Introduction Short-term outcome of treated AIH is good but liver disease may progress despite treatment. We previously reported on AIH patients presenting to our (non-transplant) centre between 1971–2007 (1). Case-capture was complete only after 1987, possibly resulting in underestimated mortality. We aim to assess outcome and temporal trends in patients presenting between 1/1/1987 and 31/12/2016. Method We assessed overall survival (life table analysis) and standardised mortality ratio (SMR; compared to regional population data, considering liver transplant as death). Patients presenting between 1987–2006 were compared with those since 2007. Results From 345 patients (275 female) there were 106 deaths (28 liver-related deaths) and 8 transplanted. Overall 10- and 20 year death/transplant rates were respectively (mean±SEM) 24%±3% and 53%±5% (all cause) and 10%±2% and 21%±4% (liver-related). SMR was (mean(95% CI)) 1.77 (1.4–2.1) overall and was 5.16 (1.7–8.6), 1.84 (1.34–2.5) and 1.51 (1.11–1.92) respectively in those presenting aged <45, 45–65 and >65 years. SMR was close to unity for non-liver deaths. Conclusion Overall survival and SMR are similar to those we previously reported. AIH patients still have excess long-term mortality due to their liver disease, including those presenting at age over 65 (new observation). Patients presenting since 2007 compared to those presenting earlier, are older, less likely to have cirrhosis and have a trend towards lower all-cause short-term mortality. Reference . Hoeroldt B, McFarlane E, Dube A, Basumani P, Karajeh M, Campbell J, Gleeson D. Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant centre. Gastroenterology2011; 140:1980 Disclosure of Interest None Declared

Introduction If immunosuppressant therapy (IST) is withdrawn in patients with autoimmune hepatitis (AIH) when remission is achieved, 50–70% will have a disease relapse within 12 months. Thus, many patients receive long-term maintenance IST. However, IST has potential side effects, including an increased cancer risk. Recent studies suggest a lower AIH relapse rate if IST is withdrawn at a later stage in the disease. Data are lacking in regard to long-term outcome following IST withdrawal. Methods Retrospective audit of long-term outcome of AIH following withdrawal of IST. A total of 282 patients with definite or probable AIH by International AIH Group criteria, had presented to our Unit between 1971–2015 and had achieved normalisation of serum ALT within 12 months of starting IST (prednisolone plus azathioprine, or mycophenolate if azathioprine intolerant). From these, we found 25 patients in whom all IST was subsequently discontinued. We assessed outcome in these patients, in comparison to those who continued IST. Follow-up was until last serum ALT for calculating relapse rate and until death or last known to be alive for calculating survival rates. Results The 25 patients (21 female, age at diagnosis 50 (8–68) years) had been on IST before withdrawal for 3.9 (0.1–22.4) years. Five had cirrhosis at presentation. All patients had normal serum ALT and globulins at time of withdrawal except one patient with acute pancreatitis. Reasons for IS withdrawal were: cancer (6), infections (3), side effects (4), frailty (6) patient choice (6), doubt about diagnosis (subsequently resolved) (1). Relapses occurred in 7 patients (28%) after 1.6 (0.5–9.6) years. Relapse rates were 15%, 20% and 28% after 2, 5 and 10 years respectively. All patients achieved re-normalisation of serum ALT within 3 months of re-starting therapy (prednisolone 10–40 mg/day) plus (in 5 patients) azathioprine or mycophenolate, subsequently continued as maintenance therapy. Over follow up (from IST withdrawal) of 4.2 (1.2–25.1 years), no patient developed liver decompensation, variceal bleeding or hepatocellular carcinoma. Six patients died after 4 (3.3–15.9) years; none due to liver disease or following AIH relapse. Patients stopping IST (n = 25) had, compared to those who continued IST (n = 257) higher 10- and 20 year survival (99±4% and 79±9% respectively vs 78±3% and 48±4% p = 0.021). Conclusion In patients with AIH who achieve remission a trial of withdrawal of IS therapy is associated with (a) a lower disease relapse rate than previously reported, (b) no liver adverse events and (c) no reduction in long-term survival compared with patients who continue on long-term IS therapy. Disclosure of Interest None Declared

