- Email: [email protected]
467 DOWNREGULATION OF NK CELL PHENOTYPE AND FUNCTION IN HBV PATIENTS TREATED WITH ENTECAVIR
POSTERS using one way ANOVA unequal variance (Welch) test with multiple testing correction by Benjamini-Hochberg test. Patients were followed at least 12 months and diagnosed according to the EB KEEFFE 2008 guideline. Results: A distinct expression pattern among different inflammatory status existed, both in G scoring and ALT levels. CXCR3 ligands (CXCL9, 10, 11) were significantly up-regulated (with a fold change ≥3) in the liver tissue of patients with Scheuer score of G4 compared to G0 Similar results were obtained from different ALT groups, with the same three ligands significantly up-regulated in patients with 2–5 times normal ALT compared to normal. Furthermore, they remained to be the only three upregulated genes in patients with ALT level higher than 5 times normal. Conclusions: This study was performed on human liver specimens to elucidate the different gene expression patterns in HBV patients with follow-up data, and results suggested that CXCR3 ligands were most involved in the high inflammatory status and fibrosis of HBV treatment naïve patients. Follow-up data will be used to confirm its prediction role in the prognosis. 465 INTRAHEPATIC HEPATITIS B VIRAL DNA AND CCCDNA IN TUMOR VS. NON-NEOPLASTIC LIVER OF PATIENTS WITH HBV AND HCC Q. Wang1 , W. Luan1 , M.I. Fiel2 , S. Blank1 , K.W. Kim1 , S.P. Hiotis1 . 1 Surgery, 2 Pathology, Mount Sinai School of Medicine, New York, NY, USA E-mail: [email protected] Background: Covalently closed circular HBV DNA (cccDNA) accumulates as a stable mini chromosome in the nuclei of infected hepatocytes and is essential for HBV replication. Persistent viral infection likely plays an important role in HCC initiation, and progression; however, understanding of viral regulation in HCC patients is limited. This study aims to compare intrahepatic total HBV DNA and cccDNA levels in paired HCC and non-neoplastic liver tissues of HBV HCC patients. Methods: 108 prospective patients who underwent liver resection for HBV-HCC at Mount Sinai Hospital in New York, NY between 2008 and 2011 were included. Patients consisted of a broad chronic HBV cohort, many of whom had been started on antiviral therapy prior to the diagnosis of HCC. Total intrahepatic HBV DNA, cccDNA, and albumin (housekeeping gene) were measured from paired HCC and non-neoplastic liver tissue by real-time quantitative PCR. Circulating HBV DNA was determined by standard pre-operative clinical blood work. Results: 102 of the 108 patients (94%) had detectable total HBV DNA and cccDNA in the non-neoplastic liver tissues, while significantly fewer had detectable HBV DNA and cccDNA in paired HCC tissues (80% and 54%, p = 0.002 and p = 0.0001, respectively). The median HBV DNA copy per hepatocyte measured 0.049 in non-neoplastic liver and 0.0057 in HCC (p = 0.2). The cccDNA copy per hepatocyte in non-neoplastic liver was significantly greater than in HCC (median 0.0044 vs. 0.000004, p < 0.0001). The proportion of cccDNA in total HBV DNA in non-neoplastic liver was also significantly higher than in HCC (9.8% vs. 0.5%, p < 0.0001). Only 37% had detectable circulating HBV DNA in blood. Interestingly, circulating HBV DNA correlated significantly with HBV DNA and cccDNA in non-neoplastic liver (p = 0.005 and p = 0.006, respectively), but not in HCC (p = 0.6 and p = 1.0, respectively). Conclusions: Most patients had detectable intrahepatic HBV DNA, and viral load in the blood did not accurately reflect viral burden in the liver of HBV-HCC patients. The significantly lower level and proportion of HBV cccDNA in tumor compared to that in paired non-neoplastic liver tissue suggest that different mechanisms likely control the pool size of cccDNA and HBV DNA in these two tissue compartments. S184
