Genetic and environmental factors are involved in the pathogenesis of inflammatory bowel diseases (IBD). The study aimed at investigating the potential influence of single nucleotide polymorphisms (SNPs) NOD2 rs2066844, NOD2 rs2066845, NOD2 rs2066847, IL23R rs11209026, PTPN2 rs2542151, PTPN2 rs7234029, and ATG16L1 rs2241880 on the response to immunomodulatory therapies and disease course in Crohn’s disease (CD). This is an uncontrolled retrospective monocentric study including patients from the IBD outpatient clinic of Heidelberg University Hospital. Therapy responses and disease courses were related to genetic findings. 379 patients with CD were included. The presence of at least one PTPN2 rs7234029 risk allele was associated with nonresponse to anti-interleukin-12/23 treatment (89.9% vs. 67.6%, p = 0.005). The NOD2 rs2066844 risk allele was associated with a first-degree family history of colon cancer (12.7% vs. 4.7%, p = 0.02), the ATG16L1 rs2241880 risk allele with ileal CD manifestation (p = 0.027), and the IL23R rs11209026 risk allele with a higher rate of CD-related surgeries per disease year (0.08 vs. 0.02, p = 0.025). The results of this study underline the relevance of genetic influences in CD. The association of the PTPN2 rs7234029 risk allele with nonresponse to anti-interleukin-12/23 treatment in CD patients is a novel finding and requires further investigation.

Acute hepatitis E virus infection may cause mild, self-limiting hepatitis, either as epidemic outbreaks or sporadic cases, the latter of which have been reported in industrialized countries. Chronic infections are uncommon and have been reported in immunosuppressed patients, patients with human immunodeficiency virus infection, and patients with hematological malignancies.

To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis (PSC) and secondary sclerosing cholangitis (SSC). Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were analyzed. Fourteen of these patients were diagnosed with PSC, 10 with SSC, 11 with choledocholithiasis or no identifiable biliary disease, and 6 with cholangiocellular carcinoma (CCC). Bile acid, cholesterol, protein, and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical methods. Phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) species were quantified using nano-electrospray ionization tandem mass spectrometry. Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition, with only minor statistical differences. Total biliary PC concentrations were highest in controls (8030 ± 1843 μmol/L) and lowest in patients with CCC (1969 ± 981 μmol/L) (P = 0.005, controls vs SSC and CCC, respectively, P < 0.05). LPC contents in bile were overall low (4.2% ± 1.8%). Biliary LPC/PC ratios and ratios of biliary PC to bilirubin, PC to cholesterol, PC to protein, and PC to bile acids showed no intergroup differences. PC and LPC profiles being similar in patients with or without sclerosing cholangitis, these phospholipids are likely not of major pathogenetic importance in this disease group.

Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a life-threatening medical condition requiring hospitalization and often colectomy. Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases (IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated. To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis. We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects. In the majority of the 22 included patients (68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d (mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4% were discharged from the hospital under continued oral tacrolimus therapy. In 36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment (mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%, respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects. The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroid-refractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.