No description available.

Abstract Extraintestinal manifestations in inflammatory bowel disease (IBD) have been described with varying frequencies. The aim of this study was to estimate the prevalence of pancreatic duct abnormalities, exocrine and endocrine dysfunction, elevated pancreatic enzymes, hepato-biliary disease, coexisting cholangiographic and pancreatographic duct changes, and elevated serum levels of fibrosis markers in IBD, and to correlate the findings with clinical, endoscopic and histologic variables. From a local patient register, 237 patients were randomly selected and studied. Of these, 170 had ulcerative colitis (UC), 46 had Crohn's disease (CD), and 21 had indeterminate colitis (IC). A detailed history was obtained from medical records and in a face-to-face interview. The patients were screened with a para-aminobenzoic acid (PABA) test and, for pancreatic enzymes, liver function tests, serum aminoterminal propeptide of type III procollagen (PIIINP), and laminin. Further pancreatic evaluation included endoscopic retrograde cholangiopancreato-graphy (ERCP), ultrasound (US), secretin test, and glucagon C-peptide test. Further hepatobiliary evaluation consisted of ERCP, US, and liver biopsy. In IBD, the prevalence rates of pancreatic duct abnormalities and exocrine dysfunction were 8% and 4%, respectively. Parallel impairment of exocrine and endocrine functions was shown. Acute idiopathic pancreatitis may complicate IBD. About 7-17% presented with elevated pancreatic enzymes. Enzyme elevation was associated with extensive and histologically active disease and, in some cases, with primary sclerosing cholangitis (PSC). Abnormal liver test results were commoner in patients with CD than in patients with UC (30% versus 11%). The prevalence of PSC in IBD was 11%, which is higher than previously reported (3.7-7.5%). PSC was commoner in patients with CD than in patients with UC (17.4% versus 7.6%). About half of the PSC patients had concomitant pancreatic duct changes, and the prevalence of concurrent cholangiographic and pancreatographic duct changes in IBD was 4.6%. Both serum PIIINP and laminin were increased in IBD patients. This was not only seen in patients with hepatobiliary disease and PSC, but also in patients with pancreatic disease. In conclusion, pancreatic and hepatobiliary complications in IBD occur with high and similar frequencies in all IBD categories and are associated with each other. They are not clearly associated with the clinical course of IBD.

Diss. (sammanfattning) Stockholm : Karol. Inst., 2002. / Härtill 4 uppsatser.

JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley and Sons Australia, Ltd. Background and Aim: The United Kingdom-primary biliary cholangitis (UK-PBC) and global primary biliary cholangitis group (GLOBE) prognostic models have been recently developed to predict long-term outcomes in primary biliary cholangitis (PBC). However, these predictive scores have not yet been well evaluated in the U.S. population. Methods: We retrospectively reviewed newly diagnosed PBC patients at the Cleveland Clinic between November 1998 and February 2017. Adverse events were defined as liver transplantation, liver-related mortality, and all-cause mortality. Transplant-free survival (TFS) was estimated using the Kaplan–Meier method. Predictive performances of all prognostic models were evaluated using the C-statistic. Results: We identified 352 patients who used ursodeoxycholic acid therapy. Of them, 311 (88.4%) only had PBC, while 41 (11.6%) were diagnosed with PBC-autoimmune hepatitis overlap. A total of 22 (6%), 47 (13%), and 55 (16%) patients had adverse events within 5, 10, and 15 years after diagnosis, respectively. In patients with PBC only, the C-statistic in predicting 15-year adverse events was 0.75 per GLOBE compared to 0.74 per UK-PBC (P = 0.94), 0.73 per Rotterdam (P = 0.44), 0.66 per Barcelona (P = 0.004), 0.65 per Paris 1 (P = 0.005), 0.62 per Paris 2 (P < 0.0001), 0.60 per Toronto (P < 0.0001), and 0.60 per Mayo (P < 0.0001) scores. Median follow-up was 9.2 years. Ten-year TFS for patients who had optimal versus suboptimal treatment response was 92 versus 74% per Paris 1 (P < 0.0001), 95 versus 79% per Paris 2 (P = 0.0002), 93 versus 65% per Barcelona (P < 0.0001), and 96 versus 68% per Rotterdam (P < 0.0001) risk scores, respectively. Conclusion: In our cohort of PBC patients, the UK-PBC and GLOBE scores were both accurate and reasonably valid prognostic models in the U.S. population.

No description available.

Background: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) constitute rare chronic inflammatory biliary diseases which likely comprise genetic, environmental and autoimmune factors. Specific inhibitory (auto-) antibodies against the muscarinic acetylcholine receptor type 3 (mAChR3 auto-ab) may contribute to the pathogenesis of chronic biliary inflammation by modulating mAChR3− mediated signaling. Aims: The aim of this study was to analyze the prevalence and relevance of inhibitory mAChR3 auto-ab (mAChR3inh+ auto-ab) in a large cohort of PBC patients from two independent tertiary centers in Berlin and Leipzig in comparison to a large PSC cohort. Baseline parameters and response rates to standard treatment with ursodeoxycholic acid (UDCA) were characterized with respect to the individual mAChR3 auto-ab status. Methods: In total, the study population comprised 437 PBC patients, 187 PSC patients and 80 healthy controls. Clinical and laboratory baseline characteristics were retrieved from medical records. The response to ursodeoxycholic acid (UDCA) therapy after 12 months of treatment was available in 176 PBC and 45 PSC patients. Results: The prevalence of mAChR3inh+ auto-ab was significantly higher among PBC patients (11.2%, 49/437; p = 0.008 vs. healthy controls) and PSC patients (33.6%, 63/187; p < 0.0001 vs. healthy controls) compared to healthy controls (2.5%, 2/80), respectively. PBC patients with mAChR3inh+ auto-ab exhibited significantly higher levels of alkaline phosphatase (ALP) and bilirubin, which constitute established parameters for PBC risk stratification. Moreover, mAChR3inh+ PBC patients tended to show decreased response rates to UDCA therapy compared to PBC patients without mAChR3inh+ auto-ab (mAChR3− PBC). In contrast, PSC patients with mAChR3inh+ auto-ab showed no significant differences in laboratory findings compared to mAChR3 auto-ab negative (mAChR3−) PSC patients. Conclusion: MAChR3inh+ auto-ab might be involved in the pathogenesis and treatment response of chronic biliary inflammation in patients with PBC but not in patients with PSC.

