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Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression. LiverScreen Consortium and the European Commission under the H20/20 program (847989); AGAUR (2017SGR-01281); Centro de Investigacion Biomedica en Enfermedades Hepaticas y Digestivas; Fundación de Investigación Sanitaria, cofunded by Instituto Carlos III–Subdirección General de Evaluación and the European Regional Development Fund (PI18/01330, PI18/00662, and PI18/00862); and Gilead’s Investigator–sponsored research program (IN-ES-989-5309)

Background COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. Patients and Methods Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. Results The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Discussion Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice., Graphical Abstract

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.Zusammenfassung Die Schwangerschaftscholestase (Intrahepatic Cholestasis of Pregnancy, ICP) ist die haufigste schwangerschaftsspezifische Lebererkrankung. Das Leitsymptom Juckreiz und eine begleitende Konzentrationserhohung von Gallensauren im Serum und/oder der Alanin-Aminotransferase (ALT) sind richtungsweisend fur die Diagnosestellung. Insgesamt ist die mutterliche Prognose gut. Das fetale Outcome ist abhangig von der Gallensaurenkonzentration. Die ICP ist sowohl mit einer Fruhgeburt als auch mit dem intrauterinem Fruchttod (IUFT) assoziiert. Ursachlich ist eine akute fetale Asphyxie und nicht eine chronische uteroplazentare Dysfunktion. Daher ist ein pradiktives Monitoring, z.B. durch CTG oder Ultraschall nicht moglich. Eine medikamentose Therapie mit Ursodeoxycholsaure (UDCA) bessert den Juckreiz - beeinflusst jedoch das fetale Outcome nicht nachweislich. Eine Entbindungsindikation ergibt sich in Abhangigkeit der Gallensaurenkonzentration und des Gestationsalters. In Folgeschwangerschaften besteht ein hohes Wiederholungsrisiko.

Introduction: Pathogenic mutations in genes encoding the hepatocanalicular transporters ATP8B1, ABCB11 and ABCB4 are causative for progressive cholestatic liver disease in children. In adults, less severe variants such as the common ABCB4 c.711A>T polymorphism have been associated with intrahepatic cholestasis in pregnancy and elevated liver enzymes. Hence, our aim was to study the role of common polymorphisms in adult patients with chronic unexplained cholestasis. Methods: Screening of outpatients of two university hospitals identified a cohort of 94 patients with chronic cholestasis of unknown origin after thorough exclusion of other causes. Genotyping was performed using TaqMan assays, and frequencies for the ABCB4 rs2109505 (c.711A>T), rs1202283 (c.504T>C), ABCB11 rs2287622 (p.A444V) and rs497692 (c.3084A>G) variants of the study cohort were compared to a cohort of 254 healthy controls. Results: The dominating symptoms of the patients were pruritus and jaundice, though the majority of them did not report symptoms at inclusion. Advanced fibrosis or cirrhosis was present in 11 patients (11.7%) only. Genotyping revealed the presence of the ABCB4 c.711A>T risk variant in 79 patients (84%), a frequency that is significantly (p = 0.037) higher than that in controls (71%). The ABCB11 p.A444V variant was also more frequent in cholestatic patients (p = 0.042). Conclusion: The common ABCB4 c.711A>T and ABCB11 p.A444V polymorphisms are more prevalent in adult patients with idiopathic cholestasis than in healthy controls and may therefore represent risk factors for the development of chronic cholestatic liver disease.

ZusammenfassungDie Qualität der ärztlichen Tätigkeit ist von zahlreichen Faktoren abhängig. Insbesondere die Prozessqualität ist durch ärztliches Handeln direkt beeinflussbar. Eine große Herausforderung ist es dabei den steten wissenschaftlichen Fortschritt in der Praxis zu folgen. Die wissenschaftlichen Standards in der Gastroenterologie werden in DGVS Leitlinien definiert und regelmäßig überarbeitet. Die Umsetzung der vielfältigen evidenzbasierten Empfehlungen in die Praxis bleibt aber anspruchsvoll. Auf Basis der DGVS Leitlinien hat die Kommission Qualität daher eine Auswahl von Qualitätsindikatoren mit besonderer Relevanz anhand standardisierter Kriterien erarbeitet, deren breite Umsetzung zu einer verbesserten Patientenversorgung in der Gastroenterologie beitragen würde.

