Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases:A cross-sectional and longitudinal analysis

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is common in the German population,with an even higher prevalence in inflammatory bowel disease patients.AIM To investigate the risk factors for NAFLD in inflammatory bowel disease patients.METHODS This monocentric retrospective study with a cross-sectional and a longitudinal part included 694 patients.Inclusion criteria were diagnosed inflammatory bowel disease,age≥18 years,availability of at least one abdominal ultrasound.Patients with infectious or suspected alcoholic fatty liver disease were excluded.NAFLD was defined by increased echogenicity at liver ultrasound.Demographic characteristics,disease activity and medications were analyzed as potential risk factors.Parameters influencing the course of NAFLD were identified by a generalized linear mixed model.RESULTS Forty-eight percent of Crohn’s disease(CD)patients and 44%of ulcerative colitis patients suffered from NAFLD.Its occurrence was associated with greater age,hypertension and body mass index(BMI)in both groups,and with higher disease activity and dyslipidemia in CD.2467 ultrasound results were included in the longitudinal analysis.Risk factors for NAFLD were age,BMI,higher disease activity,bowel resection(s),endoscopic activity and azathioprine use in CD;and BMI and endoscopic activity in ulcerative colitis.CONCLUSION NAFLD was highly prevalent in this cohort of German inflammatory bowel disease patients.Its risk increased mainly with rising age and BMI.This analysis provides a rationale for non-invasive liver screening in inflammatory bowel disease patients.

Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing cholangitis

AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS: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 nanoelectrospray ionization tandem mass spectrometry.RESULTS: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 mol/L)and lowest in patients with CCC(1969±981 mol/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.CONCLUSION: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.

Performance of tacrolimus in hospitalized patients with steroid-refractory acute severe ulcerative colitis

BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening 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.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS 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.RESULTSIn 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. In36.4% 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.CONCLUSION 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 steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study

BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

Real-life outcome of anti-tumor necrosis factor α in the ambulatory treatment of ulcerative colitis

AIM:To evaluate the outcome of anti-tumor necrosis factor alpha(anti-TNFα) therapy in outpatients with ulcerative colitis at a tertiary referral center.METHODS:All patients with a confirmed diagnosis of ulcerative colitis undergoing therapy with infliximab and/or adalimumab at the outpatient clinic for inflammatory bowel diseases at the University Hospital Heidelberg between January 2011 and February 2014 were retrospectively enrolled.Patients with a followup period of less than 6 mo from start of anti-TNFα therapy were excluded.Medical records of all eligible individuals were carefully reviewed.Steroid-free clinical remission of a duration of at least 3 mo,colectomy rate,duration of anti-TNFα therapy,need for anti-TNFα dose escalation,and the occurrence of adverse events were evaluated as the main outcome parameters.RESULTS:Seventy-two patients were included(35 treated with infliximab,17 with adalimumab,20 with both consecutively).Median follow-up was 27 mo(range:6-87 mo).Steroid-free clinical remission was achieved by 22.2% of the patients(median duration:21 mo until end of follow-up; range:3-66 mo).Patients attaining steroid-free clinical remission displayed lower hemoglobin and albumin blood levels at the start of treatment than those who did not achieve remission.The overall colectomy rate was 20.8%.Nearly 50% of the patients underwent anti-TNFα dose escalation during the follow-up period.For both the infliximab and the adalimumab treated patients,non-response to anti-TNFα therapy was the major reason for treatment discontinuation.18.2% of the infliximab-treated patients and 13.5% of the adalimumab-treated patients had to discontinue their therapy due to adverse events.CONCLUSION:Real-life remission rates of ulcerative colitis under anti-TNFα are overall low,but some patients have a clear long-term benefit.

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

BACKGROUND Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease(CD)in 2016,and there is an urgent need for data on its everyday use.AIM To obtain data on the daily use of ustekinumab.METHODS This is a retrospective monocentric study.Patients with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient files.The primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24±6 wk of ustekinumab therapy.Secondary study endpoints were:achievement of mucosal healing,sonographic and magnetic resonance imaging response,biochemical response,the need for intestinal surgery within 24±6 wk after treatment initiation,the occurrence of adverse events,treatment discontinuation due to nonresponse or adverse events,improvement of extraintestinal manifestations,clinical response at 48±6 wk of therapy,and association of response with nucleotid oligodimerisation domain 2 mutations.RESULTS Fifty-seven patients with CD(5.3%anti-tumour necrosis factorαnaive,63.2%having undergone at least one intestinal surgery)were included in the study.Twenty patients(35.1%)achieved steroid-free clinical remission,6(10.5%)steroid-free clinical response and 31(54.4%)were non-responders.Treatment discontinuation due to adverse events occurred in two patients(3.5%).Male sex,the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy.CONCLUSION In a“real-world”treatment-refractory cohort of patients with CD,ustekinumab appeared efficacious and safe.