POSTERS
891
PIVOT ROLE OF PAI 1 4G4G IN NON-CIRRHOTIC PORTAL VEIN THROMBOSIS AND BUDD-CHIARI SYNDROME
M. D’Amico1, M. Niceta2, P. Sammarco2, R. Virdone3, E. Sinagra1.
1Gastroenterology Unit, V. Cervello Hospital, Palermo, Italy;2Genetics,
V. Cervello Hospital, Palermo, Italy;3Internal Medicine, V. Cervello Hospital, Palermo, Italy, Palermo, Italy
E-mail: mario.dami@libero.it
Background and Aim:Thrombophilic genetic factors (TGFs) have been shown to be a risk factor for deep venous thrombosis in different districts. We showed recently that PAI1 4G4G and MTHFR C677 TT were significantly more frequent both in hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT) in patients with liver cirrhosis. The aim of our study was to evaluate PAI1 4G4G, MTHFR C677 TT, V Leiden Q506, and prothrombin G20210A, as risk factors for PVT or Budd-Chiari Syndrome (BCS) in patients without liver cirrhosis or HCC.
Materials and methods:53 patients with PVT of which 20 with chronic myeloproliferative diseases (CMPD), 32 BCS of which 17 with CMPD, 96 patients with CMPD without PVT or BCS and 94 PLT donors healthy controls (HC) were consecutively enrolled. The TGFs studied were analysed in relation to the presence of PVT or BCS. After univariate analysis, we selected each significant TGF as independent variable, to perform multivariate logistic regression analysis using PVT, BCS and CMPD as dependent variable anyone of which significantly related to one or more TGFs.
Results:We found that PAI 1 4G4G homozygosis and the presence of more than one TGF were significantly (p<0.005) more frequent in patients with PVT and BCS vs HC. MTHFR C677 TT homozygosis was significant different (p<0.005) in PVT group vs HC and V Leiden Q506 was significant (p<0.005) in BCS vs HC. The synthesis of 3 logistic regression analysis for any disease studied showed the significant (p<0.05) value of: PAI1 4G4G in PVT, BCS and CMPD, MTHFR 677TT in PVT and V Leiden Q506 in BCS.
Conclusion:Our results show for the first time that PAI1 4G4G plays a significant role in PVT and BCS. The role of MTHFR 677TT was confirmed in PVT even without chronic liver diseases. We hypothesize that the significant relation of PAI1 4G4G with CMPD may indicate a potential pathogenetic role of this factor through microvascular thrombosis and fibrogenesis; this relation could also be an explanation of frequent thrombotic events in CMPD.
892
URSODEOXYCHOLIC ACID (UDCA) IN THE TREATMENT OF INTRAHEPATIC CHOLESTASIS OF PREGNANCY (ICP): A SYSTEMATIC REVIEW AND META-ANALYSES WITH SPECIFIC ASSESSMENT OF FETAL OUTCOME
V. Di Martino1, L. Sentilhes2, H.M. Reyes3, A. Glantz4,
J. Kondrackiene5, T. Binder6, P.L. Nicastri7, A. Locatelli8, A. Floreani9, I. Hernandez3, Y. Bacq10.1Service d’H´epatologie, Universit´e de Franche Comt´e, CHU Jean Minjoz, Besan ¸con,2Service de Gyn´ecologie-Obst´etrique, Angers, France;3Department of Experimental Medicine, Universidad del Chile, Santiago, Chile;4Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Goteborg, Sweden; 5Department of Gastroenterology, Kaunas University of Medicine,
Konas, Lithuania;6Department of Obstetrics and Gynecology, Medical School Charles Univ, Prague, Czech Republic;7Divisione di Ostetrica e Ginecologia, Universita di Bari, Bari,8Divisione di Ostetrica e Ginecologia, ISBM San Gerardo, Monza,9Department of Gastroenterology, Universita di Padova, Padova, Italy;10Service d’H´epato-Gastroenterologie, CHU de Tours, Tours, France
E-mail: vdimartino@chu-besancon.fr
ICP is characterized by pruritus associated with elevated serum bile acid and serum ALT levels, and may increase the risk of prematurity and intrauterine fetal death (IUFD). UDCA is the best medical treatment for ICP but its role for preventing adverse fetal outcome
remains to be demonstrated. To address this point, we performed a meta-analysis of randomized clinical trials (RCTs) comparing UDCA to control treatments (CT) or placebo.