466 SERUM IP-10 IN THE NATURAL COURSE OF HBEAG(−) PERSISTENT HBV-INFECTION J. Jaroszewicz, M. Luto, A. Parfieniuk-Kowerda, M. Plonska-Rogalska, T.W. Lapinski, R. Flisiak. Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland E-mail: [email protected] Background: Interferon gamma-induced protein-10 (IP-10) is secreted by variety of immune cells in response to IFN-gamma. Serum IP-10 measurement has an already well-established role in prediction of therapy response in chronic hepatitis C. Its role in HBV-infection is less clear. Recently we have shown that IP-10 levels were associated with HBsAg-loss during long-term therapy with nucleoside/nucleotide analogues. The aim of this study was to investigate correlates of IP-10 and phase of infection in a prospective cohort of HBeAg(−) patients not receiving anti-HBV therapies. Methods: Overall serum IP-10 was measured in 119 HBeAg(−) HBVinfected patients (65 male, mean age 42) by ELISA (R&D Systems). Results obtained in a prospective cohort of 80 patients with normal ALT (N-ALT) activity (followed for 12–15 months) were compared with 39 patients with HBeAg(−) hepatitis with elevated ALT (E-ALT) and 30 healthy individuals. Results: Among 80 patients with N-ALT followed at tri-monthly basis only 18 (22.5%) remained low replicative (LR, HBV-DNA <2000 IU/mL) thorough the follow-up, while remaining 62 patients showed HBV-DNA fluctuations (RE group) up to 6.2log 10 IU/mL and in 4 (5%) additional enzymatic flares were observed. Baseline mean IP-10 levels were highest in patients with E-ALT (396.7 pg/mL), while lower in in N-ALT (228.2 pg/mL, P < 0.005) and healthy individuals (195.8± pg/mL, P = 0.01). In overall cohort serum IP10 correlated positively with ALT activity (r = 0.28, P < 0.01) and age (r = 0.21, P = 0.03), while an association with HBV-DNA was not significant. In patients with N-ALT IP-10 levels no longer correlated with ALT. Furthermore, IP-10 levels were comparable in LR (230.8 pg/mL) and RE subjects (231.8 pg/mL). Serum IP-10 levels exceeded these observed in a control group (<200 pg/mL) were noted in 50% of LR, 59% of RE and 62% of ENH-patients. No cases of spontaneous HBsAg-loss were so far observed in this cohort. Conclusion: The activation of endogenous interferon-gamma system, as reflected by serum IP-10 levels seems to be associated with the phase of HBV-infection and highest in patients with active inflammatory processes. The potential usefulness of serum IP-10 in the natural course of HBV-infection should be further evaluated in long-term cohorts with cases of HBsAg-loss. 467 DOWNREGULATION OF NK CELL PHENOTYPE AND FUNCTION IN HBV PATIENTS TREATED WITH ENTECAVIR X. Sun, P. Zhao, J. Tai, J. Feng, J. Niu, Y. Jiang. First Hospital, Jilin University, Changchun, China E-mail: [email protected] Background: During the early phase of hepatitis B virus (HBV) infection, the activation of NK cells seems to be an important factor determining the subsequent induction of adaptive immunity and ultimately the outcome of HBV infection. This study aimed to investigate phenotype and function of NK cells in patients with chronic HBV infection and to study the effect of entecavir therapy. Methods: Peripheral blood NK cells from 18 chronic HBV patients were compared to NK cells of 14 healthy controls. The effect of entecavir therapy on the phenotype and function of NK cells in patients with chronic HBV infection were characterized by flow cytometry analysis. Their serum alanine aminotranferease (ALT) and aspartate aminotransferase (AST) concentrations, and HBV viral
Journal of Hepatology 2012 vol. 56 | S71–S224
POSTERS loads were measured. The potential association of the frequency of peripheral NK cells sbuset with clinical measures was analyzed. Results: Characterization of NK cells subsets revealed that CD3CD56+ NK cells were significant reduced in HBV patients compared to healthy control. No significant difference about the percentages of NK cells was found after entecavir treatment. Furthermore, we analyzed NK cell receptor expression in the two groups of individuals and included natural activation receptors and inhibitory receptors. Interestingly, We found the percentages of activation receptors CD3-CD56+NKG2D+ and CD3-CD56+NKP30+ NK cells in HBV patients which were significantly higher than healthy individuals were down-regulated after entecavir treatment. However, there was no significant changed about the expression of inhibitory receptors was found after entecavir treatment. Spearman’s correlation analysis revealed that the percentage of NKG2D+ and NKP30+ NK cells was significantly positively correlated with the serumALT in HBV patients. Characterization of NK cell degranulation indicated that the frequency of CD107a+ NK cells in patients with HBV, in response to K562 stimulation, which was significantly higher than that in healthy controls was decreased in patients after entecavir treatment. Conclusions: These data examined that after entecavir treatment of HBeAb-positive chronic HBV patients in China not only leads to the reduction of HBV DNA load and normalization of ALT and AST but also can recovery the NK cell-mediated immunity in chronic HBV patients. 