BACKGROUND & AIMS: Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease. METHODS: We analyzed data from the European Alpha-1 Liver Cohort, from 419 adults with the Pi∗MZ genotype, 309 adults with the Pi∗ZZ genotype, and 284 individuals without the variant (noncarriers). All underwent a comprehensive evaluation; liver stiffness measurements (LSMs) were made by transient elastography. Liver biopsies were analyzed to define histologic and biochemical features associated with the Pi∗Z variant. Levels of serum transaminases were retrieved from 444,642 participants, available in the United Kingdom biobank. RESULTS: In the UK biobank database, levels of serum transaminases were increased in subjects with the Pi∗MZ genotype compared with noncarriers. In the Alpha-1 Liver Cohort, adults with Pi∗MZ had lower levels of gamma-glutamyl transferase in serum and lower LSMs than adults with the Pi∗ZZ variant, but these were higher than in noncarriers. Ten percent of subjects with the Pi∗MZ genotype vs 4% of noncarriers had LSMs of 7.1 kPa or more (adjusted odds ratio, 4.8; 95% confidence interval, 2.0-11.8). Obesity and diabetes were the most important factors associated with LSMs ≥7.1 kPa in subjects with the Pi∗MZ genotype. AAT inclusions were detected in liver biopsies of 63% of subjects with the Pi∗MZ genotype, vs 97% of subjects with the Pi∗ZZ genotype, and increased with liver fibrosis stages. Subjects with the Pi∗MZ genotype did not have increased hepatic levels of AAT, whereas levels of insoluble AAT varied among individuals. CONCLUSIONS: Adults with the Pi∗MZ genotype have lower levels of serum transaminases, fewer AAT inclusions in liver, and lower liver stiffness than adults with the Pi∗ZZ genotype, but higher than adults without the Pi∗Z variant. These findings should help determine risk of subjects with the Pi∗MZ genotype and aid in counseling. ispartof: GASTROENTEROLOGY vol:159 issue:2 pages:534-+ ispartof: location:United States status: published

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown.MethodsIn this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed.ResultsComplete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m2 : 1.23, 95% CI 1.10-1.37, P&nbsp

The pathogenesis of autoimmune complications triggered by SARS‐CoV2 has not been completely elucidated. Here, we performed an analysis of the cellular immune status, cell ratios, and monocyte populations of patients with COVID‐19 treated in the intensive care unit (ICU) (cohort 1, N = 23) and normal care unit (NCU) (cohort 2, n = 10) compared with control groups: patients treated in ICU for noninfectious reasons (cohort 3, n = 30) and patients treated in NCU for infections other than COVID‐19 (cohort 4, n = 21). Patients in cohort 1 presented significant differences in comparison with the other cohorts, including reduced frequencies of lymphocytes, reduced CD8+T‐cell count, reduced percentage of activated and intermediate monocytes and an increased B/T8 cell ratio. Over time, patients in cohort 1 who died presented with lower counts of B, T, CD4+T, CD8+T‐lymphocytes, NK cells, and activated monocytes. The B/T8 ratio was significantly lower in the group of survivors. In cohort 1, significantly higher levels of IgG1 and IgG3 were found, whereas cohort 3 presented higher levels of IgG3 compared to controls. Among many immune changes, an elevated B/T8‐cell ratio and a reduced rate of activated monocytes were mainly observed in patients with severe COVID‐19. Both parameters were associated with death in cohort 1., Patients with severe COVID‐19 present a particular set of immune changes in comparison to patients with mild disease and controls. These include consumption of certain monocyte and lymphocyte populations and an elevated B/T8 Ratio. COVID‐19 patients in general share a proinflammatory immunoglobulin profile with elevated proportions of IgG1 and/or IgG3.

