Figure legend: * Immunosuppressive drugs: MMF = mycophenolate mofetil; tac = tacrolimus;CSA = cyclosporine ** Antibiotics: Amox=amoxicillin; amox-clav=amoxicillin-clavulanate;cipro=ciprofloxacin; cefaclor=cefaclor; cefixime=cefixime; doxy=doxycycline; levo=levoflox-acin; metro=metronidazole; moxi=moxifloxacin; TMP-SMX=trimethoprim-sulfamethoxazole

Mo1888

Splenectomy Overcomes Therapeutic Insufficiency of Corticosteroids andInduces Prolonged Remission of Autoimmune Hepatitis in MiceRyutaro Maruoka, Nobuhiro Aoki, Masahiro Kido, Satoru Iwamoto, Hisayo Nishiura, AkiIkeda, Tsutomu Chiba, Norihiko Watanabe

BACKGROUND andAIMS: Themajority of patients with autoimmune hepatitis (AIH) initiallyrespond well to corticosteroids. However, it is difficult to achieve long-term remission aftermedication is discontinued. We recently developed a mouse model of spontaneous AIH andfound that dysregulated follicular helper T (TFH) cells in the spleen are responsible forinduction of AIH. In this study, using the mouse model of AIH, we examined whethersplenectomy can be an alternative treatment to overcome insufficiency of corticosteroid toachieve long-term remission for AIH. METHODS: We used the mouse model of fatal AIHin which neonatal thymectomy (NTx) had been performed on programmed cell death 1-deficient (PD-1-/-) mice. NTx-PD-1-/- mice were administered dexamethasone (DEX) beforeor after the induction of AIH, and splenectomy alone or in combination with DEX treatmentwas performed. RESULTS: Intraperitoneal injections of DEX in NTx-PD-1-/- mice from oneday after thymectomy suppressed dysregulated TFH cells in the spleen and prevented thedevelopment of fatal AIH. In contrast, although therapeutic injections of DEX after thedevelopment of AIH resolved liver inflammation and resulted in a significantly increasedsurvival rate, dysregulated TFH cells remained in the spleen, and discontinuation of DEXtherapy induced relapse of fatal AIH. Notably, either splenectomy following the DEX therapyor splenectomy alone after the development of AIH suppressed fatal AIH. CONCLUSIONS:In our mouse model of AIH, relapse of AIH after the cessation of corticosteroid therapy isdue to residual splenic dysregulated TFH cells and splenectomy overcomes this insufficiency,inducing the prolonged remission of AIH.

Mo1889

Clinical Features of Hepatitic Form of Primary Biliary Cirrhosis andTherapeutic Strategy at a Tertiary Referral CenterMakiko Taniai, Etsuko Hashimoto, Kazuhisa Kodama, Tomomi Kogiso, NorikoMatsushita, Nobuyuki Torii, Katsutoshi Tokushige, Keiko Shiratori

Aims: Patients with primary biliary cirrhosis (PBC) ordinarily show a good response toursodeoxycholic acid (UDCA) and have a good prognosis; however, some patients with PBCpresent with sustained high levels of serum aminotransferases under UDCA treatment andshould be treated with corticosteroids. This condition has been called PBC-autoimmunehepatitis (AIH) overlap syndrome, PBC with AIH features, and the hepatitic form of PBC;however, the naming, disease course, prevalence, and most effective way to identify thesepatients remain uncertain. We validated several criteria to select patients for treatment withcorticosteroids. Methods: We examined the data of 321 PBC patients to determine the Pariscriteria (Paris), the revised score, as revised by the International AIHGroup in 1999 (Revised),and the simplified score, as simplified by the same group in 2008 (Simplified). We set thecriteria to add corticosteroids the treatment of PBC patients as follows: alanine aminotransfer-ase level > 3-fold above normal, immunoglobulin G level > 1.1-fold above normal, andsevere interface hepatitis on liver biopsy. Results: In 321 PBC patients (females, 86%; medianage, 58 years), the ratio of patients diagnosed as AIH by each criteria were as follows: Paris,6.9%; Revised probable, 6.3% and definite, 0.9%; and Simplified probable, 12.8% anddefinite, 8.7%. A total of 29 patients were identified for corticosteroids treatment. Thesensitivity/specificity for the selection of these patients by each criteria were as follows: Paris,66 /100%; Revised probable, 66/99% and definite, 10/100%; and Simplified probable, 97/86% and definite, 100/100%. By Paris, 5 patients who were negative for serum anti-smoothmuscle antibody (ASMA) were not selected. By Simplified, 41 patients designated as probabledidn't need to be treated with corticosteroids. In patients who were selected, 9 cases werenot treated with corticosteroids for the following reasons: 1 had poor prognosis due toadvanced uterus cancer, 4 had liver failure, and 4 were aged >80 years. Of 20 patientstreated by corticosteroids, 15 showed good response to the therapy. Patients with poorresponse to corticosteroid therapy had the following characteristics: high serum alkaline

S-991 AASLD Abstracts

phosphatase level (ALP), negative for ASMA (20% in poor vs 80% in good response), andpositive for gp210 antibody (40% vs 0%). The prognosis of patients with good response tocorticosteroids was excellent for all; however, all 5 patients with poor response showed diseaseprogression, and 1 received a liver transplant and 1 died by hepatic failure. Conclusion: Thesensitivity and specificity of the patient selection for corticosteroids was 100% in the definitecategory of the Simplified score. The predictors for poor response to corticosteroids inpatients with hepatitic form of PBC were high ALP, ASMA negative and gp210 positive.