468 HEPATITIS B SURFACE ANTIGEN EXPRESSION IS ASSOCIATED WITH EARLY RECURRENCE IN EARLY STAGE HEPATOCELLULAR CARCINOMA J. Jin, H.Y. Jung, J.J. Jang, K.B. Lee. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: B viral hepatitis is one of the main risk factors for hepatocellular carcinomas (HCC) in Korea. Hepatocellular carcinogenesis by virus may be by direct oncogenic effects of viral proteins and chronic liver injury inducing accumulated genetic mutation during reparative cellular regeneration. Hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infected tissues represent the replicative status of infected virus. We aim to study the relationship between the status of replicative viral particle in HCC proper and clinicopathologic features. Methods: We assessed the expression status of HBsAg and HBcAg by immunohistochemistry in 448 HCCs blocked in 13 tissue microarrays and evaluated clinicopathologic features and survival rates depending on HBsAg and HBcAg expression. Results: Positive rates of HBsAg in cytoplasm and HBcAg in nuclei were 6.9% (31/448) and 10.5% (47/448) and 9 patients showed positivity both HBsAg and HBcAg (2% of 448 patients). Underlying causes of hepatitis for 31 HBsAg positive patients were 26 HBV (8.2% of 314 HBVs), 1 HBV and HCV coinfection, 2 nonB-nonC hepatitis and 2 unknown. Those for HBcAg positive patients were 38 HBV (12.1% of 314 HBVs), 1 HCV, 1 HBV and HCV coinfection and 4 nonB-nonC hepatitis and 3 unknown. HBsAg expressing HCCs showed lower Edmonson-Steiner nuclear grade, lower pT stage, limited tumor extent, lower serum a-fetoprotein level, and advanced fibrosis stage than HBsAg negative HCCs. (all p values <0.05 by chi square test or Mann-Whitney test). HBcAg positive HCCs revealed similar clinicopathologic features except for fibrosis stage. Early tumor recurrence rate within 2 years in pT1–1 stage of HBsAg positive patients was higher than of HBsAg negative patients (50.0% (12/24) vs 39.3% (125/318), p = 0.048). Conclusion: HBsAg or HBcAg expressing HCCs had relatively differentiated histologic features and early clinical stage but tend to early recur within two years in early stage HCC patients.
469 GENETIC MAPPING QUANTITATIVE TRAIT LOCI FOR HOST CONTROL OF HBV VIRAL LOAD IN THE HLA REGION AMONG FAMILIES OF HEPATOCELLULAR CARCINOMA W.-Y. Kao1 , S.-Y. Chou1 , J.-W. Jian1 , P.-J. Chen2 , C.-L. Lin3 , C.-J. Liu2 , Y.-F. Liaw4 , S.-M. Lin4 , S.-D. Lee5 , M.-W. Yu1 . 1 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 2 Department of Internal Medicine, Division of Gastroenterology, National Taiwan University Hospital, National Taiwan University College of Medicine, 3 Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, 4 Liver Research Unit, Chang Gung University, Taoyuan, 5 Department of Medicine, Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan R.O.C. E-mail: [email protected] Background and Aims: Family history is an important risk factor for hepatocellular carcinoma (HCC). The cause for familial aggregation of HCC remains unclear, but genetic factors that influence immune response might confer susceptibility. We have previously shown that heritability accounts for approximately 30% of the total variation in HBV viral load for families of HCC. Many genes in HLA region encode proteins critical in activating immune response to viral infection. We aimed to use linkage disequilibrium mapping, which provides a powerful method for fine-structure localization of rare disease genes, to identify a quantitative trait locus (QTL) for host control of HBV viral load in HLA region with a large collection of families with HCC. Methods: The family sample consisted of 826 HBsAg-positive subjects (465 men and 361 women) from 304 different families; each was ascertained through a single HBsAg-positive index patient with HCC. We performed family-based association analysis by using the quantitative transmission disequilibrium test with a dense map of microsatellite markers across the HLA region on chromosome 6p21.3 spanning ~3.6 Mb of DNA. These analyses were performed using age, sex, HBV genotype, and serum ALT as covariates. Results: Twenty-four percent of families were infected with genotype C HBV, 61% were infected with genotype B HBV, and the remaining families had discordant HBV genotypes between