OBJECTIVE:The aim of this study was to evaluate UK trainee experience in endoscopy for acute upper gastrointestinal bleeding (AUGIB).METHODS:Data was prospectively collected from all patients presenting to South Yorkshire Hospitals with AUGIB from September 2011 to December 2011 and compared with data from 1996. Concurrently, all gastroenterology trainees registered with the British Society of Gastroenterology were invited to respond to a web-based questionnaire regarding their experience in AUGIB management.RESULTS:77% (589/766) of the patient cohort underwent endoscopy for AUGIB; 15% (90/589) were performed by trainees. 7.2% (9/125) of the out of hours endoscopy case load was performed by trainees; all were low-risk or medium-risk cases (pre-endoscopy Rockall score ≤4). During the study period, dual therapy was delivered by a trainee on only four occasions. Comparison with the 1996 cohort demonstrated a marked reduction in the number of trainee performed endoscopies (76% vs 15%; p<0.001). Questionnaires were returned by 51% (245/478) of British Society of Gastroenterology trainees. 81% (198/245) thought that <10% of the gastroscopies they had performed involved therapeutic intervention. 23% (57/245) felt they would not be competent in AUGIB endoscopy by completion of specialty training.CONCLUSIONS:This study demonstrates the decline over time in trainee experience in AUGIB endoscopy. It also highlights a lack of trainee exposure to more challenging cases, out of hours endoscopy and therapeutic procedures. Furthermore, trainees are concerned that a level of competency may not be attained during specialty training. We advocate reviewing UK endoscopic training provision for AUGIB to ensure that experienced endoscopists are produced to meet future service needs.

Introduction Acute upper GI bleeding (AUGIB) is a common gastrointestinal problem associated with significant mortality.1 Whilst numerous factors have been shown to influence mortality in these individuals including co-morbidity and time of bleeding, variation in local practises may have a bearing on outcomes. This study evaluates whether facilities provided at differing centres can influence outcomes of AUGIB, with findings compared to the BSG National Audit (Hearnshaw et al 2011). Methods Data was prospectively collected from five South Yorkshire hospitals (Northern General Hospital, Royal Hallamshire Hospital, Rotherham District General Hospital, Chesterfield Royal Hospital and Barnsley District General Hospital) between Sept-Dec 2011. This included demographic, clinical and endoscopic findings in all AUGIB patients, alongside 30-day mortality outcomes. Patients were risk stratified using pre-endoscopy Rockall scores with comparisons made with national audit results using standardised mortality ratios (SMR). In addition, service provision for AUGIB within each unit was collected. χ2 analysis was used to compare categorical data, with p values < 0.05 considered significant. Results A total of 796 patients (438 male, median age 65 years, range 16–86) were admitted at all sites with AUGIB during the 3-month study period. Of these patients, 33.7% (268/796) had a pre-endoscopy Rockall score of 6 or above, significantly higher than the 5.9% identified in the national audit (p = < 0.001). All hospitals in South Yorkshire had out of hours (OOH) endoscopy rotas (national audit = 52%), a nurse on call rota (national audit = 37%) and facilities to undertake OOH endoscopy (national audit = 92%). Whilst no statistical difference was identified in mortality between individual hospitals in South Yorkshire (p = 0.406), both risk-standardised mortality ratios and inpatient mortality in South Yorkshire were significantly lower than national audit findings (Table 1). Abstract PTU-041 Table 1 Comparisons between South Yorkshire and National Audit populations South Yorkshire Data (n= 796) National Audit (n= 6750) p-value Median Pre-Endoscopy Rockall Score 5 3 N/A New Admissions Mortality 7.3% 7% 0.69 Inpatient Mortality 15.9% 26% 0.02* Overall mortality 8.5% 10% 0.21 * Significant result Conclusion Despite a higher pre-endoscopy Rockall Score in our cohort, both our risk adjusted mortality and inpatient mortality rates were significantly lower than the national audit findings. We believe that these outcomes are reflective of having dedicated GI bleed services, with provision and staffing of OOH endoscopy rotas, enabling us to provide quicker and more comprehensive services to our patients. Disclosure of Interest None Declared

Introduction UGIB is a common emergency frequently requiring endoscopic intervention. Training in therapeutic endoscopy for UGIB is not mandatory. Furthermore UGIB endoscopic experience may be diminished by the European Working Time Directive and a Consultant delivered service. There has been no published data on trainees’ opportunities for UGIB endoscopic experience. This study evaluates GI trainee experience in the South Yorkshire (SY) region and nationally. Methods Rockall scores for patients requiring an endoscopy for an UGIB (n = 622, 5 hospitals) was prospectively collected in SY between Sept-Dec 2011. Trainee experience from this cohort was then compared with a historical SY UGIB cohort (n = 274) from 1996. Nationally, all BSG trainees (n = 478) were invited to respond to a custom designed web based questionnaire (Nov-Dec. 2012). Information was collected about OGD competency (both diagnostic and therapeutic) and trainees’ confidence of acquiring sufficient endoscopic skills in UGIB prior to completing specialty training. Results Regionally, comparison between the 2011 and 1996 SY UGIB cohorts demonstrated comparable 30-day mortality rates (8.5% vs 8.1%, p = 0.78), with similar median post-endoscopy Rockall scores (6 v 5). When comparisons were made between trainee and non-trainee performed procedures, no mortality difference was identified (p = 0.286). However, when comparing trainee undertaken procedures between the two cohorts, a significant decline was observed with 76% (208/274) of endoscopic procedures for UGIB being performed by trainees in 1996 compared with only 16% (97/622) in 2011 (p < 0.0001). Nationally, questionnaires were returned by 51% (245/478) of BSG trainees (median = 4 years registrar training, range 1–9 years). Of these, 42% (104/245) had completed a basic upper GI endoscopy training course and 40% a therapeutic course. Median number of OGD’s performed by trainees was 500, with therapeutic exposure < 10% in 76% of cases. 23% (57/245) of trainees felt their endoscopic skills in UGIB will be insufficient at the time of specialty training completion. Conclusion This study objectively demonstrates a decline in regional training for gastroenterology trainees in UGIB endoscopic procedures. Furthermore our regional audit is supported by the National audit, which suggests that trainees across the UK are both limited in their opportunities and concerned that a level of competency may not be attained during registrar training. We advocate reviewing UK endoscopic training provision for UGIB ensuring qualified and confident endoscopists are produced to meet future service needs. Disclosure of Interest None Declared

