H63D compound heterozygous patients

POSTER PRESENTATIONS Conclusions: This study confirms the previously reported association between rs236918 in PCSK7 and the development of cirrhosis in C282Y homozygotes but in a larger number of independent population cohorts. It also identifies a significant association between carriage of rs58542926 in TM6SF2 and the risk of developing cirrhosis in this patient population. This novel finding attests to the fact that further insight into the functional implications of carriage of this variant is clearly needed. THU-415 Inherited prothrombotic risk factors in children with extrahepatic portal vein obstruction: a case-control study M. Primignani1, I. Martinelli2, G. Tosetti1, M. Cheli3, P. Bucciarelli2, M.M. Colusso3, D. Alberti4. 1Division of Gastroenterology and Hepatology; 2A.Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca” Granda Ospedale Maggiore Policlinico, Milano, Milan; 3UOC Chirurgia Pediatrica, Ospedale Papa Giovanni XXIII, Bergamo; 4UOC Chirurgia Pediatrica, Dipartimento di Scienze Cliniche e Sperimentali, Università di Brescia, Brescia, Italy E-mail: [email protected] Background and Aims: In children extrahepatic portal vein obstruction (EHPVO) is the most frequent cause of upper gastrointestinal bleeding worldwide. Neonatal events, such as umbilical vein catheterization or omphalitis, are frequently reported as causes of obstruction. The role played by inherited thrombophilia abnormalities factor V Leiden (FVL), prothrombin G20210A mutation (PTG20210A) and antithrombin, protein C or S deficiency has not been extensively investigated yet. We investigated thrombophilia in EHPVO children, as compared with EHPVO occurring in adults (in the absence of overt neoplasia or cirrhosis) and in adult healthy controls. The two groups were compared with controls in terms of odds ratios and 95% CI. Methods: DNA analysis for the factor V Leiden and the G20210A prothrombin gene mutation and functional and/or antigenic assays for antithrombin, protein C, and protein S were carried out. Results: 53 EHPVO children, 65 EHPVO adult and 700 adult controls were included in the study. Thirty children (57%) had umbilical vein catheterization. FVL and PTG20210A were found in 3 (6%) and one (2%) children and in 2 (3%) and 14 (22%) adults, respectively, for an OR of 2.4 (95% CI 0.7–8.5) for FVL and 0.6 (95% CI 0.1–4.2) for PTG20210A in children, and of 0.8 (95% CI 0.1–6.4) for FVL and 8.1 (95% CI 3.8– 17.5) in adults. 53% of children and 28% of EHPVO adult had one or more deficiency of antithrombin, protein C or S but the inheritance of such deficiencies could be excluded in all children and in 14 of 18 adults. Primary myeloproliferative disorders were excluded in all children, but were the most common cause of EHPVO in adults, occurring in 35% of them. One only risk factor for EHPVO was identified in 57% children and 40% adults. Two or more risk factors were recognized in 15% children and 37% adults EHPVO (c2 = 7.14, p = 0.028), whereas no risk factors were identified in 28% of children and 23% adults EHPVO. Conclusions: In children, umbilical vein catheterization is the most common cause of EHPVO. Differently from adults with EHPVO, who have a significantly increased rate of PTG20210A, inherited thrombophilia has no role in EHPVO children. The occurrence of multiple risk factors is significantly lower in paediatric as compared to adult EHPVO. Up to 30% of paediatric EHPVO occur in the absence of any recognized risk factor. THU-416 Association between GNPAT genotypes and serum iron parameters in C282Y homozygous and C282Y/H63D compound heterozygous patients M. Tobiasch1, H. Zoller1, A. Finkenstedt1, H. Tilg1. 1Universitätskliniken LKH Innsbruck, Innsbruck, Austria E-mail: [email protected]

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Background and Aims: The GNPAT D519G genotype (rs11558492) has been associated with severe iron overload in a small cohort of patients with C282Y homozygous hemochromatosis. Subsequent studies in larger cohorts showed a higher frequency of the GNPAT G allele in hemochromatosis patients, but no association with serum iron parameters. The aim of this study was to assess the frequency and the effect of the GNPAT genotype on serum iron parameters in a large cohort of C282Y homozygous and C282Y/H63D compound heterozygous patients. Methods: The GNPAT variant rs11558492 in patients with C282Y homozygosity and C282Y/H63D compound heterozygosity was assessed using a TaqMan SNP genotyping assay (Thermo Fisher Scientific, Waltham, MA). Serum iron parameters were compared between the GNPAT variants. Studies on GNPAT in hemochromatosis were additionally screened for allele frequencies, and included in a risk meta-analysis. Results: The GNPAT genotype was assessed in 348 patients (231 males, median age 49 years). GNPAT heterozygote and homozygote variants were more frequent in C282Y/H63D compound heterozygotes (37% and 7%) as compared to C282Y homozygote patients (33% and 2%). This difference did not reach statistical significance ( p, 0.06). Median serum ferritin concentration and transferrin saturation were highest in GNPAT wild types (678 μg/l and 79%), intermediate in GNPAT heterozygotes (578 μg/l and 70%), and lowest in GNPAT homozygotes (477 μg/l and 54%). The difference was statistically significant for transferrin saturation in the overall cohort ( p, 0.001), in the C282Y/H63D compound heterozygote subgroup ( p, 0.020), and for ferritin in C282Y homozygotes ( p, 0.048). Results were comparable when the calculation was restricted to male patients with a ferritin level above the 3rd quartile, without reaching statistical significance. The association between serum iron parameters and GNPAT genotype appeared to be sex dependent as the effect was seen in male but not in female patients. In published cohorts, the frequency of the GNPAT G allele is, in tendency, increased in the HFE cohorts as compared to controls. However, the frequency of the GNPAT G allele in our sample was not increased as compared to population databases (21% in all patients, 18% in C282Y homozygotes). Conclusions: Serum iron parameters differed significantly between GNPAT genotypes in C282Y homozygous und C282Y/H63 compound heterozygote patients. In contrast to previous studies, GNPAT GG genotype was associated with less severe iron overload. THU-417 Antibiotics induce remission in pediatric PSC-AIH overlap syndrome allowing corticosteroid-free therapy P. Sambon1, S. Varma1, M. Komuta2, P. Clapuyt3, E. Sokal1. 1Service de Gastro-entérologie et Hépatologie Pédiatrique; 2Service of Anatomical Pathology; 3Pediatric Radiology Unit, Université catholique de Louvain, cliniques universitaires Saint Luc, Brussels, Belgium E-mail: [email protected] Background and Aims: Concomitant presence of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) is labelled as AIH-PSC overlap syndrome or autoimmune sclerosing cholangitis (ASC). Treatment of AIH with corticosteroids and azathioprine; and of the PSC component with ursodeoxycholic acid (UDCA) is the standard practice. Antibiotics are increasingly being shown to have benefit in PSC but their role in paediatric ASC is not well evaluated. We investigated the response to oral antibiotics as initial or subsequent therapy in children with ASC. Methods: Patients diagnosed with ASC on basis of biochemical, liver biopsy and radiology findings were included. They received metronidazole or vancomycin for 14 days [10–220] either at diagnosis (i.e. initial therapy) or during their maintenance period. When antibiotics were administered as initial therapy, steroid free induction regime was adopted. In children during the

Journal of Hepatology 2017 vol. 66 | S95–S332