relatives. HBeAg was present in 98 (12.0%) subjects, and elevated serum ALT levels were found in 186 (28.1%) subjects. We mapped the QTL for control of HBV viremia levels to a region spanning 1.1 Mb within the HLA class I region. Three microsatellite markers in this critical segment displayed significant association, and one marker reached highly significant p-value (p = 0.0008, Bonferronicorrected p = 0.0275). Investigation of recombinant haplotypes in the identified segment revealed the presence of two haplotypes. Notably, a rare homozygous haplotype was associated with an increase in viral load of ~2 log. Conclusions: The results of this study indicate that HLA class I polymorphisms may determine host control of HBV viral load, suggesting genetic variation in T cell responses can influence the nature of chronic HBV infection in families of HCC. 470 PHYLOGENETIC ANALYSES OF HBV PRE-S/S GENES IN MOTHER-CHILD PAIRS WITH LONG-TERM INFECTION BY PRESUMED VERTICAL TRANSMISSION H.S. Kim, J.W. Park, S.R. Shin, K.T. Suk, M.K. Jang, S.H. Park, D.J. Kim, M.S. Lee, C.K. Park. Department of Internal Medicine, Hallym University Medical Center, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: Vertical transmission from mother to child is considered the main route of chronic hepatitis B virus (HBV) infection in Far East Asia, which is an important predictor for the response to antiviral therapies or complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is very important to
Journal of Hepatology 2012 vol. 56 | S71–S224
S185
466 SERUM IP-10 IN THE NATURAL COURSE OF HBEAG(−) PERSISTENT HBV-INFECTION J. Jaroszewicz, M. Luto, A. Parfieniuk-Kowerda, M. Plonska-Rogalska, T.W. Lapinski, R. Flisiak. Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland E-mail: [email protected] Background: Interferon gamma-induced protein-10 (IP-10) is secreted by variety of immune cells in response to IFN-gamma. Serum IP-10 measurement has an already well-established role in prediction of therapy response in chronic hepatitis C. Its role in HBV-infection is less clear. Recently we have shown that IP-10 levels were associated with HBsAg-loss during long-term therapy with nucleoside/nucleotide analogues. The aim of this study was to investigate correlates of IP-10 and phase of infection in a prospective cohort of HBeAg(−) patients not receiving anti-HBV therapies. Methods: Overall serum IP-10 was measured in 119 HBeAg(−) HBVinfected patients (65 male, mean age 42) by ELISA (R&D Systems). Results obtained in a prospective cohort of 80 patients with normal ALT (N-ALT) activity (followed for 12–15 months) were compared with 39 patients with HBeAg(−) hepatitis with elevated ALT (E-ALT) and 30 healthy individuals. Results: Among 80 patients with N-ALT followed at tri-monthly basis only 18 (22.5%) remained low replicative (LR, HBV-DNA <2000 IU/mL) thorough the follow-up, while remaining 62 patients showed HBV-DNA fluctuations (RE group) up to 6.2log 10 IU/mL and in 4 (5%) additional enzymatic flares were observed. Baseline mean IP-10 levels were highest in patients with E-ALT (396.7 pg/mL), while lower in in N-ALT (228.2 pg/mL, P < 0.005) and healthy individuals (195.8± pg/mL, P = 0.01). In overall cohort serum IP10 correlated positively with ALT activity (r = 0.28, P < 0.01) and age (r = 0.21, P = 0.03), while an association with HBV-DNA was not significant. In patients with N-ALT IP-10 levels no longer correlated with ALT. Furthermore, IP-10 levels were comparable in LR (230.8 pg/mL) and RE subjects (231.8 pg/mL). Serum IP-10 levels exceeded these observed in a control group (<200 pg/mL) were noted in 50% of LR, 59% of RE and 62% of ENH-patients. No cases of spontaneous HBsAg-loss were so far observed in this cohort. Conclusion: The activation of endogenous interferon-gamma system, as reflected by serum IP-10 levels seems to be associated with the phase of HBV-infection and highest in patients with active inflammatory processes. The potential usefulness of serum IP-10 in the natural course of HBV-infection should be further evaluated in long-term cohorts with cases of HBsAg-loss. 467 DOWNREGULATION OF NK CELL PHENOTYPE AND FUNCTION IN HBV PATIENTS TREATED WITH ENTECAVIR X. Sun, P. Zhao, J. Tai, J. Feng, J. Niu, Y. Jiang. First Hospital, Jilin University, Changchun, China E-mail: [email protected] Background: During the early phase of hepatitis B virus (HBV) infection, the activation of NK cells seems to be an important factor determining the subsequent induction of adaptive immunity and ultimately the outcome of HBV infection. This study aimed to investigate phenotype and function of NK cells in patients with chronic HBV infection and to study the effect of entecavir therapy. Methods: Peripheral blood NK cells from 18 chronic HBV patients were compared to NK cells of 14 healthy controls. The effect of entecavir therapy on the phenotype and function of NK cells in patients with chronic HBV infection were characterized by flow cytometry analysis. Their serum alanine aminotranferease (ALT) and aspartate aminotransferase (AST) concentrations, and HBV viral