Introduction Gastrostomy feeding is an effective means of providing enteral nutrition to patients who have functionally normal gastrointestinal tracts but who cannot meet their nutritional requirements because of an inadequate oral intake. Whilst improvements in outcome measures such as nutritional status and mortality have been demonstrated in certain patients undergoing gastrostomy insertion, there remains a paucity of work evaluating another important health outcome measure, which is health related quality of life (HRQoL). Furthermore no previous study has looked at the impact on carers’ HRQoL when considering all referral indications for gastrostomy. This prospective, multicenter study evaluates HRQoL in both gastrostomy patients and their carers, with comparisons made with a population control group. Methods 61 patients (mean age 68 years) and 58 carers (mean age 65 years) were prospectively recruited from 4 hospitals in South Yorkshire between Feb-Dec 2012. All individuals had HRQoL evaluated prior to gastrostomy insertion, with repeated measurements undertaken at 3 months. Assessment was undertaken using EQ-5D, a validated assessment tool and preferential measure used by NICE, producing scores between 0 for dead and 1 for perfect health. Findings were then compared with a separate cohort of population controls (n = 419), to determine if differences existed in HRQoL. Non-parametric statistical analysis was undertaken using a Wilcoxon Rank test to compare longitudinal paired EQ-5D scores, and a Mann-Whitney test to compare EQ-5D scores between groups, with p values < 0.05 considered significant. Results 61 gastrostomy patients have been assessed to date. Of these, 3 died prior the 3 month reassessment post insertion. No significant change was shown in mean EQ-5D scores in either the gastrostomy patients (0.74 versus 0.73, p = 0.11) or their carers (0.96 versus 0.97, p = 0.30) at 3 months following gastrostomy insertion. When compared to population controls, carers had comparable scores to the population controls unlike the gastrostomy patients who had significantly lower mean EQ-5D scores (0.73 versus 0.94, p < 0.0001). Conclusion This study demonstrates that HRQoL does not significantly improve for patients or their carers following gastrostomy insertion. Given that gastrostomy feeding has no positive effect on HRQoL, questions must be raised as to the merits of this intervention if it only serves to improve physiological outcomes. Disclosure of Interest None Declared.

Introduction Acute upper GI bleeding (AUGIB) is a common gastrointestinal problem associated with significant mortality.1 Whilst numerous factors have been shown to influence mortality in these individuals including co-morbidity and time of bleeding, variation in local practises may have a bearing on outcomes. This study evaluates whether facilities provided at differing centres can influence outcomes of AUGIB, with findings compared to the BSG National Audit (Hearnshaw et al 2011). Methods Data was prospectively collected from five South Yorkshire hospitals (Northern General Hospital, Royal Hallamshire Hospital, Rotherham District General Hospital, Chesterfield Royal Hospital and Barnsley District General Hospital) between Sept-Dec 2011. This included demographic, clinical and endoscopic findings in all AUGIB patients, alongside 30-day mortality outcomes. Patients were risk stratified using pre-endoscopy Rockall scores with comparisons made with national audit results using standardised mortality ratios (SMR). In addition, service provision for AUGIB within each unit was collected. χ2 analysis was used to compare categorical data, with p values < 0.05 considered significant. Results A total of 796 patients (438 male, median age 65 years, range 16–86) were admitted at all sites with AUGIB during the 3-month study period. Of these patients, 33.7% (268/796) had a pre-endoscopy Rockall score of 6 or above, significantly higher than the 5.9% identified in the national audit (p = < 0.001). All hospitals in South Yorkshire had out of hours (OOH) endoscopy rotas (national audit = 52%), a nurse on call rota (national audit = 37%) and facilities to undertake OOH endoscopy (national audit = 92%). Whilst no statistical difference was identified in mortality between individual hospitals in South Yorkshire (p = 0.406), both risk-standardised mortality ratios and inpatient mortality in South Yorkshire were significantly lower than national audit findings (Table 1). Conclusion Despite a higher pre-endoscopy Rockall Score in our cohort, both our risk adjusted mortality and inpatient mortality rates were significantly lower than the national audit findings. We believe that these outcomes are reflective of having dedicated GI bleed services, with provision and staffing of OOH endoscopy rotas, enabling us to provide quicker and more comprehensive services to our patients. Disclosure of Interest None Declared

