$240 POSTERS and remained unchanged or was reduced in 9 patients. The increase in BMD was associated with lower bilirubin levels but not with compliance, age or baseline BMD. These results suggest that once-weekly alendronate is more effective and has a better tolerability profile than daily dosing in patients with PBC and low bone mass. The effects of alendronate on BMD are lower in patients with higher indices of cholestasis. • GENETIC VARIANTS OF HEPATOBILIARY TRANSPORTER AND NUCLEAR RECEPTOR GENES AND RESPONSE TO URSODEOXYCHOLIC ACID IN PRIMARY BILIARY CIRRHOSIS V. Barbu 1, C. Ping2, C. Corpechot 3, Y. Chr~tien 1, F. Matsuda 2, O. Chazouilli+res 3, T. Simon4, R.E. Poupon 3, R. Poupon3. 1Facultd de Mddecine Pierre et Marie Curie, INSERM U680, Hospital Saint-Antoine, Paris', France," 2Centre National du Gdnotypage, Evry, France," 3Centre de Rdfdrence des Maladies Inflammatoires des voies biliaires, Hospital Saint-Antoine, Paris', France," 4URC-EST, Hospital Saint-Antoine, Paris, France Background and aim: Ursodeoxycholic Acid (UDCA) delays the pro- gression of Primary Biliary Cirrhosis (PBC) to end-stage liver disease and enhances survival. However, some patients even diagnosed in the early stage of disease fail to respond to UDCA. The aim of the study was to determine the relationships between allelic variations of hepatobiliary transporter and nuclear receptor genes and failure of UDCA in PBC. Patients and Methods: DNA was extracted from lympho-mononuclear cells of 147 PBC patients diagnosed and followed-up at Hospital Saint- Antoine for a median duration of 5 years. All the patients received UDCA (13 15mg/kg/day) and were monitored every six months. Criteria of failure of UDCA were the following: development of hyperbilirubinemia (>17 ?M) or of cirrhosis or occurrence of digestive bleeding or ascites or liver transplantation or death due to liver failure. The polymorphisms of the following genes were studied: transporters (MDR1/ABCB1, MDR3/ ABCB4, BSEP/ABCB11, MRP2/ABCC2, CFTPUABCC7, AE2/SLC4A2, NTCP/ SLC10A1, ASBT/SLC10A2, OATPA/SLC21A3, FIC1/ATP8B1, SCP2, ABCG5, ABCG8) and nuclear receptors (FXPUNR1H4, PXPUSXPU NRII2, LXRA/NR1H3). Haplotype tag single nucleotide polymorphisms (ht SNPs) were identified. The genotyping of the ht SNPs was performed with Taqman technology using the apparatus ABI Prism SDS 7900 and by direct sequencing. Fisher's exact test and log-rank test were used for statistical analysis. Results: Forty-five ht SNPs were selected for the 16 studied genes. The following ht SNPs of MDR1 (rs 1922242, rs2214102) and SCP2 (rs728565) were significantly associated with UDCA failure (respectively p < 0.03 and p < 0.02). Mutated SCP2 variant was associated with a good response while MDR1 variant was linked to a poor response to UDCA. Conclusion: These results are consistent with our previous data indicating that the severity of PBC at diagnosis was in part related to allelic variations in hepatobiliary transporter genes. Further, the present findings show for the first time that the response to UDCA is linked to ABCB1 polymor- phisms and thus, to the ability to control translocation of xenobiotics out of the cell. Linkage to SCP2 emphasizes that cholesterol trafficking is critically involved in PBC severity and response to UDCA. • MATURE LYMPHOCYTES ARE REQUIRED FOR THE CHARACTERISTIC HISTOLOGICAL MANIFESTATIONS IN A MOUSE MODEL FOR AUTOIMMUNE HEPATITIS K. Presser1., K. Reifenberg2, T. Bauer 3, T. Longerich4, A. Quaas 5, M. Blessing6, C. Schnabel 7, A.W. Lohse 1, C. Schramm1. 1Medical Clinic, University Hospital Hamburg Eppendorf Hamburg, Germany," 2ZVTE, University Hospital Mainz, Mainz, Germany," 31. Medical Clinic, University Hospital Mainz, Mainz, Germany," 4Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany," 5Institute of Pathology, University Hospital Hamburg Eppendorf Hamburg, Germany," 6BBZ, University of Leipzig, Leipzig, Germany," 7Institute for Clinical Chemistry, University Hospital Hamburg Eppendorf Hamburg, Germany Background and Aim: Livers of patients with autoimmune hepatitis (AIH) show elevated IFN-y expression. The aim of this study was to evaluate transgenic mice overexpressing IFN-7 as a model for AIH and to define the pathophysiological role of lymphocytes within this model. Methods: Transgenic mice overexpressing IFN-7 under the liver specific SAP-promoter were studied up to an age of 47 weeks. Liver enzymes, gamma-globulins, autoantibodies and histological hepatitis score were evaluated. In order to study the influence of lymphocytes on chronic hepatitis, SAP-IFN-7 mice were crossed with RAG1 / mice lacking mature T and B cells. Results: In comparison to wildtype, SAP-IFN-7 mice had significantly increased serum transaminases (ALT: 496• vs. 45• for SAP- IFN-7 vs. wildtype, p < 0.002), a higher histological score (mHAI: 8• vs. 1• p <0.001), elevated gamma-globulin levels (14.8• vs. 11.97• mm2 for SAP-IFN-7 vs. wildtype, p 0.0535) and antinuclear antibodies were detected by immunofluorescence only in SAP-IFN-7 mice, thereby featuring several characteristics of AIH. In comparison to SAP-IFN-7 transgenic mice, transgenic mice lacking mature T and B cells had similar transaminase levels at six months (110.64• vs. 114.06• for SAP-IFN-7 mice vs. SAP-IFN-7 • RAG1 / mice) and a similar overall hepatitis score (9.2• vs. 7.8• However, the severity of portal (2.6• vs. 1.2• p <0.002) and periportal hepatitis (2.3• vs. 1.6• p < 0.04) was significantly attenuated in transgenic mice on the RAG1 / background. Conclusions: Mice overexpressing IFN-7 in the liver resemble AIH in many features. Using this model we hereby demonstrate the importance of mature lymphocytes for the development of portal and periportal hepatitis, key histological characteristics of AIH. ~HIGH FREQUENCY OF X CHROMOSOME ABNORMALITIES IN SHORT STATURE WOMEN WITH UNEXPLAINED ELEVATED LIVER ENZYMES D. Roulot 1'2, V. Malan 3, V. Bourcier 1, B. Benzacken 3, M. Ziol 4, M. Beaugrand 1. 1Service d'H@atologie, Hdpital .lean Verdie~ Bondy, France," 2Unitd d'H@atologie, Hdpital Avicenne, Bobigny, France," S Service d 'Histologie-Embryologie et cytogdndtique, H@ital .lean Verdie~ Bondy, France," 4Service d 'Anatomo-pathologie, Hdpital .lean Verdie~ Bondy, France Background and Aims: Liver changes are common in patients with Turner syndrome (TS). The complete loss of one chromosome X is gen- erally associated with typical morphotype whereas other chromosome X abnormalities may result only in short stature and remain undiagnosed. Thus, we prospectively investigated the prevalence of chromosome X abnormalities in women with short stature and unexplained elevated liver enzymes, a common situation in clinical practice. Patients and Methods: We prospectively included in this monocentric two years study, 31 patients with reduced height (below 155 cm or below 16 cm in case of marked discordance with family members) and unexplained elevated liver enzymes, either transaminases (n 23), and/or GGT (n 29)