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Primary sclerosing cholangitis (PSC) is an inflammatory disease of the biliary tree, characterised by stricturing bile duct disease and progression to liver fibrosis. The pathophysiology of PSC is still unknown. The concurrence with inflammatory bowel disease (IBD) in about 70% of cases has led to the hypothesis that gut-homing lymphocytes aberrantly traffic to the liver, contributing to disease pathogenesis in patients with both PSC and IBD (PSC-IBD). The discovery of mutual trafficking pathways of lymphocytes to target tissues, and expression of gut-specific adhesion molecules and chemokines in the liver has pointed in this direction. There is now increasing interest in using drugs that intervene with these trafficking pathways (e.g. vedolizumab, etrolizumab) for the treatment of PSC-IBD. In this review we discuss what is currently known about the immunological interactions between the gut and the liver in concomitant PSC and IBD, as well as potential therapeutic options for intervening in these mechanisms.

BACKGROUND & AIMS: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. METHODS: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). RESULTS: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1-12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1-81.2) among UDCA-treated patients and 60.7% (95% CI 58.2-63.4) among untreated patients (p

MAIN RECOMMENDATIONS 1 ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic resonance cholangiography (MRC) should be preferred over endoscopic retrograde cholangiopancreatography (ERCP).Moderate quality evidence, strong recommendation. 2 ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is equivocal or contraindicated in patients with persisting clinical suspicion of PSC. The risks of ERCP have to be weighed against the potential benefit with regard to surveillance and treatment recommendations.Low quality evidence, weak recommendation. 6 ESGE/EASL suggest that, in patients with an established diagnosis of PSC, MRC should be considered before therapeutic ERCP.Weak recommendation, low quality evidence. 7 ESGE/EASL suggest performing endoscopic treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies) of suspected significant strictures identified at MRC in PSC patients who present with symptoms likely to improve following endoscopic treatment.Strong recommendation, low quality evidence. 9 ESGE/EASL recommend weighing the anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a case-by-case basis.Strong recommendation, moderate quality evidence.Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation.Strong recommendation, low quality evidence. 16 ESGE/EASL suggest routine administration of prophylactic antibiotics before ERCP in patients with PSC.Strong recommendation, low quality evidence. 17 EASL/ESGE recommend that cholangiocarcinoma (CCA) should be suspected in any patient with worsening cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant stricture, particularly with an associated enhancing mass lesion.Strong recommendation, moderate quality evidence. 19 ESGE/EASL recommend ductal sampling (brush cytology, endobiliary biopsies) as part of the initial investigation for the diagnosis and staging of suspected CCA in patients with PSC.Strong recommendation, high quality evidence.

Objective: Studies on the epidemiology of primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) show variable outcome. We aimed at systematically reviewing the incidence and prevalence rates, as well as geographical distribution and temporal trends of PSC and PBC. Data sources: A systematic search of literature was performed in Medline and EMBASE (search last conducted January 10th, 2011). Study selection: Population-based epidemiological studies reporting incidence and/or prevalence rates for PSC or PBC in a defined geographical area of at least 100,000 adult inhabitants were considered relevant. Data extraction: Study area, study period, number of patients, number of inhabitants, incidence per 100,000 inhabitants per year, prevalence per 100,000 inhabitants, method of case-finding, method of case-ascertainment, male/female ratio and in case of PSC, occurrence of inflammatory bowel diseases (IBD) were extracted from retrieved articles. Results: The literature search yielded 2286 abstracts of which 31 articles fulfilled all inclusion criteria. Studies varied in size from 10 to 770 patients in catchment areas from 100,312 to 19,230,000 inhabitants. The incidence and prevalence rates for PSC range from 0 to 1.3 per 100,000 inhabitants/year and 0-16.2 per 100,000 inhabitants, respectively. PBC incidence rates range from 0.33 to 5.8 per 100,000 inhabitants/year and prevalence rates range from 1.91 to 40.2 per 100,000 inhabitants; prevalence rates are increasing in time. Conclusions: Incidence and prevalence rates of both PSC and PBC vary widely and seem to be increasing. True population-based studies are scarce and therefore large population-based studies combining meticulous case-finding and case-ascertainment strategies are necessary. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Background & Aims Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. At present, there is no appropriate histologic scoring system available for PSC, evaluating both degree of necroinflammatory activity (grade) and fibrosis (stage). The aim of this study was to assess if three scoring systems, commonly used in different liver diseases could be applied for grading and/or staging of PSC. Methods Sixty-four PSC patients from a Dutch cohort, who underwent diagnostic liver biopsy, were included. Staging was scored using Ishak, Nakanuma, and Ludwig systems. Grading was scored using Ishak and Nakanuma systems. Three measures of outcome were defined; transplant-free survival, time to liver transplantation (LTx) and occurrence of cirrhosis related symptoms (CRS). Association of grade and stage with outcome was estimated using Kaplan–Meier log-rank test, and Cox regression analysis. Correlation with biochemistry was assessed by Spearman's rank test. Results There were strong associations between disease stage measured by Ishak, Nakanuma, and Ludwig staging systems with both outcome measuring transplant-free survival (Hazard ratio (HR) 2.56; 95% CI 1.11–5.89, HR 6.53; 95% CI 2.01–21.22, HR 1.94; 95% CI 1.00–3.79, respectively), and time to LTx (HR 4.18; 95%CI 1.51–11.56, HR 7.05; 95% CI 1.77–28.11, HR 3.13; 95%CI 1.42–6.87, respectively). Ishak and Nakanuma grading systems were not associated with CRS. Weak correlations between histopathology and liver biochemistry were shown. Conclusion Applying the Nakanuma, Ishak, and Ludwig histopathological staging systems is feasible and clinically relevant given their association with transplant-free survival and time to LTx. This suggests that these staging systems could be likely candidates for surrogate endpoints and stratification purposes in clinical trials in PSC.