Introduction A recent report1 suggested that initial treatment of Autoimmune Hepatitis (AIH) with high-dose prednisolone results in more rapid normalisation of serum ALT and (by implication), improved outcome. However, we have reported2 that persisting histological activity in AIH (Ishak necroinflammatory score (NIS) >3), despite serum ALT normalisation, is associated with fibrosis progression and increased mortality. Here, we aimed to identify, retrospectively, disease or treatment related factors associated with attaining histological remission. Methods We studied 111 patients with AIH (93 female, median (range) age at diagnosis 57 (14–77) years treated with prednisolone plus azathioprine/mycophenolate, who had attained normalisation of serum ALT and had available follow-up biopsy. Results Starting daily doses of prednisolone and of azathioprine were 30 (10–60) and 50 (25–150) mg respectively. Time taken to achieve normal serum ALT after starting treatment was 8 (0–144) weeks and showed no correlation with any of: (a) gender, age, serum ALT, or globulin at presentation (b) NIS or fibrosis grade at diagnostic biopsy, (c) starting dose of prednisolone or azathioprine. Biopsy was repeated 26 (12–90) months after starting treatment. 72 patients (65%) attained histological remission. Comparing these with the 37 patients not in histological remission, there were no significant differences in age, gender, presenting serum ALT, or in NIS or fibrosis stage at diagnostic biopsy. Neither were there differences in either (a) starting or cumulative dose of prednisolone or azathioprine (either absolute or corrected for body weight) or (b) time to achieve normal serum ALT. Only serum globulin at presentation was lower in those who achieved histological remission (42 vs 49 g/l, p=0.01). On multivariate analysis, NIS at follow-up biopsy was independently associated with serum ALT at time of biopsy (p≤0.001) but with none of above baseline, treatment or early response -related variables. Conclusion We could not identify baseline or treatment -related variables associated with (and thus, potentially predictive of) histological remission. Specifically, we could not establish that histological remission was related to either time to serum ALT normalisation or to starting or cumulative dose of prednisolone. Competing interests None declared. References 1. Schramm C, et al. Hepatology 2010;52:2247–82. 2. Hoeroldt BS, et al. Gut 2009;58:A18.

Introduction Hp causes peptic ulcer disease (PUD) and is potentially carcinogenic. Hp eradication is done in conditions like PUD, uncomplicated dyspepsia and persistent iron deficiency anaemia. ‘Test and treat’ implies testing specifically with intent to treat, if positive. CLO test is read in real time and acted on promptly. Hp serology is used in acute upper GI (UGI) bleed or endoscopy on PPI as CLO test is less sensitive. Results take 5–7 days by when in-patients have been discharged and positive Hp serology (Hp+ve) results overlooked. This audit was prompted by two such missed cases of Hp+ve PUD with rebleed in one. Aim To review action taken on Hp+ve results in our hospital, assess factors contributing to inaction, impact on patient care and remedial steps needed. Methods Retrospective study of all patients with Hp+ve requested by hospital clinicians in 12 months (1 April 2009 to 31 March 2010). Serology data from our microbiology department was matched with subsequent urea breath tests (UBT), our standard test to confirm eradication. Patients with sequential serology and UBT were deemed to have received eradication. Case notes of the others were reviewed for test indication, point of first contact, gastroscopy findings (if done), eradication recommendation by endoscopist, specialist nurse (SpN) contact, reason for non-eradication and any complications. Conclusion 1 in 6 Hp+ve not eradicated; 21/33 results not reviewed. Factors for inaction: multiple test sources (clinic, ward, endoscopy), lack of single contact of point (poor use of SpN support), unclear advice from endoscopists. Recommendations In routine clinical practice, test Hp serology only with intent to treat positives. SpN in endoscopy unit to be single point for contact, review of results and action on Hp+ve results: If +ve, initiate and ensure successful eradication where recommended; contact clinician to decide for eradication or not, in the rest. Local arrangements made for lab to send copy of all hospital initiated Hp+ve results to SpN for above action.

