. Wang2 , X.-H. Li3 , D.-H. Zhang3 , J.-H. Jiang3 , X.-X. Zhang1,2,3 . 1 Department of Infectious Diseases, 2 Chinese-French Laboratory of Life Science and Genomics, 3 Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China E-mail: [email protected] Aim: Recent genome-wide association study discovered that two polymorphisms, interferon alpha receptor 2 (IFNAR-2) F8S and interleukin 10 receptor (IL-10RB) K47E, were associated with the susceptibility of hepatitis B virus (HBV) infection in Africa. Here, we reevaluate the effects of the two polymorphisms on HBV susceptibility in the Chinese Han population, and extend to study their association with interferon response in chronic hepatitis B. Patients and Methods: We included 341 patients with chronic hepatitis B (CHB) and 341 unrelated controls presenting with asymptotic HBV selflimited infection, who were well matched in age and sex. In the CHB group, 101 patients had been treated with peg-interferon alpha-2a for 48 weeks and followed up for 24 weeks to determine the clinical response, resulting 34 individuals with sustained virologic response (SVR) and 67 individuals with non-sustained response (NR). Subgroups in the CHB
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359 INCREASE RISK OF HBeAg-NEGATIVE CHRONIC HEPATITIS B WITH OLDER AGE AT HBeAg SEROCONVERSION J. Fung, C.L. Lai, D.K.H. Wong, J. Yuen, M.F. Yuen. Medicine, University of Hong Kong, Hong Kong, Hong Kong S.A.R. E-mail: [email protected] Background: Recent evidence suggests that delayed HBeAg seroconversion is associated with poorer outcome. We aim to determine the incidence of HBeAg-negative chronic hepatitis B (CHB) according to the age at which HBeAg seroconversion occurs. Methods: Chronic hepatitis B patients with natural HBeAg seroconversion and over 12 months follow-up after HBeAg-seroconversion, and without complications, were included. Patients were followed 3−6 monthly with liver biochemistry. HBV DNA and liver stiffness measurements by transient elastography were determined at the time of last follow-up. HBeAgnegative CHB was defined as a combination of ALT elevation above the upper limit of normal on more than one occasion for the entire duration of follow-up after HBeAg seroconversion, and HBV DNA >5 log copies/mL. Results: In total, 228 patients were included with a median follow-up (after HBeAg seroconversion) of 103 months (range, 12–247), of which 118 (52%) were male. The median age was 42 years (range, 21−74). The median age at HBeAg-seroconversion was 32 years (range, 6−64). Seventy-five (33%) and 137 (60%) patients had HBV DNA >5 log and >4 log copies/mL respectively. HBeAg-negative CHB was identified in 51 (22%) patients. In patients with evidence of HBeAg-negative CHB, the median age at HBeAg conversion was significantly higher compared to those with persistently normal ALT or HBV DNA <5 log copies/mL (38 vs 31 years respectively, p < 0.001). In patients who seroconverted at age 20, 21−30, 31−40, 41−50, and >50, the rate of HBeAg-negative CHB was 12%, 15%, 21%, 39%, and 75% respectively (p = 0.002). There was no significant difference between males and females with respect to the age at HBeAg seroconversion (34 vs 32 years respectively, p = 0.90), and rate of HBeAg-negative CHB (25% vs 19% respectively, p = 0.25). Patients with HBeAg-negative CHB had higher median liver stiffness compared to those with persistently normal ALT or HBV DNA level <5 log copies/mL (9.0 vs 5.5 kPa respectively, p < 0.001). Conclusion: In Asian patients, older age at HBeAg seroconversion, but not gender, was associated with higher rate of HBeAg-negative chronic hepatitis B. Patients with HBeAg-negative CHB had a higher liver stiffness compared to those without evidence of active disease. 360 ASSOCIATION STUDY OF IFNAR2 AND IL10RB GENES WITH THE SUSCEPTIBILITY AND INTERFERON RESPONSE IN HBV INFECTION Q.-M. Gong1 , X.-F. Kong1 , Z.-T. Yang2 , J. Xu2 , L. Wang2 , X.-H. Li3 , D.-H. Zhang3 , J.-H. Jiang3 , X.-X. Zhang1,2,3 . 1 Department of Infectious Diseases, 2 Chinese-French Laboratory of Life Science and Genomics, 3 Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China E-mail: [email protected] Aim: Recent genome-wide association study discovered that two polymorphisms, interferon alpha receptor 2 (IFNAR-2) F8S and interleukin 10 receptor (IL-10RB) K47E, were associated with the susceptibility of hepatitis B virus (HBV) infection in Africa. Here, we reevaluate the effects of the two polymorphisms on HBV susceptibility in the Chinese Han population, and extend to study their association with interferon response in chronic hepatitis B. Patients and Methods: We included 341 patients with chronic hepatitis B (CHB) and 341 unrelated controls presenting with asymptotic HBV selflimited infection, who were well matched in age and sex. In the CHB group, 101 patients had been treated with peg-interferon alpha-2a for 48 weeks and followed up for 24 weeks to determine the clinical response, resulting 34 individuals with sustained virologic response (SVR) and 67 individuals with non-sustained response (NR). Subgroups in the CHB