- Email: [email protected]
Polymorphisms of IL12RB2 may affect the Natural History of Primary Biliary Cirrhosis: A Single Centre Study
POSTER PRESENTATIONS Results: Twelve week treatment with vancomycin led to improvement in ALP levels (n = 20, 332+/−25 at week 0 versus 217 +/−24 mmol/L at week 12, p < 0.0001). Treatment did not result in change in Mayo risk score or TE. While ALP did not differ by genotype at baseline, after 12 weeks of treatment it was significantly lower in AA versus GG genotype patients (152+/−19 versus 281+/−33 mmol/L, p = 0.003) (Figure). Mayo risk score and TE did not differ at baseline or week 12. After vancomycin treatment, 45% patients versus 5% at baseline were VRE positive ( p = 0.008); VRE status did not differ by genotype. Conclusions: This study demonstrates the influence of a FUT2 polymorphism on response to vancomycin therapy in a cohort of patients with PSC. High levels of VRE, in combination with unclear clinical efficacy of vancomycin for PSC beyond improvement in ALP, suggest need for a longer clinical trial to determine efficacy of vancomycin in PSC cohorts with defined FUT2 genotypes.
rs6679356 CC homozygotes than TT homozygotes (128.5 ± 13.1 vs. 100.8 ± 4.8, p = 0.049). There was no significant association between studied IL12RB2 polymorphisms and liver biochemistry at the diagnosis, quality of life assessed with PBC-40 questionnaire or response to UDCA in PBC patients. Conclusions: In this first study analyzing phenotypic features of PBC carriers of the IL12RB2 polymorphisms we found that these patients are more likely to express features of liver cirrhosis at diagnosis and have significantly higher titres of antimitochondrial antibodies. Thus the presence of these SNPs may affect the natural course of primary biliary cirrhosis. It may be speculated that the assessment of these SNPs in patients who are diagnosed at the early stage of PBC could be of help in predicting subjects with a more aggressive disease course. This study was supported by the grant no. 2011/02/A/NZ5/00321 from National Science Centre in Poland.
SAT-394 POLYMORPHISMS OF IL12RB2 MAY AFFECT THE NATURAL HISTORY OF PRIMARY BILIARY CIRRHOSIS: A SINGLE CENTRE STUDY U. Wasik1, K. Kozieł1, E. Wunsch2, G.L. Norman3, P. Milkiewicz2,4, M. Milkiewicz1. 1Department of Medical Biology Laboratory; 2 Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland; 3Inova Diagnostics, Inc., San Diego, California, United States; 4Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland E-mail: [email protected]
SAT-395 IMPACT OF GENDER AND RACE/ETHNICITY ON HEPATOCELLULAR CARCINOMA, INTRAHEPATIC CHOLANGIOCARCINOMA AND EXTRAHEPATIC CHOLANGIOCARCINOMA V. Bhagat1, P. Somasundar2. 1Internal Medicine; 2Surgical Oncology, Roger Williams Medical Center, Affliated with Boston University School of Medicine, Providence, United States E-mail: [email protected]
Background and Aims: Interleukin 12 (Il-12) is a proinflammatory cytokine with immunoregulatory function. The biological effects of Il-12 is exerted through its binding to a specific receptor composed of two subunit IL-12Rβ1 and IL-12Rβ2. GWAS studies in primary biliary cirrhosis (PBC) pointed at strong associations with SNPs located within interleukin 12 receptor, beta 2 (IL12RB2) gene. The aim of the study was to find out whether genetic variation of IL12RB2 depicted with GWAS is associated with phenotypical features in PBC. Methods: Genomic DNA was isolated from blood samples of a well characterized cohort of patients with PBC (n = 306) and age and gender matched healthy volunteers (n = 258) served as a control group. Subjects included into control group were checked for the presence of AMA antibodies using M2 EP (MIT3) ELISA (QUANTA Lite®, Inova Diagnostics). Two SNPs: rs3790567, rs6679356 of IL12RB2 were genotyped using the MGB-TaqMan SNP genotyping assay.