Introduction Previous studies have demonstrated that certain subgroups of patients have a worse prognosis following gastrostomy insertion (e.g., Dementia). However, these studies have often been retrospective and sample sizes have been small. We wished to examine survival following gastrostomy insertion with particular reference to the referral indication. Methods Gastrostomy insertions were examined from six hospitals in South Yorkshire and Derbyshire between January 2004 and September 2010. Data was collected prospectively from two centres (n = 1004) and from four centres retrospectively (n = 679). Age, gender, referral indication, comorbidity, biochemical profile and whether they were alive at 30 days was recorded for each case. Referral indication was divided into five subcategories; dysphagic stroke, neurological, nasopharyngeal cancer, cognitive impairment and other. Analysis for factors associated with death at 30 days was performed. Results 1651 patients were included in the study and the lowest 30-day mortality was found in the nasopharyngeal cancer cohort at 36/568 (6.3%). With respect to the other referral indications, 30-day mortality was 2/14 (14.3%, OR 2.5, 0.5–11.4, p = ns) in cognitive impairment, 91/488 (18.6%, OR 3.4, 2.3–5.1, p < 0.001) in dysphagic stroke, 36/324 (11.1%, OR 1.8, 1.1–3.0, p = 0.012) in neurological disease and 28/257 (10.9%, OR1.8, 1.1–3.0, p = 0.024) in the other category. Mortality at 30 days was also associated with increasing age >60 (OR 3.1, 2.1–4.6, p < 0.001), reducing serum albumin (p < 0.001), cardiac comorbidity (OR 2.1, 1.3–3.4, p = 0.0023), renal comorbidity (OR 2.1, 1.3–3.4, p = 0.004) and intercurrent infection (OR 3.0, 1.7–5.1, p < 0.001). At multivariate analysis only age and albumin were independent predictors of death at 30 days (both p < 0.01). Conclusion This is the largest UK dataset to assess outcomes following gastrostomy insertion. Indication for gastrostomy does have a bearing on mortality at 30 days with the lowest rates being found in patients with nasopharyngeal cancer. Our observations regarding mortality in these subgroups may be informative for clinicians, patients and relatives when making decisions around gastrostomy insertion.

Introduction There is a significant mortality associated with PEG. The Sheffield Gastrostomy Score (SGS) was devised to try and improve outcomes following this procedure by predicting 30-day mortality. After prospectively collecting demographic, biochemical and outcome data from a cohort of patients having a new PEG inserted (Hospital A, n = 403), multivariate analysis identified that age and albumin were determinants of 30-day mortality (p < 0.001). Age and albumin were attributed scores in a scoring system, the SGS, with age scoring 0 or 1 (<65/≤65 years) and albumin scoring 0, 1 or 2 (>35, 25–34 and <25 g/L). Composite scores in the SGS of 0 to 3 corresponded to 30-day mortalities of 0%, 7%, 21.3% and 37.3%, respectively. The SGS was then validated on a separate cohort of patients from a second hospital in Sheffield, from within the same trust (Internal validation: Hospital B, n = 153) with comparable 30-day mortality figures. Thus our aim was to externally validate the SGS (outside of Sheffield) and determine its potential application to a wider population. Methods Four local district general hospitals were used to externally validate the SGS. Demographic, biochemical and outcome data was obtained from all patients undergoing PEG insertion between June 2006 and June 2009. χ2 analysis was used to compare actual 30-day mortality rates in the external cohort to the rate predicted by the SGS. Results A total of 679 new PEGs were inserted during this period in these four hospitals. Complete records were obtained from 88% (597/679) and analysed (median age 71, 322 male). The 30-day mortality for this external validation cohort was 13.6%. The main indications for PEG insertion were stroke (33.7%), oropharyngeal malignancy (32.3%) and neurodegenerative diseases (17.4%). Univariate analysis predictors of 30-day mortality in this external cohort were: increasing age, low serum albumin and stroke. There were no significant differences between the observed and the predicted mortality (p ≤ 0.05) in the external validation cohort using the SGS. Conclusion Our results suggest that the SGS can accurately stratify patients into different risk categories, with higher scores correlating with significantly lower survival. We feel that the SGS could have an important role in those patients where the benefits and risks of gastrostomy are unclear. Table 1 OC-033 PEG score in internal and external validation cohort Score Predicted 30 day mortality Hospital A Internal validation cohort Hospital B Observed mortality (p value) External validation cohort Observed mortality (p value) 0 0% 0% (1) 3.2% (0.57) 1 7% 7.7% (1) 10.1% (0.42) 2 21.30% 15.2% (0.41) 20.3% (0.88) 3 37.30% 29.3% (0.51) 31.6% (0.66)

Introduction Faecal calprotectin (FC) is a protein complex released from degraded neutrophils exuded through the gut wall into the lumen. Its levels are therefore likely to better reflect the presence and intensity of gut inflammation than our conventional inflammatory markers: C reactive protein (most commonly used by us), platelets, albumin, endoscopy, histopathology and imaging. FC values (mg/kg) suggest inflammatory status as <50:Nil; 50–100: possible; >100: likely; >1000: definite. The factors limiting its routine use include need for spot stool collection, which many patients dislike and the time involved for manual assay, hence higher cost. Is the ‘help’ in decision making worth the effort and cost? Aim To test the utility of FC in the routine clinical setting of a gastroenterology unit in a UK DGH. Methods Retrospective study of consecutive new and follow up patients who had FC (PhiCal ELISA test) done in our clinics between 10/2007 and 2/2009 (n = 200). Patients were categorised into IBD-flare (relapse), IBD-active (persistent activity), IBD-remission and non-IBD (eg, IBS, abdominal pain, weight loss). The spot FC values are tabulated as median and range according to presence or absence of inflammation by conventional markers as above (≤ 1 test done within 2 weeks in majority). Results See table 1. Conclusion FC levels > 500 correlate well with flare and active IBD. Very low levels (< 7.8) reliably indicate lack of significant GI inflammation. Levels > 7.8 in non-IBD patients (majority of new referrals) may indicate ongoing GI inflammation in a few and hence the need to investigate fully rather than assume functional GI disease as the FC levels are within the published “normal” range. Raised FC in IBD-remission may signify ongoing silent inflammation with potentially significant influence on long-term prognosis (an area to be explored). Discussion This retrospective pilot study in our unit suggests that the effort and cost of FC is exceeded by the help it offers. It is of definite help when levels are very high or very low. We need to assess systematically the disease correlation with moderate FC elevation to develop local normal values.

