D. Caroli

Clinical Course and Outcome of Autoimmune Hepatitis/Primary Sclerosing Cholangitis Overlap Syndrome

Autoimmune hepatitis/primary sclerosing cholangitis (AIH/PSC) overlap syndrome is a relatively uncommon variant of PSC.AIM:To evaluate the natural history of AIH/PSC overlap syndrome compared to a group of “classical” PSC.METHODS:Forty-one consecutive PSC patients, with a regular follow-up of at least 2 years, were prospectively included in the study. Among these, 7 fulfilled the criteria for AIH/PSC overlap syndrome.RESULTS:The AIH/PSC overlap group significantly differed from the “classical” PSC group in the following parameters: mean age at presentation (21.4 ± 5.0 vs 32.3 ± 10 years, p < 0.01), AST 191.0 ± 14.8 vs 48.9 ± 34.5 U/L, p < 0.005), ALT (357.0 ± 26.5 vs 83.7 ± 60.7 U/L, p < 0.005) and serum IgG (25.6 ± 4.7 vs 12.9 ± 6.0 mg/dl, p < 0.0001). The mean follow-up was similar in the 2 groups (93.3 ± 65.9 vs 98.1 ± 65.9 months respectively). Treatment included immunosuppression + ursodeoxycholic acid (UDCA) in the AIH/PSC overlap patients, and UDCA in the “classical” PSC group. Deaths were recorded only in the classical PSC group. The median survival in the latter group was 207 months (95% C.I. 87.6-326.4). The major events during the follow-up included: OLTx (1/7 vs 6/34), and neoplasms (only in the group of “classical” PSC). The new Mayo score prognostic index only increased significantly during follow-up in the “classical” PSC group (r2 0.8117, p < 0.01)CONCLUSION:Patients with AIH/PSC overlap syndrome seem to benefit from immunosuppression + UDCA therapy, survival is apparently better than in “classical” PSC condition.

Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: Comparative analysis from two centers

The limited information and divergent results on the prevalence, incidence, and risk factors for hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) may be due to the low prevalence of the disease and geographical and environmental differences. Therefore, we analyzed the incidence, prevalence, survival, and risk factors for HCC in patients with PBC from two European centers (389 from Barcelona, Spain, and 327 from Padova, Italy) followed up for 9.3 ± 6.5 years. Gender, age, smoking habit, alcohol consumption, presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (anti‐HCV), and advanced histological stage (III‐IV) were evaluated as risk factors for tumor development. Twenty‐four patients (13 from Barcelona and 11 from Padova) developed HCC. The prevalence of HCC was similar in Barcelona (3.34%) and Padova (3.36%). The incidence was 0.35 and 0.37 per 100 patient‐years, respectively. Male gender, age >52 years, smoking habit, alcohol >40 g/day, HBsAg, and anti‐HCV were not associated with HCC. Advanced histological stage was the only factor associated with the development of HCC (odds ratio [OR]: 5.80, 95% confidence interval [CI]: 2.34‐14.38, P < 0.001). When analyzing the two series separately, male gender was associated with higher likelihood of HCC in Padova (OR: 8.09, 95% CI: 1.93‐33.8, P < 0.01). The median survival after the diagnosis of HCC was 36 months. Conclusion: The prevalence and incidence of HCC is similar in Spain and Italy and the advanced histological stage is the only risk factor associated with the development of HCC in PBC. The slight disparities observed between the two series might be explained by patient features on diagnosis of liver disease. (HEPATOLOGY 2009.)

A 35-year follow-up of a large cohort of patients with primary biliary cirrhosis seen at a single centre.

Background: The natural history of primary biliary cirrhosis (PBC) is still debated.

Plasma Adiponectin Levels in Primary Biliary Cirrhosis: A Novel Perspective for Link Between Hypercholesterolemia and Protection Against Atherosclerosis

INTRODUCTION:Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease.AIM:To investigate factors potentially preventing atherosclerosis in PBC patients.METHODS:Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-α) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 ± 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome.RESULTS:The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 ± 50.5 mg/dL in PBC vs 221.7 ± 39.7 mg/dL in NASH vs 209.8 ± 39.2 mg/dL in controls, P < 0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P < 0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase.CONCLUSIONS:The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.

Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis

Absract Aim: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. Methods: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. Results: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene). Conclusions: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.

Fatal hepatic decompensation in a bone marrow transplant recipient with HBV-related cirrhosis following lamivudine withdrawal

Lamivudine is a nucleoside analogue with a potent antiviral activity used as prophylaxis against hepatitis B virus reactivation in patients with chronic HBV infection receiving chemotherapy. No standard guidelines exist, however, for the duration of lamivudine treatment. We report a clinical case of a 56-year-old patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was treated with lamivudine for 1 year while receiving chemotherapy and a subsequent bone marrow transplant. Complete remission from multiple myeloma was achieved. Four months after lamivudine was withdrawn, he experienced HBV reactivation with jaundice, though no YMDD mutations were detected. The patient rapidly developed fatal decompensation with septicemia and renal failure. In conclusion, this case shows that physicians should avoid discontinuing nucleoside therapy in patients with HBV infection who undergo immunosuppression for concomitant neoplastic conditions.