No description available.

Inflammatory bowel disease (IBD) comprises diseases that are characterized by chronic or relapsing inflammation of the gastrointestinal tract. Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation in IBD. Immunoreactivity against an autoantigen that is expressed both in the gastrointestinal tract and the biliary tract could be the link between these diseases. A possible source of such an antigen is goblet cells. Immunostainings of normal human tissues using IBD patient sera showed goblet cell immunoreactivity against goblet cells in all parts of the gastrointestinal tract. The most frequent immunostaining was found against goblet cells in the appendix against which 84% (42/50) of IBD patients compared to 8% (4/50) of healthy blood donors showed immunoreactivity. To identify the corresponding antigen we used three different approaches, investigation of immunoreactivity to different candidate proteins compared to IBD sera, immunoscreening of an appendiceal cDNA library, and immunoprecipitation of protein lysates from mucin producing cells followed by SDS-PAGE and 2D gel electrophoresis. These approaches led to the identification of several candidate autoantigens of which complement C3 is the most promising. A novel staining pattern with strong immunoreactivity to granules and the apical membrane of biliary epithelial cells was identified with 35% (12/34) of PSC sera compared to none of healthy controls (n=28). Screening of a cDNA library from normal human choledochus identified PDZ domain containing 1 (Pdzk1) and Glutathion S transferase theta 1 (GSTT1) as potential candidates. Pdzk1 is an interesting candidate which is expressed in the intestinal tract and bile ducts. GSTT1 antibodies were not specific for PSC and are thought to develop as an alloimmune response in patients with the GSTT1-null genotype. In conclusion, we have identified specific immunoreactivity to goblet cells and biliary epithelial cells using sera from patients with IBD and PSC respectively. We have also identified several potential autoantigens.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Abstract Biliary carcinoma, biliary fistula with occasional gallstone ileus and primary sclerosing cholangitis (PSC) are serious diseases and present specific diagnostic and therapeutic challenges. Stenting of biliary obstruction has also involved problems, but the reports are contradictory and partly limited. The aim of the present work was to evaluate and compare various imaging modalities in biliary diseases. The study also aimed to evaluate the usefulness of metallic stents in malignant biliary obstruction. The study population consisted of 210 patients with gallbladder carcinoma, bile duct carcinoma, biliary fistula, PSC or malignant biliary obstruction and eight control patients with various hepatobiliary diseases. The imaging findings of 80 patients with gallbladder carcinoma, 58 patients with bile duct carcinoma, and 16 patients with biliary fistula were reviewed. Nine patients with PSC underwent magnetic resonance cholangiography (MRC) and magnetic resonance imaging (MRI) of the liver, ultrasonography (US) of the liver and the bile ducts and endoscopic retrograde cholangiography (ERC). Eight control patients had had MRC and MRI of the liver and ERC. The medical records and radiographs of 39 patients with malignant biliary obstruction treated with percutaneously inserted metallic stents were also analysed. The stents included 48 Wallstents and seven Memotherm stents. In cases of gallbladder carcinoma, US visualised the primary tumour in 68 % and computed tomography (CT) in 57 % of the cases examined, but both methods were insufficient for accurate staging. In bile duct carcinoma, US revealed the primary tumour in 63 % and CT in 44 % of the cases examined. Both methods were sensitive in diagnosing peripheral intrahepatic cholangiocarcinoma, but inaccurate for more distal bile duct carcinoma or abdominal spread. The infiltrating type of gallbladder carcinoma and bile duct carcinoma were difficult to detect. US and CT were sensitive in revealing bile duct obstruction. The patients with biliary fistula and gallstone ileus had undergone various examinations with pathological, but not diagnostic results, and there was often a delay to diagnosis. Imaging did not reveal any of the ten spontaneous fistulas, but CT showed one of the five cases of gallstone ileus, and Gastrografin® meal revealed the single case of Bouveret's syndrome. Fistulography or cholangiography revealed all but one of the six iatrogenic fistulas. A nonvisualised or shrunken gallbladder at US should raise a suspicion of biliary enteric fistula in an appropriate clinical setting. MRC-MRI depicted the changes of PSC correctly in nine patients (radiologist 1) and in eight patients with one false positive finding (radiologist 2) in a blinded analysis. In the segmental comparison MRC missed especially bile duct dilatations. MRC was too pessimistic in the evaluation of the predictors of poor outcome. US detected features suggestive of PSC in eight patients (radiologist 3). US was unable to indicate the predictors of poor outcome. Of the patients with metallic stents in malignant biliary obstruction, 30 % had early and 66 % late complications, including stent obstructions, which occurred in 27 % of the patients at a mean of 4.4 months. The cause was mostly tumour ingrowth or overgrowth. The 25-week and 50-week patency rates were 71 % and 42 %. The patency rates of the patients with cholangiocarcinoma were significantly the lowest. There was also a tendency towards lower patency with less dilatation of the stents, an increasing number of the stents, longer strictures and hilar strictures. Many other complications were infectious. 31 % of the patients had late reinterventions.