chemiluminescence immunoassays.Hepatic expression levels of cathelicidin (Camp) were determined by qPCR (TaqMan).Results: BALB-Abcb4 -/-mice showed significant increases in liver enzymes activities (ALT, AP) as compared to wild-type controls.Of note, bone mineral content and bone content were significantly (p < 0.05) reduced in male (492±24 vs. 347±35 mg) and female knockout mice (1.65±0.06 vs. 1.31±0.13%),respectively.Plasma calcium levels were decreased (p < 0.01), whereas inorganic phosphorus was increased (p < 0.001), consistent with lower 25OHvitamin D 3 levels in BALB-Abcb4 -/-mice (males 30.5±6.3 vs. 56.4±4.2, females 33.9±7.8 vs. 60.4±3.8;p < 0.008).Of note, hepatic expression of the antimicrobial peptide cathelicidin, which is induced by vitamin D, was markedly increased in Abcb4 deficient mice as compared to controls.Conclusions: BALB-Abcb4 knockout mice on a vitamin D-containing diet display alterations of calcium homeostasis and bone mineralisation.These effects can be attributed, at least in part, to vitamin D deficiency.We speculate that therapeutic interventions correcting low vitamin D levels also affect local and systemic inflammation in BALB-Abcb4 knockout mice, all of which contribute to hepatic osteodystrophy in patients with chronic cholestasis as well.

Introduction A link between steatosis and Prednisolone therapy has been suggested, but is poorly documented. In chronic hepatitis C, steatosis has been linked with fibrosis progression. The prevalence and significance of steatosis in autoimmune hepatitis (AIH) are unclear. Methods To assess the prevalence, progression and possible significance of steatosis in AIH. We studied 99 patients with AIH, 17 men, median age 48 (9–85) years, 31 probable, 68 definite by IAIHG criteria. We assessed steatosis (grade 1–3 and distribution), Ishak necro-inflammatory (NI) score and Ishak fibrosis score in paired liver biopsies: the initial diagnostic biopsy and a follow-up biopsy when in remission after median 25 (3–115) months Prednisolone. Results 24 of the 99 patients had steatosis on the diagnostic biopsy (16 grade 1, 8 grade 2): 8 zone 1, 6 zone 2 and 12 zone 3. Patients with steatosis had lower NI scores than those without, (median 8 vs 13: p=0.003) but a similar prevalence of plasma cells (54.2% vs 64%) and rosettes (62.5% vs 60%). They were older (median 59 vs 45 years, p=0.001) and had a higher prevalence of diabetes (42% vs 12%, p=0.012) than those without steatosis but had similar body weight and BMI values. On follow-up biopsy, 46 of the 99 patients had steatosis, which had appeared or worsened in 31 patients. In six patients steatosis disappeared and 26 patients had developed new steatosis (7 zone 1, 6 zone 2, 24 zone 3). Steatosis grade worsened between diagnostic and follow-up biopsy (p<0.001). Worsening of steatosis was not related to gender, age, diabetes, or body weight or to duration, initial dose or maintenance dose of Prednisolone. Patients with worsening steatosis, compared to those with stable or improved steatosis, had similar falls in median NI score (12 to 3 and 13 to 3: p<0.001) between diagnostic and follow-up biopsy. However, they achieved no improvement in median fibrosis stage (3 to 3: NS), whereas in patients with stable or improving steatosis, median fibrosis score fell from 3 to 2 (p=0.004). In regression analysis worsening of steatosis was significantly associated with severity of fibrosis on follow-up biopsy: p=0.039. Conclusion Steatosis is found in 1/4 of patients with AIH and is related to age and diabetes. Steatosis worsens in 1/3 of patients treated with Prednisolone, although an association with dose or duration of Prednisolone was not observed. Patients with worsening steatosis, despite reduction in inflammation, fail to achieve improvement in fibrosis, suggesting that steatosis progression might compromise long-term outcome in AIH.