Results: We confirmed an impact of IL12RB2 polymorphisms on PBC susceptibility (Table 1). Moreover, A allele of rs3790567 and C allele of rs6679356 were overrepresented in patients with liver cirrhosis at the diagnosis of PBC ( p = 0.002 and p = 0.01, respectively). The risk of cirrhosis at presentation increased when A allele and C allele coexisted ( p = 0.007). Unlike sp100 and gp210 autoantibodies, AMA-M2 autoantibody titres were both conspicuously higher among AA homozygotes of rs3790567 as compared with GG homozygotes (133.2 ± 10.3 vs. 102.9 ± 5.1, p = 0.02), and in
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Background and Aims: Hepatocellular (HCC) and intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangocarcinoma (ECC) are aggressive cancers that are often diagnosed late in their presentation. The purpose of this study is to investigate the impact of sex, and race/ethnicity on the incidence of HCC, ICC and ECC from 2000–2012 for individuals above the age of 65 using the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Methods: Patients diagnosed with HCC, ICC and ECC from 2000–2012 were identified from the SEER Registry. Secular trends in ageadjusted incidence by sex, and race/ethnicity were compared. Results: A total of 14,706 cases of ECC, 5,321 of ICC, 38,255 of HCC were identified from 2000–2012 using SEER database. Among all race/ethnicities and among HCC, ECC, and ICC, Asian men had the highest cancer incidence. Asian men had an incidence rate of 87.6 per 100,000/year for HCC. The incidence rates of HCC were 70, 44.4, 43.5, and 35.2 per 100,000/year for Hispanic, American Indian, Black, White males, respectively. Asian women had high incidence rates for HCC at 41.9 per 100,000/year. The incidence rates for HCC were 31.6, 24.9, 15.2, 13.4, per 100,000/year for Hispanic, American Indian, Black, White females, respectively. Asian men had the highest incidence rate of ICC at 7 per 100,000/year. The incidence rates of ICC were 5.3, 4.2, 3.2, 3.1 per 100,000/year for Hispanic, Whites, Blacks, and American Indian males, respectively. Asian females had the highest incidence rate of 5.4 per 100,000/year for ICC. The incidence rates for ICC were 5.1, 4.1, 3.3, 2.8 per 100,000/year for Hispanic, American Indian, White, Black females, respectively. Asian males have the highest incidence rate for ECC at 17.4 per 100,000/ year. The incidence rates of ECC were 16.9, 12.8, 10.8, 9.6 per 100,000/ year for Hispanic, White, Black and American Indian males, respectively. For ECC, Hispanic women have the highest incidence rate of 13 per 100,000/year. The incidence rates of ECC were 12.2, 10.2, 8.4, 7.9 per 100,000/year for Asian, American Indian, Black, White females, respectively. Conclusions: Asian men had higher incidence rates of HCC, ICC, and ECC followed by Hispanic men in the United States from 2000 to 2012. This would support interventions to educate these populations about risk factors and importance of screening for infections such as hepatitis B and C which may contribute to these cancers.
Journal of Hepatology 2016 vol. 64 | S631–S832
rs6679356 CC homozygotes than TT homozygotes (128.5 ± 13.1 vs. 100.8 ± 4.8, p = 0.049). There was no significant association between studied IL12RB2 polymorphisms and liver biochemistry at the diagnosis, quality of life assessed with PBC-40 questionnaire or response to UDCA in PBC patients. Conclusions: In this first study analyzing phenotypic features of PBC carriers of the IL12RB2 polymorphisms we found that these patients are more likely to express features of liver cirrhosis at diagnosis and have significantly higher titres of antimitochondrial antibodies. Thus the presence of these SNPs may affect the natural course of primary biliary cirrhosis. It may be speculated that the assessment of these SNPs in patients who are diagnosed at the early stage of PBC could be of help in predicting subjects with a more aggressive disease course. This study was supported by the grant no. 2011/02/A/NZ5/00321 from National Science Centre in Poland.