OBJECTIVE To identify potentially targetable psychosocial factors associated with nonadherence to prescribed antihypertensive medications in patients presenting with hypertensive urgencies at an emergency department. METHODS This prospective study included patients treated with antihypertensive drugs who presented with hypertensive urgencies (SBP ≥180 mmHg and/or DBP ≥110 mmHg) at the emergency department of a tertiary referral clinic between April 2018 and April 2019. Health literacy was assessed using the Newest Vital Sign test. The Hospital Anxiety and Depression Scale (HADS) was used to quantify symptoms of anxiety and depression. Patients were classified nonadherent if less than 80% of the prescribed antihypertensive drugs were detectable in urine or plasma using liquid chromatography-high-resolution mass spectrometry. RESULTS A total of 104 patients (62% women) presenting with hypertensive urgencies with a median SBP of 200 mmHg (IQR 190-212) and DBP of 97.5 mmHg (IQR 87-104) were included. Twenty-five patients (24%) were nonadherent to their antihypertensive medication. Nonadherent patients were more often men (66 versus 23%, P = 0.039), prescribed higher numbers of antihypertensive drugs (median 3, IQR 3-4 versus 2, IQR 1-3; P

Background: Approximately one fifth of adults are diagnosed with gallstones worldwide. Of these, around 25% develop gallstone disease (indicated by the presence of symptoms) and undergo cholecystectomy. Summary: The risk of gallstones is influenced by a combination of genetic and lifestyle factors, such as excess body weight. In fact, body mass has been demonstrated to be a major risk factor for symptomatic gallstones. Rapid weight loss can also initiate a prolithogenic state and further increase the likelihood of either gallstone formation or existing gallstones becoming symptomatic; however, sensible weight loss strategies can mitigate this risk. This review discusses the role of excess body weight and the risk of gallstone disease, as well as the options available for the prevention of symptomatic gallstones. Key Messages: Healthy weight loss diets combined with regular physical activity can promote successful weight loss and weight maintenance and reduce the risk of gallstones. Should rapid weight loss be required for health reasons or be expected, e.g., after bariatric surgery, prophylactic ursodeoxycholic acid during the period of weight reduction has been demonstrated to reduce the incidence of gallstones formation or symptomatic gallstone occurrence. The recent German guidelines on gallstones recommend simultaneous cholecystectomy during bariatric surgery but only for those with preexisting symptomatic stones.

Introduction: The endoplasmic reticulum transmembrane proteins Sec61, Sec62, and Sec63 are responsible for the intracellular trafficking of precursor proteins and affect intracellular signaling. SEC62 overexpression has been linked to various human cancers. Our aim was to investigate SEC62 and SEC63 expression in hepatocellular carcinoma (HCC) and surrounding liver tissue. Patients and Methods: Primary liver tissue was collected from 11 consecutive patients (70 ± 9 years; 10 men) who underwent HCC resection. In the HCC and the tumor-surrounding liver tissue we investigated SEC62 und SEC63 mRNA expression using quantitative real-time PCR. For Sec62, immunohistochemistry was performed. Results: SEC62and SEC63 total mRNA contents were significantly (p = 0.001) higher in HCCs (CT 22.5 ± 0.4 and 22.6 ± 0.3) when compared to the surrounding tissue (CT 24.6 ± 0.6 and 25.1 ± 0.9). Using the comparative CTmethod, SEC62 and SEC63 expression in HCC was increased 5- and 8.1-fold, respectively, in comparison to surrounding tissue. For Sec62 immunohistochemistry, the mean immunoreactive scores (IRS) were 7.9 ± 2.9 for HCC and 4.8 ± 1.2 for non-tumorous liver (p = 0.027). The mean IRS in HCC were 5.7 ± 3.5 and 8.9 ± 2.3 for patients without (n = 3) and with tumor recurrence (n = 8), respectively. Conclusions: Overexpression of SEC62 and SEC63 is a common feature of HCC. The role of Sec62 as a prognostic marker for tumor recurrence after surgery and its potential role in treatment stratification must be addressed in future studies.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive cholestatic disease characterized by intermittent cholestatic episodes of variable severity and duration. BRIC type 1 has been linked to gene mutations encoded in the hepatocanalicular transporter ATP8B1.1 It has been suggested that ATP8B1 affects the regulation of the farnesoid X receptor, and thus ATP8B1 deficiency could lead to an imbalance between intestinal absorption of bile acids and hepatic secretion, causing bile acid accumulation.2 The latter aggravates hepatocellular dysfunction leading to a vicious cycle.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFN alpha-2a) is the only effective treatment but its long-term clinical impact is unclear. the aim of this study was to investigate the long-term outcome after 48 weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48 weeks of treatment with either PEG-IFN alpha-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFN alpha-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFN alpha-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n = 19), Group II (n = 20), Group III (n = 21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n = 8) in PEG-IFN alpha-2a arms and 58% (n = 11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. the annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFN alpha-2a treatment leads to improved clinical long-term outcome., German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig; German Liver Foundation; EASL registry grant, This study was funded by the German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig with a grand to the HepNet Study-House, the German Liver Foundation and an EASL registry grant.