Introduction All patients diagnosed with gastro-oesophageal reflux disease (GERD) in our DGH over the last 3 decades have been systematically followed up. We present the outcome of BE cohort diagnosed 1977–2006 and followed until 31.10.2009, set against the numbers of newly diagnosed GERD. Methods BE was diagnosed visually and confirmed by histology in about 90%. Follow-up (FU) was by surveillance endoscopy+biopsy in the fit or clinically (clinic visit/telephone survey) with endoscopy reserved for alarm symptoms in the others. The GI database closed for non-BE GERD 31.12.2001 but continues for BE. Results BE and GERD 1977-2001 Comparison 1. Incidence (Abstract 071): Both GERD and BE rose in successive 5-year periods. 2. Demography: BE patients were a decade older than reflux patients (mean age at presentation 62 vs 52 years); both had a slight male preponderance (BE 62%, GERD 55%). 3. Complications: Presentation with complications was more common in BE patients (haemorrhage and/or anaemia 10% vs 5%, stricture 10% vs 2%). 4. Mortality. BE 316/752 (42%), GERD 2799/11 622 (24%), mean FU 6 years, range 0–31. BE 1977-2009 Natural history. 1. Numbers continued to rise, 364 diagnosed in the final 5 years (2002-06), totalling 1116. 2. Oesophageal adenocarcinoma (EAC). 53 who presented with or developed EAC within 1 year are excluded as prevalent cancers. Outcome: The remaining 1063 BE had total FU of 6885 patient-years (mean 6.5 years range 0–31) during which 42 (4%) developed EAC, that is, 1 tumour per 164 patient-years of FU. The mean time from diagnosis of BE to EAC was 9 years (range 13 months–24.4 years) occurring at a mean age of 71 years (range 50–86). 3. Mortality: 320/1063 (30%) died during follow-up, 27 (2.5%) from EAC, 54 (5%) from other tumours, the remaining 239 (22%) mainly from cardio-vascular and respiratory causes. 4. Surveillance group, development of EAC, potentially curative resection and outcome. Endoscopic FU: EAC n=26; resection 12; 6/12 died from tumour. Clinical FU: EAC n=11; resection 4; all 4 died from tumour. No FU: EAC n=5; resection 1, still alive. Abstract PWE-071 Incidence of newly diagnosed GERD and Barrett's 1977–2001* 1977–1981 1982–1986 1987-1991 1992–1996 1997–2001 Total All GERD 714 1587 2381 3812 3880 12 374 Barrett's
 n (%) 48 (6.7) 65 (4.1) 156 (6.6) 190 (5) 293 (7.6) 752 (6.1) * Note: GERD non-Barrett's database closed end 2001. Barrett's 2002–2006 n=364. Conclusions (1). During BE follow-up 4% developed EAC. (2) 8% of BE deaths were from EAC but the vast majority from other causes, perhaps reflecting their older age. (3) Surveillance. The rising prevalence of BE and increasing use of endoscopic therapy for early cancer in those unfit for resection has nevertheless strengthened the case for surveillance.

POSTERSreceptors.INT-767 does not show cytotoxic effects in HepG2 cells, does not inhibit cytochrome P450 enzymes, is highly stable to phase I and II enzymatic modifications, and does not inhibit the human ERG potassium channel.In line with its dual activity, INT-767 induces FXR-dependent lipid uptake by adipocytes, with the beneficial effect of shuttling lipids from central to peripheral storage, and promotes TGR5-dependent GLP-1 secretion by enteroendocrine cells, a validated target in the treatment of type 2 diabetes.Conclusions: Collectively, these preclinical results indicate that INT-767 is a selective bile acid-derived agonist able to modulate effectively both FXR and TGR5-dependent pathways, suggesting potential clinical applications in the treatment of liver and metabolic diseases.

Introduction All patients diagnosed with gastro-oesophageal reflux disease (GERD) in our DGH over the last 3 decades have been systematically followed up. We present the outcome of BE cohort diagnosed 1977–2006 and followed until 31.10.2009, set against the numbers of newly diagnosed GERD. Methods BE was diagnosed visually and confirmed by histology in about 90%. Follow-up (FU) was by surveillance endoscopy+biopsy in the fit or clinically (clinic visit/telephone survey) with endoscopy reserved for alarm symptoms in the others. The GI database closed for non-BE GERD 31.12.2001 but continues for BE. Results BE and GERD 1977-2001 Comparison 1. Incidence (Abstract 071): Both GERD and BE rose in successive 5-year periods. 2. Demography: BE patients were a decade older than reflux patients (mean age at presentation 62 vs 52 years); both had a slight male preponderance (BE 62%, GERD 55%). 3. Complications: Presentation with complications was more common in BE patients (haemorrhage and/or anaemia 10% vs 5%, stricture 10% vs 2%). 4. Mortality. BE 316/752 (42%), GERD 2799/11 622 (24%), mean FU 6 years, range 0–31. BE 1977-2009 Natural history. 1. Numbers continued to rise, 364 diagnosed in the final 5 years (2002-06), totalling 1116. 2. Oesophageal adenocarcinoma (EAC). 53 who presented with or developed EAC within 1 year are excluded as prevalent cancers. Outcome: The remaining 1063 BE had total FU of 6885 patient-years (mean 6.5 years range 0–31) during which 42 (4%) developed EAC, that is, 1 tumour per 164 patient-years of FU. The mean time from diagnosis of BE to EAC was 9 years (range 13 months–24.4 years) occurring at a mean age of 71 years (range 50–86). 3. Mortality: 320/1063 (30%) died during follow-up, 27 (2.5%) from EAC, 54 (5%) from other tumours, the remaining 239 (22%) mainly from cardio-vascular and respiratory causes. 4. Surveillance group, development of EAC, potentially curative resection and outcome. Endoscopic FU: EAC n=26; resection 12; 6/12 died from tumour. Clinical FU: EAC n=11; resection 4; all 4 died from tumour. No FU: EAC n=5; resection 1, still alive. Conclusions (1). During BE follow-up 4% developed EAC. (2) 8% of BE deaths were from EAC but the vast majority from other causes, perhaps reflecting their older age. (3) Surveillance. The rising prevalence of BE and increasing use of endoscopic therapy for early cancer in those unfit for resection has nevertheless strengthened the case for surveillance.