Methods: A compilation of the 9 RCTs (427 patients) comparing UDCA (n = 207) to CT (n = 227 including 70 placebo, 36 dexamethasone, 65 SAM, 42 cholestyramin) reported on the litterature have been achieved. 8 endpoints were studied: (1) improvement of pruritus, (2) normalization of ALT within 14 to 21 days of treatment, (3) >50% decrease of total bile acids (TBA), (4) total prematurity (TP: spontaneous or induced delivery<37 wks gestation), (5) spontaneous prematurity, (6) fetal distress (FD), (7) neonatal respiratory distress syndrome (RDS), and (8) stay in neonatal ICU. The small number of recorded IUFD (only 2 in the CT group) did not allow specific analysis on this point. For each endpoint, we performed pooled analyses comparing UDCA vs. CT and pooled analyses comparing UDCA vs. placebo. To homogenise the definitions among different RCTs, feedback was elicited from each coordinator of the published RCTs by sending them a standardized questionnaire including 35 queries. The statistical analysis used the method of Der Simonian and Laird. Results:Pooled analyses showed that UDCA vs CT was associated with improvement of pruritus (OR: 4.91; 95% CI: 2.17–11.09, p<0.001), decrease in TBA (OR: 4.57; 1.86–11.25, p<0.001), more frequent ALT normalization (OR: 3.73; 1.74–8.00, p<0.001), less frequent TP (OR: 2.72; 1.33–5.55, p<0.001), FD (OR: 2.10; 1.13–3.87, p<0.01), RDS (OR: 2.98; 1.18–7.49, p = 0.02), and hospitalisations in neonatal ICU (OR: 2.01; 1.01–4.01, p = 0.049). Compared to placebo, UDCA improved pruritus (OR: 4.73; 1.61–13.89, p = 0.0016), serum ALT (OR: 5.90; 1.93–18.07, p<0.001), and TBA (OR: 3.37; 1.44–7.90, p<0.01).
Conclusion: This meta-analysis confirms that UDCA is more efficacious than CT for improving pruritus, serum ALT and TBA in women with ICP, and supports its benefit on fetal outcome. The use of UDCA may also decrease the rate of induced prematurity.
893
IRON-DEPENDENT REGULATION OF HEPATIC HEPCIDIN EXPRESSION IN HJV−/−MICE
K. Gkouvatsos, K. Pantopoulos.Lady Davis for Medical Research and Department of Medicine, McGill University, Montreal, QC, Canada
E-mail: konstantinos.gkouvatsos@mail.mcgill.ca
Background and Aims:Hemojuvelin (HJV) is a bone morphogenetic protein (BMP) co-receptor that plays a pivotal role in systemic iron homeostasis. Mutations in HJV are causatively linked to juvenile hemochromatosis, an early onset and severe form of hereditary iron overload. The marked suppression of hepcidin expression observed in juvenile hemochromatosis patients and in HJV −/− mice, suggests a function of hemojuvelin, as an upstream regulator of this liver-derived iron-regulatory peptide hormone. To elucidate the role of HJV in iron-sensing pathways, we employed HJV −/− mice and analyzed their responses to dietary iron manipulations.
Methods:8-weeks old HJV −/− and HJV +/+ control mice were placed in diets of varying iron content (low, normal and high) for 4 weeks. Additionally, a fourth group of mice was subjected to acute iron overload by intraperitoneal injection of iron dextran. Serum iron parameters, liver iron deposition and hepatic hepcidin, pSmad1/5/8 and BMP6 expression were assessed.
Results:Serum iron levels were significantly increased in HJV −/− mice in comparison to wild type controls in all diet regimens. Interestingly, transferrin was highly saturated (97%) in HJV −/− mice regardless the iron content of the diet. Massive liver iron deposition in HJV −/− mice was assessed with both a qualitative (Prussian blue stain) and quantitative (ferrozine assay) technique. As expected, hepatic levels of hepcidin mRNA correlated to dietary iron intake in HJV +/+ mice. Surprisingly, hepcidin mRNA expression was likewise responsive to dietary iron intake in HJV −/− mice,
