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scorroborates the protective effect of rifaximin in the ITT population. The most influentialprognostic factors for maintenance of remission were age, and baseline MELD score.

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Enhanced TLR Signaling Breaks Endotoxin Tolerance in Human BiliaryEpithelial Cells in END-Stage Chronic Inflammatory Liver DiseaseTobias Mueller, Andreas Pascher, Peter Neuhaus, Bertram Wiedenmann, Thomas Berg

BACKGROUND: TLR signaling in biliary epithelial cells (BECs) is tightly controlled toprevent excessive innate immune responses in the healthy liver. We examined the effect ofchronic inflammation on TLR-mediated endotoxin tolerance in human BECs in patientswith end-stage chronic inflammatory liver disease (ESLD), which protects the host frompermanent BEC activation in the face of ubiquitous intestinal TLR ligands in the bile andportal venous blood. METHODS: We examined patients undergoing liver transplantationfor immune-mediated (PBC, PSC), alcoholic and viral (chronic hepatitis B and C) ESLD.Northern blots, real-time RT-PCR, western blots and immunocytochemistry were used formRNA and protein expression studies of innate immune proteins in whole ESLD tissue andisolated primary BECs. Flow cytometry for incorporated endotoxin, ELISAs for secreted pro-inflammatory mediators such as IL-6, IL-8, and MCP-1, NF-κB reporter assays and TLRover-expression studies were used for functional studies. RESULTS: Freshly isolated humanBECs in ESLD showed increased TLR activation profiles and markedly enhanced ICAM-1expression, which have recently been linked to decreased hepatic endotoxin tolerance. WholeESLD tissue exhibited increased expression of IFN-γ and TNF-α. Affected BECs depictedactivated IFN-γ-dependent genes such as CXCL9, CXCL10 and CXCL11. We also foundenhanced activation of IRF-1 and STAT1 in activated BECs, which have been shown topromote TLR signaling. These findings suggested that chronic inflammation led to enhancedTLR-mediated innate immune responses and decreased endotoxin tolerance in affected BECsin ESLD. In line with this hypothesis, primary human BECs isolated from patients withearly disease stages depicted normal TLR and IL-6, IL-8, MCP-1 and ICAM-1 expression.These data suggested that increased PRR signaling and diminished endotoxin tolerance inBECs did not play a role in the primary pathogenesis of these diseases and argued for asecondary phenomenon due to chronic inflammation. Further In Vitro studies confirmedthat pro-inflammatory cytokines and repetitive endotoxin challenges disrupted homo- andhetero-tolerance to endotoxins in BECs. Enhanced TLR surface expression and subsequentlyincreased endotoxin incorporation in cytokine-primed BECs contributed to increased TLRsensitivity. CONCLUSIONS: Chronic inflammation promotes a state of hyper-responsivenessto TLR ligands in ESLD and breaks the protective endotoxin tolerance in BECs. Loss of TLRtolerance appear to be especially deleterious in the face of increased intestinal endotoxinlevels, which have been described in patients with ESLD of different etiologies.

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The Impact of Cirrhosis or Prior Liver Transplant On Obstetrical Outcomes: ANational StudySanjay K. Murthy, Jenny Heathcote, Geoffrey C. Nguyen

Objectives: The impact of cirrhosis or prior liver transplant on maternal and fetal healthduring pregnancy has not been well characterized. We sought to compare health outcomerates in pregnant women with a history of cirrhosis or liver transplant to pregnant womenwithout liver disease. Methods: A population-based cohort study of women admitted forlabor and delivery to U.S. hospitals between 1998 and 2005 was conducted using data fromthe Nationwide Inpatient Sample database. Pregnant women with a history of cirrhosis orliver transplant were compared to pregnant women without liver disease (controls) forvarious obstetrical and medical health outcomes. Results: Among pregnant women, 187women with cirrhosis and 86 women with a prior liver transplant were compared to 662,408women without liver disease. Women with cirrhosis or prior liver transplant had higherrates of co-morbid illness and admission to an academic centre, and lower rates of privatehealth insurance, than general obstetrical patients (p<0.0001 for all comparisons). Therates of Cesarean section, preterm delivery, peripartum infection and pregnancy-inducedhypertension were higher in both groups of patients, while rates of death, venous thromboem-bolism, malnutrition, placental abruption and peri-partum blood transfusion were increasedspecifically in cirrhotic women (Table 1). The adjusted mean length of hospital stay was32% greater among cirrhotic women (95% CI: 18% - 49%) and 30 % greater among womenwho were status post-liver transplant (95% CI: 13% - 50%) as compared to pregnant womenwithout liver disease. Conclusions: Pregnant women with a history of cirrhosis or livertransplant are at higher risk of developing numerous adverse obstetrical and medical healthevents than women without liver disease. Further prospective studies are warranted toconfirm these findings and to assess the benefit of early involvement of a multidisciplinaryhealth care team in the care of such patients.Table 1. Adjusted Odds Ratios of Adverse Outcomes in Hospitalized Obstetrical PatientsBased on Liver Status

A-28AGA Abstracts

* Compared to pregnant women without liver disease ** No cases in liver transplant group

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Intraductal Ultrasonography Combined with Percutaneous TranshepaticCholangioscopy for the Preoperative Evaluation of Longitudinal Tumor Extentin Advanced Hilar CholangiocarcinomaHee Man Kim, Jeong Youp Park, Kyung Sik Kim, Mi-Suk Park, Myeong-Jin Kim, YoungNyun Park, Seungmin Bang, Si Young Song, Jae Bock Chung, Seung Woo Park