Journal of Hepatology 2012 vol. 56 | S71–S224
POSTERS loads were measured. The potential association of the frequency of peripheral NK cells sbuset with clinical measures was analyzed. Results: Characterization of NK cells subsets revealed that CD3CD56+ NK cells were significant reduced in HBV patients compared to healthy control. No significant difference about the percentages of NK cells was found after entecavir treatment. Furthermore, we analyzed NK cell receptor expression in the two groups of individuals and included natural activation receptors and inhibitory receptors. Interestingly, We found the percentages of activation receptors CD3-CD56+NKG2D+ and CD3-CD56+NKP30+ NK cells in HBV patients which were significantly higher than healthy individuals were down-regulated after entecavir treatment. However, there was no significant changed about the expression of inhibitory receptors was found after entecavir treatment. Spearman’s correlation analysis revealed that the percentage of NKG2D+ and NKP30+ NK cells was significantly positively correlated with the serumALT in HBV patients. Characterization of NK cell degranulation indicated that the frequency of CD107a+ NK cells in patients with HBV, in response to K562 stimulation, which was significantly higher than that in healthy controls was decreased in patients after entecavir treatment. Conclusions: These data examined that after entecavir treatment of HBeAb-positive chronic HBV patients in China not only leads to the reduction of HBV DNA load and normalization of ALT and AST but also can recovery the NK cell-mediated immunity in chronic HBV patients. 468 HEPATITIS B SURFACE ANTIGEN EXPRESSION IS ASSOCIATED WITH EARLY RECURRENCE IN EARLY STAGE HEPATOCELLULAR CARCINOMA J. Jin, H.Y. Jung, J.J. Jang, K.B. Lee. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: B viral hepatitis is one of the main risk factors for hepatocellular carcinomas (HCC) in Korea. Hepatocellular carcinogenesis by virus may be by direct oncogenic effects of viral proteins and chronic liver injury inducing accumulated genetic mutation during reparative cellular regeneration. Hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infected tissues represent the replicative status of infected virus. We aim to study the relationship between the status of replicative viral particle in HCC proper and clinicopathologic features. Methods: We assessed the expression status of HBsAg and HBcAg by immunohistochemistry in 448 HCCs blocked in 13 tissue microarrays and evaluated clinicopathologic features and survival rates depending on HBsAg and HBcAg expression. Results: Positive rates of HBsAg in cytoplasm and HBcAg in nuclei were 6.9% (31/448) and 10.5% (47/448) and 9 patients showed positivity both HBsAg and HBcAg (2% of 448 patients). Underlying causes of hepatitis for 31 HBsAg positive patients were 26 HBV (8.2% of 314 HBVs), 1 HBV and HCV coinfection, 2 nonB-nonC hepatitis and 2 unknown. Those for HBcAg positive patients were 38 HBV (12.1% of 314 HBVs), 1 HCV, 1 HBV and HCV coinfection and 4 nonB-nonC hepatitis and 3 unknown. HBsAg expressing HCCs showed lower Edmonson-Steiner nuclear grade, lower pT stage, limited tumor extent, lower serum a-fetoprotein level, and advanced fibrosis stage than HBsAg negative HCCs. (all p values <0.05 by chi square test or Mann-Whitney test). HBcAg positive HCCs revealed similar clinicopathologic features except for fibrosis stage. Early tumor recurrence rate within 2 years in pT1–1 stage of HBsAg positive patients was higher than of HBsAg negative patients (50.0% (12/24) vs 39.3% (125/318), p = 0.048). Conclusion: HBsAg or HBcAg expressing HCCs had relatively differentiated histologic features and early clinical stage but tend to early recur within two years in early stage HCC patients.