Clean Colon Software Program (CCSP), Proposal of a standardized Method to quantify Colon Cleansing During Colonoscopy: Preliminary Results

Background and study aims: Neoplastic lesions can be missed during colonoscopy, especially when cleansing is inadequate. Bowel preparation scales have significant limitations and no objective and standardized method currently exists to establish colon cleanliness during colonoscopy. The aims of our study are to create a software algorithm that is able to analyze bowel cleansing during colonoscopies and to compare it to a validate bowel preparation scale. Patients and methods: A software application (the Clean Colon Software Program, CCSP) was developed. Fifty colonoscopies were carried out and video-recorded. Each video was divided into 3 segments: cecum-hepatic flexure (1st Segment), hepatic flexure-descending colon (2nd Segment) and rectosigmoid segment (3rd Segment). Each segment was recorded twice, both before and after careful cleansing of the intestinal wall. A score from 0 (dirty) to 3 (clean) was then assigned by CCSP. All the videos were also viewed by four endoscopists and colon cleansing was established using the Boston Bowel Preparation Scale. Interclass correlation coefficient was then calculated between the endoscopists and the software. Results: The cleansing score of the prelavage colonoscopies was 1.56 ± 0.52 and the postlavage one was 2,08 ± 0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ± 0.69) was dirtier than left colon segment prelavage (2.07 ± 0.71). The overall interobserver agreement between the average cleansing score for the 4 endoscopists and the software pre-cleansing was 0.87 (95 % CI, 0.84 – 0.90) and post-cleansing was 0.86 (95 % CI, 0.83 – 0.89). Conclusions: The software is able to discriminate clean from non-clean colon tracts with high significance and is comparable to endoscopist evaluation.

PWE-074 Hospitality discharge for alcohol related problems in north of italy: a sixteen – years period

Background and aims WHO (2014) estimates a remarkable decline in per capita pure alcohol consumption in Italy, dropped from 18.1 to 7.1 lt in the period 1970–2013. Despite this, Italian Report on Alcohol 2016 showed an increase in drinking outside meals and a rise in consumption and binge drinking among young people (18–24, 14–17), particularly in males. The impact of these drinking styles on hospitalisation is still under-researched. This study aims to evaluate the trends of hospitality discharge for alcohol-related liver disease in the period 2000–2016 in Veneto Region in North Eastern Italy (4.8 million inhabitants). Method Retrospective cohort analysis based on Veneto Region anonymous computerised database of hospital discharges between 2000 and 2016. All Veneto residents discharge records with principal diagnosis of alcohol-related liver disease (cod. ICD9-CM: 571.0, 571.1, 571.2, 571.3) were included in the study. The principal diagnosis was chosen as it is considered the primary reason for hospital admission. Standardised Hospitalisation Ratio (SHR) per five-year age group (ref. pop. Veneto 2008) was calculated and expressed per 100.000 population. Results Over the period 2000–2016, 28.968 hospital admissions for alcohol-related diseases were recorded. Most part of subjects were males (74%) with a SHR more than double compared to females (53.3 vs. 18; OR:2.96; CI 95%:2.89–3.04 p<0,05). The longitudinal analysis of the hospitalisation trend shows a 7% increase on average age in both sexes (from 58.8±9,2 to 62.6±9,6) and a substantial decrease of 66% in SHR (X2 trend: 3933,326). In the last year of observation SHR tends to 19.5, and the greater risk for males is confirmed (30.2 vs. 8.8; OR:3.51; CI 95%:3.05–4.10; p<0.05). Considering the age groups, the highest decline in SHR can be found in the ranges 45–64 (from 69.2 to 34.1) and >65 (from 69.3 to 26.8). Interestingly, SHR shows a slightly rising trend in the group 25–44 betweeen 2013 and 2016 (p<0.05). Conclusion In Veneto Region, the reduction in alcohol intake over the last 30 years has lead to a marked decrease in hospitalisation for alcohol-related diseases. However, the changes in drinking styles occurred in the age range 25–44 may explain the upward SHR trend between 2013 and 2016. Thus, in the next few years it is likely to expect an increase in hospitalisation in this age group. Public Health strategies are needed to address the new styles of alcohol consumption, especially in young people.Abstract PWE-074 Figure 1

PWE-008 Colorectal cancer screening programs and the rate of surgical oncology procedures in the veneto region (italy)