Mo1890

Prevalence and Phenotype of Inflammatory Bowel Disease in Patients WithPrimary Sclerosing CholangitisDep Huynh, John P. Bate, Jane M. Andrews, Richard Johnson, Marc LeMire, Garry Nind,Hugh A. Harley

Inflammatory bowel disease (IBD) is common in patients with primary sclerosing cholangitis(PSC) (range reported 23-90%) and has a distinct phenotype with milder but more extensivecolonic disease, backwash ileitis, rectal sparing and a higher rate of colorectal cancer.Previously published epidemiological studies suggest a north-south gradient in the associationof IBD in patients with PSC. Data from the southern hemisphere is lacking. Aim: To determinethe prevalence and phenotype of IBD in patients with PSC in an Australian population.Method: The clinical, imaging and pathological characteristics of a cohort of patients withdocumented PSC were determined by casenotes review. Clinical and demographic detailsrelevant to PSC and IBD were collected. The study was approved by the hospital ethicscommittee, and specific informed consent was obtained from all patients managed by unitconsultants in private practice. Results: 55 patients with PSC were identified, 54.5% male,mean age 46.9 years at PSC diagnosis. 41.8% had at least 1 episode of cholangitis. 3 (5.5%)patients had biopsy proven small duct disease with normal cholangiograms, 34.5% hadintrahepatic duct disease, 9.1% extrahepatic duct disease and 50.9% had both intrahepaticand extrahepatic duct disease. 18.2% of patients developed cirrhosis. There were 4 patientswith cholangiocarcinoma. 36/55 (65.5%) of patients had associated IBD with mean age atIBD diagnosis of 32 years (72% of IBD diagnoses preceding PSC). Ulcerative colitis (UC)affected 24 (66.7%) patients, 17 had pancolitis (2 with backwash ileitis), 3 had a distalcolitis, 1 had a proctitis, 3 had incomplete data in regards to disease location. Of the patientswith UC, 8 patients had rectal sparing. Crohn's disease (CD) affected 6 patients (16.7%),3 had ileocolonic disease, 3 had only colonic disease and all 6 patients had non-stricturing,non-penetrating disease (Montreal B1). There were 6 (16.7%) with inflammatory boweldisease, type unspecified (IBD-U) and all had a right sided colitis without definitive endos-copic or histological evidence of CD. Of the 36 patients with IBD, 12 patients have hadsurgery, 7 of which were for neoplasia. 5 had dysplasia-associated lesion or mass (DALM)and/or high grade dysplasia, 2 had right sided colorectal cancer. Summary: IBD is prevalent(65.5%) in patients with PSC. The majority have UC (67.9%) but in our study rightsided IBD-U was also common (16.7%). UC in patients with PSC was characterised by apredominance of pancolitis (81%). More extensive colonic involvement is also seen in CD.In total, over half (55.6%) of patients with IBD had rectal sparing. In patients with CD (n=6), disease was mild. DALM, high grade dysplasia or colorectal cancer occurred in 19% ofpatients with PSC-IBD, but in over a quarter (29%) of those with PSC-UC.

Mo1891

Normalization of Alkaline Phosphatase in Patients With Primary SclerosingCholangitis is Associated With Normal Liver Stiffness on Magnetic ResonanceElastographyMohamad Imam, Jay Talwalkar, Richard L. Ehman, Keith D. Lindor

Aim: To determine if normalization of alkaline phosphatase is related to liver stiffness onmagnetic resonance elastography (MRE) in patients with primary sclerosing cholangitis (PSC)Methods: We identified patients with a confirmed diagnosis of PSC who underwent MREbetween 2007 and 2011. Patients were classified as having abnormal (> 2.9 Kilopascals) ornormal (≤ 2.9 Kilopascals) liver stiffness during evaluation. We compared alkaline phosphat-ase levels to the upper limit of normal (126 IU/ml). Alkaline phosphatase was consideredto normalize if one or more values during follow up were normal. Chi square tests wereused to assess the association of alkaline phosphatase normalization with liver stiffness onMRE. Results: Fifty three patients had a confirmed diagnosis of PSC and underwent MRE.Among 18 patients with normal liver stiffness values, 13 patients (72%) experienced persistentnormalization of serum alkaline phosphatase levels as compared to 5 patients (28%) withpersistently elevated alkaline phosphatase levels. Conversely, 23 of the 35 patients withabnormal liver stiffness (66%) had persistently elevated serum alkaline phosphatase levelsin contrast to only 12 patients (34%) with normalization of alkaline phosphatase levelsduring the follow up period (p< 0.009). The predicted 4 year survival rates by Mayo RiskScore in patients with normal liver stiffness was 94% as compared to 77% in patients withabnormal liver stiffness. Demographic and clinical features of the cohort are shown in Table1. Histological stage of PSC when available is shown in Table 2. Conclusion: Patients withnormalization of serum alkaline phosphatase levels were significantly more likely to havenormal mean liver stiffness by MRE when compared to patients with elevated serum alkalinephosphatase levels.This preliminary data supports the observation that serum alkaline phos-phatase may be a valid surrogate biomarker for treatment response in PSC.

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