The role of the cytokine macrophage migration inhibitory factor (MIF) and its receptor, CD74, was assessed in autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Two MIF promoter polymorphisms, a functional -794 CATT5–8 microsatellite repeat (rs5844572) and a -173 G/C single nucleotide polymorphism (rs755622), were analyzed in DNA samples from over 500 patients with AIH, PBC, and controls. We found a higher frequency of the pro-inflammatory and high expression -794 CATT7 allele in AIH compared to PBC, while lower frequency was found in PBC compared to both AIH and healthy controls. MIF and soluble MIF receptor (CD74) were measured by ELISA in 165 serum samples of AIH, PBC, and controls. Circulating serum and hepatic MIF expression was elevated in patients with AIH and PBC vs. healthy controls. We also identified a truncated circulating form of the MIF receptor CD74 that is released from hepatic stellate cells and that binds MIF, neutralizing its signal transduction activity. Significantly higher levels of CD74 were found in patients with PBC vs. AIH and controls. Conclusions These data suggest a distinct genetic and immunopathogenic basis for AIH and PBC at the MIF locus. Circulating MIF and MIF receptor profiles distinguish PBC from the more inflammatory phenotype of AIH and may play a role in the pathogenesis and as biomarkers of these diseases.

BackgroundThere is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications.MethodsThis was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4‐month interval (October–December 2014) were eligible for inclusion. The primary outcome was the 30‐day major complication rate (Clavien–Dindo grade III–V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital‐level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.).ResultsOf 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30‐day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147).ConclusionOverweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.

Background: Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods: This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and intercentre variation in critical care admission after emergency laparotomy. Results: Of 4529 patients included, 37.8% (n¼1713) underwent planned critical care admissions from theatre. Some 3.1% (n¼86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n¼133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51e19.97) than planned admissions (OR: 2.32, 95% CI: 1.43e3.85). Some 26.7% of patients (n¼1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8e51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n¼10/145) of centres outside the 95% CI. Conclusions: After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

A 17-year-old girl presented with a history of elevated alkaline phosphatase and gamma-glutamyl transpeptidase (cGT) levels for several years. She was asymptomatic and did not have jaundice, pruritus, abdominal pain, nausea, vomiting, weight loss, rashes, or diarrhea. Viral hepatitis serologies, autoimmune serologies, and thyroid studies were all normal.She had a past medical history of anxiety, which was treated with Celexa. Otherwise, she was healthy and had no major childhood illnesses or history of substance abuse. She had traveled extensively with her family during her childhood, notably to Northern and Eastern Africa and Southeast Asia. Her physical examination was unremarkable. An abdominal ultrasound examination was performed, and the findings were normal. Magnetic resonance cholangiopancreatography (MRCP) showed mild beading of the intrahepatic ducts consistent with the diagnosis of primary sclerosing cholangitis involving the small ducts. The patient was started on ursodiol (300 mg three times per day), and her alkaline phosphatase and cGT levels promptly normalized.Subsequently, colonoscopy was performed to rule out concomitant inflammatory bowel disease. The mucosa appeared normal on endoscopic examination, but random biopsy samples were taken to rule out quiescent colitis. The pathology specimens revealed schistosoma eggs, and stool studies were positive for Schistosoma mansoni. Percutaneous liver biopsy was then performed to evaluate hepatic involvement. There were Fig. 1. Portal triad demonstrating an intravenular granuloma surrounding a schistosoma egg. Onion-skinning fibrosis impinging on small interlobular ducts can also be noted. The over all histological examination showed minimal portal fibrosis with focal areas of periportal extensions.

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