Introduction Colorectal cancer (CRC) is a leading cause of cancer mortality in the Veneto Region (North-east Italy). Population screening of adults between 50 and 75 for CRC was begun in 2002, and it became standard practice in all 21 local health units (LHU) of the region in 2008, 14 LHU provided in the program also follow-up colonoscopy and 7 LHU no. This study was carried out to evaluate the impact on surgery rates of CRC screening and follow-up programs. Method This is a retrospective cohort study on administrative data based on anonymous computerised database of Veneto Region hospital discharges between 2000 and 2015. All Veneto residents (in screening age) discharge records with principal diagnosis of CRC treated with surgery were included in the study. The number of patients studied rose approximately 18% reaching 1,547,097 for the last year (2015). The Standardised Hospitalisation Ratio (SHR) per five-year age group was calculated and expressed per 10 000 population. Results During the study period, 30 399 surgical procedures for colorectal cancer were performed (colon 63%, rectum 36%, secondary malignant neoplasm 1%) with a SHR of 139.1, higher in males (OR: 1.66; CI 95%: 1.62–1.7; p<0.05). An analysis of the annual SHR distribution uncovered two distinct phases: during the first phase there was a rising tendency that reached a maximum value in 2007 (166,9; X2 trend: 46.731; p<0.05) and during the second there was a falling tendency that reached its minimum value in 2015 (102.3; X2 trend: 429.791; p<0.05), with a total reduction of 28%. The cancer stratification by site shows that the rate of surgical procedures of the proximal colon during the last year was the same as the 2000 value (41.5), instead there was a significant decrease (−37,3%; X2 trend: 559.282; p<0.05) in the rate of procedures on the distal colon and rectum which fell from 94.4 to 59.2 (Figure1). The stratification of LHU in which the screening program included a follow-up colonoscopy and others didn’t show significant difference in the reduction in surgical procedures (Figure2). Abstract PWE008 Figure 1 Abstract PWE-008 Figure 2 Conclusion Study findings confirmed that CRC screening was effective in reducing the number of oncological surgical oncology procedures particularly with regard to the distal colon and rectum. Data analysis showed that the screening seemed to accelerate reaching the peak rate in surgical procedures that took place in 2007. After that time point the number of operations began to fall as far as the distal colon was concerned (it fell by 37.3%). Finally data suggest that the real benefit in reduction of oncological surgery procedures is due to the first screening colonoscopy. Disclosure of Interest None Declared

PWE-032 Fatty Liver Index (FLI), Which is An Accurate Predictor of Nonalcoholic Fatty Liver Disease (NAFLD), Is A Better Predictor of Cardiovascular Disease Risk in Type 2 Diabetic Patients than The UK Prospective Diabetes Study (UKPDS Risk Engine V 2.0)

Introduction NAFLD, which is increasingly and rapidly becoming the cause of liver disease in Western countries, is characterised by higher serum triglyceride and LDL levels, lower HDL levels, insulin resistance, and glucose intolerance, all crucial risk factors for the development of atherogenesis. The UK Prospective Diabetes Study (UKPDS risk engine v 2.0) and the Fatty liver index (FLI) are both validated prognostic scores for cardiovascular disease (CVD) risk and NAFLD in diabetic patients. Methods We retrospectively analysed 1902 patients attending our Diabetes Ambulatory in 2012–2013. The UKPDS risk engine and the FLI were calculated for each of these patient. Ninety-nine (19.2%) of these patients resulted at high CVD risk according to their UKPDS evaluation and underwent a complete CVD assessment (ergometric/ecostress test (EET), coronarography (CORO)). A two tailed t-test, Person’s Chi square test, and analysis of variance (ANOVA) were carried out. Results Sixty-six (59 M, mean age 68.1 y, mean disease duration 16.1 y, HbA1c > 7 prevalent) pts presented UKPDS positive/FLI > 60, 8/66 CORO+ (5 percutaneous transluminal coronary angiopathy-PTA, 3 cardiac bypass sugery-CABG, 1 peripheral transluminal angioplasty-PTA AAII) and 5 (4 M, mean age 68.6 y, mean duration disease 18.4 y, HbA1c > 7 prevalent) pts presented UKPDS positive/FLI < 20,1/5 CORO+ (1 PTCA; 1 CABG; 0 PTA, AII). In the light of this analysis, were able to pinpoint a FLI cutoff that is better able to identify, with respect to UKPDS, patients who will result positive at CORO (FLI > 52 detected 9/14 pts positive at CORO with p < 0.05). Ninety-nine pts UKPDS positive(EET negative 69.6% > 69/99) (100% > 14/14 CORO+) vs 81 pts FLI > 52 (EET negative 92.5% > 75/81) (64.2% > 9/14 CORO+). As expected, we found a significant association between CORO+ and FLI+ patients and microalbuminuria (p < 0.048), cholesterol (p < 0.020); triglycerides (p < 0.001), and LDL (p < 0.005). The only drug associated to CV risk was cardioaspirn (p < 0.003). Conclusion Study results demonstrate that FLI can be used as a marker to predict CVD risk in patients with FLI > 52. The number of patients who undergo CVD screening with a low percentage of positivity can thus be reduced. An early and aggressive treatment and monitoring program can instead be begun for type 2 diabetic patients with FLI > 52 and a reasonable suspicion of NAFLD because this population has higher risk of developing CVD events with respect to patients with FLI < 20. Disclosure of Interest None Declared