469 GENETIC MAPPING QUANTITATIVE TRAIT LOCI FOR HOST CONTROL OF HBV VIRAL LOAD IN THE HLA REGION AMONG FAMILIES OF HEPATOCELLULAR CARCINOMA W.-Y. Kao1 , S.-Y. Chou1 , J.-W. Jian1 , P.-J. Chen2 , C.-L. Lin3 , C.-J. Liu2 , Y.-F. Liaw4 , S.-M. Lin4 , S.-D. Lee5 , M.-W. Yu1 . 1 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 2 Department of Internal Medicine, Division of Gastroenterology, National Taiwan University Hospital, National Taiwan University College of Medicine, 3 Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, 4 Liver Research Unit, Chang Gung University, Taoyuan, 5 Department of Medicine, Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan R.O.C. E-mail: [email protected] Background and Aims: Family history is an important risk factor for hepatocellular carcinoma (HCC). The cause for familial aggregation of HCC remains unclear, but genetic factors that influence immune response might confer susceptibility. We have previously shown that heritability accounts for approximately 30% of the total variation in HBV viral load for families of HCC. Many genes in HLA region encode proteins critical in activating immune response to viral infection. We aimed to use linkage disequilibrium mapping, which provides a powerful method for fine-structure localization of rare disease genes, to identify a quantitative trait locus (QTL) for host control of HBV viral load in HLA region with a large collection of families with HCC. Methods: The family sample consisted of 826 HBsAg-positive subjects (465 men and 361 women) from 304 different families; each was ascertained through a single HBsAg-positive index patient with HCC. We performed family-based association analysis by using the quantitative transmission disequilibrium test with a dense map of microsatellite markers across the HLA region on chromosome 6p21.3 spanning ~3.6 Mb of DNA. These analyses were performed using age, sex, HBV genotype, and serum ALT as covariates. Results: Twenty-four percent of families were infected with genotype C HBV, 61% were infected with genotype B HBV, and the remaining families had discordant HBV genotypes between relatives. HBeAg was present in 98 (12.0%) subjects, and elevated serum ALT levels were found in 186 (28.1%) subjects. We mapped the QTL for control of HBV viremia levels to a region spanning 1.1 Mb within the HLA class I region. Three microsatellite markers in this critical segment displayed significant association, and one marker reached highly significant p-value (p = 0.0008, Bonferronicorrected p = 0.0275). Investigation of recombinant haplotypes in the identified segment revealed the presence of two haplotypes. Notably, a rare homozygous haplotype was associated with an increase in viral load of ~2 log. Conclusions: The results of this study indicate that HLA class I polymorphisms may determine host control of HBV viral load, suggesting genetic variation in T cell responses can influence the nature of chronic HBV infection in families of HCC. 470 PHYLOGENETIC ANALYSES OF HBV PRE-S/S GENES IN MOTHER-CHILD PAIRS WITH LONG-TERM INFECTION BY PRESUMED VERTICAL TRANSMISSION H.S. Kim, J.W. Park, S.R. Shin, K.T. Suk, M.K. Jang, S.H. Park, D.J. Kim, M.S. Lee, C.K. Park. Department of Internal Medicine, Hallym University Medical Center, Seoul, Republic of Korea E-mail: [email protected] Background and Aims: Vertical transmission from mother to child is considered the main route of chronic hepatitis B virus (HBV) infection in Far East Asia, which is an important predictor for the response to antiviral therapies or complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is very important to
Journal of Hepatology 2012 vol. 56 | S71–S224
S185