G A A b st ra ct s age 65. Data were extracted from a comprehensive electronic medical record based on ICD9 coding and indexed terms. Results: There were 58 geriatric UC patients identified who underwent surgery. These patients had a mean age of 72 ± 5.6 years (range 65-87 years: males 34: females: 24). Mean duration of UC was 0-50 years (mean 9 ± 12 years SD). The majority of geriatric UC patients (79.3%; n=46) were diagnosed with UC after age 65 years, while 20.6% (n=12) had been diagnosed with UC before age 65. Patient demographics included 89.7% white, 1.7% African American and 8.6% unknown race. Among operative UC patients, 29.3% were positive for Clostridium difficile (C Diff) infection at the time of surgery. Colon carcinoma was noted in 22.4% of the geriatric UC operations. Patterns of bowel surgeries in the geriatric UC cohort included: Proctocolectomywith ileostomy (60.6%); hemicolectomy (14%), Ileocolectomy/partial colectomy (12.7%). Colectomy with Ileal pouch-anal anastomosis (6.6%); Hartmann closure with colostomy (6.1%). Operative mortality in the geriatric UC patients was 5% during the surgical admission. Length of stay for the UC surgery admissions was 10.9 ± 11.4 days(SD). Conclusion: Our study demonstrates that C Diff infection or colon cancer was associated with majority of geriatric UC operations. Operative mortality was significant, occurring in 5% of patients. A majority of geriatric UC patients requiring surgery demonstrated new onset disease, suggesting a more aggressive phenotype tends to present in the elderly age group.

Background and aims: PSC-IBD is reported to represent a distinct phenotype of IBD characterized by colitis, rectal sparing and backwash ileitis, but this has so far not been confirmed in large well-phenotyped cohorts. The aim of this study was to assess the IBD phenotype associated with PSC in a large Dutch PSC cohort using endoscopic and histopathological criteria. Methods: PSC cases were identified and ascertained, fulfilling well-established serological, histological and radiological criteria in 30 hospitals in The Netherlands. IBD location was recorded according to the Montreal classification. To assess the occurrence of backwash ileitis a subgroup analysis was performed in 40 cases and 80 ageand sex-matched IBD controls with at least one complete ileocolonoscopy including terminal ileum histology, reviewing 370 endoscopy and pathology reports written between 2001 and 2010. Results: 324 (64%) of a total of 506 PSC patients had coexistent IBD, mainly ulcerative colitis (UC, 72%). 147 (80%) of the PSC-UC patients had a pancolitis, 28 (15%) a left sided colitis and eight (4%) a proctitis. Sixty (95%) PSC-Crohn's disease (CD) patients had an (ileo)colitis and three ileitis only (5%). In the subgroup analysis of 40 PSC-IBD patients twenty-seven (68%) PSC-UC patients were identified, as well as twelve (30%) PSC-CD patients and one (2%) PSC-undetermined IBD patient. Twenty-five (93%) PSC-UC patients had a pancolitis, compared to thirty-three (61%) matched UC patients (p = 0.034). Left sided colitis was seen in seventeen (32%) UC controls and in none of the PSC-UC patients (p = 0.001). Backwash ileitis was seen in only one (4%) PSC-UC patient and in none of the UC controls. Conclusion: PSC-IBD represents a distinct IBD phenotype. The majority of Dutch PSC-UC patients have a pancolitis. In case of PSC-CD, colonic inflammation is involved in 95% of patients. Backwash ileitis is not a prominent finding in Dutch PSC-UC cases.