Introduction We have previously1 reported presence of persisting necro-inflammation (Ishak score (NIS) >3), despite biochemical remission, in 38% of AIH patients; this was independently associated with mortality. Aim We aimed here to assess outcome further in these patients and to identify demographic, disease and treatment-related factors associated with death or for liver transplantation (OLT). Patients and Methods 50 patients with AIH by IAIHG criteria (16 probable, 34 definite, 39 women, median age 52 years), who had achieved biochemical remission (ALT<2× upper normal limit, median (range) 29 U/l (9–84)) for 1 (0.5–5.5) years on immunosupression (IS) treatment, but had NIS >3 on remission biopsy (performed 2.1 (1–14) years, following diagnostic biopsy. After remission biopsy, 30 patients were given routine IS (Prednisolone withdrawal plus increased Azathioprine to 2 mg/kg BW/day) and 20 received altered/enhanced IS (increased Azathioprine with continuation of Prednisolone (n=11) or change to another IS drug n=9). Results 16 patients died, six due to liver disease (2 HCC, 3 liver failure, 1 portal vein thrombosis). 2/6 died post OLT. 10- and 20-year mortality was 11+6% and 65+11% (all cause death/OLT) and 5+4% and 32+12 (liver related death/OLT). 11 patients had cirrhosis at diagnosis; in the remainder, de-novo cirrhosis development rate was 37+12% after 10 years. In Cox regression analysis, all-cause death/OLT was associated with older age (p=0.029) but with no other parameter, including NIS or fibrosis on follow-up biopsy, whether subsequently given routine or altered/enhanced IS, or whether or not Prednisolone was continued. Likewise, no parameters were associated with liver-related death/OLT. 18 patients underwent further remission biopsy 2.3 (1–5.5) years later. NIS fell slightly, compared to first remission biopsy (median 5 to 4 p=0.011) and fell to <3 in eight patients, all of whom survived. Fibrosis stage was unchanged (median 3 to 3). Conclusion Persistent necroinflammation in AIH is associated with substantial mortality. However (apart from age) we could not identify predictors of mortality and specifically, could not relate outcome to alterations in IS. More intensive IS strategies may be required for these patients.

April 25 cells increases greatly following hepatic injury.The present study was aimed to provide data to support this hypothesis in humans.Methods: The study included 219 consecutive patients (154 males), median age 55 years (range, 22-68), who underwent liver transplantation for end stage liver disease; 236 blood donors (164 males), served as controls.Genotyping for the IL-6 -174 G>C polymorphism, that is associated with high IL-6 production, was performed on whole blood samples by a PCRrestriction fragment length polymorphism assay.All total hepatectomy specimens were sectioned at intervals of approximately 1 cm in search for suspicious focal hepatic lesions.Results: HCC foci were identified in the native livers of 66/219 patients undergoing liver transplantation.IL-6 -174 G>C allelic frequencies in patients and controls were G = 0.650 and 0.689, C = 0.350 and 0.311, respectively (p = ns).In both groups, no departure from the Hardy-Weinberg distribution was observed for each allele.A higher prevalence of the G/G + G/C genotypes was detected in patients with HCC (65/66) in comparison to the remaining patients without HCC (135/153) (p < 0.02).A highly significant linear trend was observed for increasing frequencies of HCC stratifying the patients as follows: males and females carrying the IL6 -174 C/C genotype (1/19), female patients with the G/G + G/C genotypes (9/60) and finally male patients with the G/G + G/C genotypes (56/140) (p < 0.0001).At multivariate analysis, detection of HCC foci in the explanted liver was independently associated with age at operation >50 years (p < 0.001), male gender (p = 0.001) and carriage of the IL-6 high producer genotypes (-174 G/G + G/C) (p = 0.001).Conclusions: The IL6 -174 G>C polymorphism may play a role in HCC development among patients with end stage liver disease.The protective effect of female gender against the occurrence of liver cancer is mainly effective among carriers of high IL-6 producer (IL6 -174 G/G + G/C) phenotype.