SAT-394 POLYMORPHISMS OF IL12RB2 MAY AFFECT THE NATURAL HISTORY OF PRIMARY BILIARY CIRRHOSIS: A SINGLE CENTRE STUDY U. Wasik1, K. Kozieł1, E. Wunsch2, G.L. Norman3, P. Milkiewicz2,4, M. Milkiewicz1. 1Department of Medical Biology Laboratory; 2 Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland; 3Inova Diagnostics, Inc., San Diego, California, United States; 4Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland E-mail: [email protected]
SAT-395 IMPACT OF GENDER AND RACE/ETHNICITY ON HEPATOCELLULAR CARCINOMA, INTRAHEPATIC CHOLANGIOCARCINOMA AND EXTRAHEPATIC CHOLANGIOCARCINOMA V. Bhagat1, P. Somasundar2. 1Internal Medicine; 2Surgical Oncology, Roger Williams Medical Center, Affliated with Boston University School of Medicine, Providence, United States E-mail: [email protected]
Background and Aims: Interleukin 12 (Il-12) is a proinflammatory cytokine with immunoregulatory function. The biological effects of Il-12 is exerted through its binding to a specific receptor composed of two subunit IL-12Rβ1 and IL-12Rβ2. GWAS studies in primary biliary cirrhosis (PBC) pointed at strong associations with SNPs located within interleukin 12 receptor, beta 2 (IL12RB2) gene. The aim of the study was to find out whether genetic variation of IL12RB2 depicted with GWAS is associated with phenotypical features in PBC. Methods: Genomic DNA was isolated from blood samples of a well characterized cohort of patients with PBC (n = 306) and age and gender matched healthy volunteers (n = 258) served as a control group. Subjects included into control group were checked for the presence of AMA antibodies using M2 EP (MIT3) ELISA (QUANTA Lite®, Inova Diagnostics). Two SNPs: rs3790567, rs6679356 of IL12RB2 were genotyped using the MGB-TaqMan SNP genotyping assay.
Results: We confirmed an impact of IL12RB2 polymorphisms on PBC susceptibility (Table 1). Moreover, A allele of rs3790567 and C allele of rs6679356 were overrepresented in patients with liver cirrhosis at the diagnosis of PBC ( p = 0.002 and p = 0.01, respectively). The risk of cirrhosis at presentation increased when A allele and C allele coexisted ( p = 0.007). Unlike sp100 and gp210 autoantibodies, AMA-M2 autoantibody titres were both conspicuously higher among AA homozygotes of rs3790567 as compared with GG homozygotes (133.2 ± 10.3 vs. 102.9 ± 5.1, p = 0.02), and in
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Background and Aims: Hepatocellular (HCC) and intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangocarcinoma (ECC) are aggressive cancers that are often diagnosed late in their presentation. The purpose of this study is to investigate the impact of sex, and race/ethnicity on the incidence of HCC, ICC and ECC from 2000–2012 for individuals above the age of 65 using the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Methods: Patients diagnosed with HCC, ICC and ECC from 2000–2012 were identified from the SEER Registry. Secular trends in ageadjusted incidence by sex, and race/ethnicity were compared. Results: A total of 14,706 cases of ECC, 5,321 of ICC, 38,255 of HCC were identified from 2000–2012 using SEER database. Among all race/ethnicities and among HCC, ECC, and ICC, Asian men had the highest cancer incidence. Asian men had an incidence rate of 87.6 per 100,000/year for HCC. The incidence rates of HCC were 70, 44.4, 43.5, and 35.2 per 100,000/year for Hispanic, American Indian, Black, White males, respectively. Asian women had high incidence rates for HCC at 41.9 per 100,000/year. The incidence rates for HCC were 31.6, 24.9, 15.2, 13.4, per 100,000/year for Hispanic, American Indian, Black, White females, respectively. Asian men had the highest incidence rate of ICC at 7 per 100,000/year. The incidence rates of ICC were 5.3, 4.2, 3.2, 3.1 per 100,000/year for Hispanic, Whites, Blacks, and American Indian males, respectively. Asian females had the highest incidence rate of 5.4 per 100,000/year for ICC. The incidence rates for ICC were 5.1, 4.1, 3.3, 2.8 per 100,000/year for Hispanic, American Indian, White, Black females, respectively. Asian males have the highest incidence rate for ECC at 17.4 per 100,000/ year. The incidence rates of ECC were 16.9, 12.8, 10.8, 9.6 per 100,000/ year for Hispanic, White, Black and American Indian males, respectively. For ECC, Hispanic women have the highest incidence rate of 13 per 100,000/year. The incidence rates of ECC were 12.2, 10.2, 8.4, 7.9 per 100,000/year for Asian, American Indian, Black, White females, respectively. Conclusions: Asian men had higher incidence rates of HCC, ICC, and ECC followed by Hispanic men in the United States from 2000 to 2012. This would support interventions to educate these populations about risk factors and importance of screening for infections such as hepatitis B and C which may contribute to these cancers.
Journal of Hepatology 2016 vol. 64 | S631–S832