Background: In hilar cholangiocarcinoma, evaluation of tumor extension to secondarybifurcation is important to determine resectability. Aim: To investigate accuracy of intraductalultrasonography (IDUS) combined with percutaneous transhepatic cholangioscopy (PTCS)for evaluation of the longitudinal extension to secondary bifurcation in advanced hilarcholangiocarcinoma with Bismuth type IIIa, IIIb and IV. Methods: Patients with hilar cholan-giocarcinoma were enrolled. Patients underwent multidetector computed tomography(MDCT) and magnetic resonance cholangiography (MRC) for initial tumor staging. In caseof potentially resectable tumor, percutaneous transhepatic cholangioscopy (PTCS) withbiopsy was performed at the left or right bile duct in Bismuth type IIIa or IIIb, respectively,to evaluate longitudinal tumor extent. In case of suspicious Bismuth type IV, PTCS wasperformed at the liver section anticipated to be preserved in surgical treatment. After PTCS,IDUS was performed sequentially. Based on information from MDCT, MRC, PTCS andIDUS, surgery with curative intent was performed and histological examination was made.Results: From June 2006 to November 2008, 25 patients with hilar cholangiocarcinomawere enrolled and 20 patients were evaluable. The accuracy of MDCT, MRC, PTCS withbiopsy and IDUS in assessing longitudinal tumor extent was 80.0%, 84.2%, 90.0% and85.0%, respectively, compared with post-operative histologic findings. In 18 patients withBismuth type IIIa, IIIb or IV, the accuracy of MDCT, MRC, PTCS with biopsy and IDUSwas 77.8%, 77.8%, 94.4% and 88.9% on longitudinal tumor extent, respectively. Thecombination of IDUS and PTCS produced a diagnostic accuracy of 100% on longitudinaltumor extent. IDUS and PTCS with biopsy prevented an unnecessary surgery in one patientunderestimated by MDCT and MRC. In two patients overestimated as Bismuth type IV byMDCT and MRC, IDUS properly evaluated Bismuth type. Conclusions: The combinedmodality of IDUS and PTCS with biopsy demonstrates high accuracy in assessing longitudinaltumor extent to determine resectability, which helps to make an optimal surgical plan inadvanced hilar cholangiocarcinoma, especially in Bismuth type IIIa, IIIb and IV.

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Serum TNF-α, IL-10 and IL-18 Levels and the Cytokine Releasing Activity ofCd4cd57αβTCR-Positive T Cells in HCV-Related Hepatocellular CarcinomaPatients During Tumor ProgressionTatsuya Shiraki, Eiji Takayama, Hirohito Magari, Yoshiyuki Mori, Kosaku Moribata, NaokiShingaki, Hisanobu Deguchi, Izumi Inoue, Takao Maekita, Mikitaka Iguchi, KimihikoYanaoka, Hideyuki Tamai, Kenji Arii, Masashi Oka, Masao Ichinose

BACKGROUND:Previous studies have indicated that serum IL-18 or IL-10 levels may besignificant prognostic determinants in patients with hepatocellular carcinoma (HCC) orgastric cancer. In addition, we have previously reported that an increase of CD4CD57αβ Tcells in peripheral blood (PB) reduces IFN-γ production in subjects with advanced gastriccancer and that there is a significant negative correlation between the increase of CD4CD57αβT cells and patient prognosis (Gastroenterol 2007;32:A621). In the present study, we investig-ated the basal serum levels of a series of cytokines (IFN-γ, TNF-α, IL-12, IL-18, and IL-10) and also the kinetics and lipopolysaccharide (LPS)-stimulated cytokine releasing activityof CD4CD57αβ T cells in the PB of HCV-related HCC patients in order to determine therelationship between tumor progression and the kinetics of anti-tumor immunity in patientswith HCV-related HCC. METHODS:Ninety-six HCV-related HCC patients treated between2006 and 2008 at the Wakayama Medical University (Wakayama, Japan) were enrolled inthis study [62 men, 34 women; age 71.2 ± 8.2 years (median ± SD), range 42-88 years].A 5-ml sample of PB was collected from each patient. Aliquots of PB were incubated withLPS (final concentration, 1 μg/ml) and the culture supernatant was collected. Separated serafrom PB and the culture supernatant were assayed for a series of cytokines with an ELISAkit. The proportion of CD4CD57αβ T cells among PB mononuclear cells (PBMCs) wasanalyzed using a flow cytometric analyzer. RESULTS:Serum cytokine levels of TNF-α, IL-18 and IL-10 were significantly elevated with advancing stages of HCC, while serum IFN-γ levels were undetectable throughout the stages of HCC. The releasing activity of IFN-γfrom PBMCs stimulated with LPS significantly decreased in a stepwise manner with tumorprogression (stage I: 69.7 ± 72.7, stage II: 19.7 ± 44.1, stage III: 12.3 ± 23.5, stage IV: 5.3± 5.9 IU/ml, p < 0.01). The present study, using an In Vitro culture system clearly indicatedthat tumor progression reduced the anti-tumor immunity of HCC patients. The numbersof CD4CD57αβ T cells increased with tumor progression in HCV-related HCC patients(stage I: 38.2 ± 23.5, stage II: 46.5 ± 39.9, stage III: 73.3 ± 48.5, IV: 33.5 ± 26.5, p <0.01). Taken together, these results show that the increase of these T cell subjects is