ZusammenfassungSeit der Einführung des G-DRG-Systems zur Vergütung der stationären Krankenversorgung im Jahr 2003 werden durch das Institut für das Entgeltsystem im Krankenhaus (InEK) jährlich die Erstattungsbeträge für alle Fallgruppen (DRG) auf der Basis des Mittelwerts der Kostendaten (§-21-KHEntgG-Datensatz) von ca. 200 kalkulierenden Krankenhäusern berechnet. Nach dieser Systematik müsste die eine Hälfte der stationären Leistungserbringer Überschüsse in der Krankenversorgung erwirtschaften, die andere Hälfte Verluste ausweisen. Trotz langjähriger Optimierung ihrer Kosten weisen jährlich zwei Drittel der Universitätsklinika operative Defizite aus, unter den nicht universitären Häusern sind es dagegen 29 %. Die Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) hat als wissenschaftliche Fachgesellschaft seit 2012 von 74 für das InEK kalkulierenden und mit der DGVS kooperierenden Krankenhäusern die anonymisierten Kostendaten von mehr als 7 Mio. Abrechnungsfällen ausgewertet, um damit eine sachgerechtere Darstellung gastroenterologischer DRG durch datenbasierte Anträge an das InEK zu ermöglichen. Diese Daten wurden jetzt verwendet, um an drei Beispielen repräsentativer DRG und Operationen- und Prozedurenschlüssel (OPS) (hepatische Enzephalopathie bei Leberzirrhose, endoskopische Leistungsgruppen und Behandlungskosten von zwischen Krankenhäusern für eine Intervention verlegten Patienten) die Möglichkeiten und Grenzen der sachgerechten Darstellung universitätsmedizinischer Leistungserbringung im G-DRG-System zu untersuchen. Die Analyse ergibt, dass eine ökonomisch angemessene Kostenabbildung der komplexeren und schwerer erkrankten Patienten an den Universitätsklinika im G-DRG-System nicht durch Korrekturen oder eine Weiterdifferenzierung innerhalb des bestehenden Systems möglich ist. Selbst in Fallgruppen, in denen eine Korrektur möglich wäre, ist sie im bestehenden System teilweise untersagt. Einem weiteren Anstieg des operativen Defizits der Universitätsklinika in der Krankenversorgung (zuletzt kumulativ 300 Mio. Euro) kann nur durch entweder einen fallbezogenen Systemzuschlag oder die Trennung eines universitätsmedizinischen U-DRG-Systems vom allgemeinen G-DRG-System entgegengewirkt werden.

Gallstones develop in the gallbladder or the bile ducts. According to their chemical composition, gallstones can be divided into cholesterol stones, which are common, and the rare bile pigment stones. Altogether, up to 20 % of all adults develop gallstones and more than 20 % of them symptoms or complications. Female sex, age, pregnancy, physical inactivity, obesity, overnutrition and genetic factors such as ABCB4 deficiency of the hepatic lecithin transporter are kown risk factors for gallstone formation. In about one half of all patients biliary symptoms precede the three common and potentially life-threatening complications (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge about the genetics and pathophysiology of gallstones has improved, current treatment algorithms are predominantly invasive (ERC and surgery). Thus, better strategies are needed to prevent the formation of gallstones in general.

Liver steatosis is one of the side effects of chemotherapy. The PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 p.G17E variants represent genetic determinants for progressive liver diseases. Here, we investigate their association with chemotherapy-associated steatosis.Prospectively, we recruited 87 patients undergoing systemic chemotherapy for gastrointestinal cancers. Hepatic fat (controlled attenuation parameter, CAP) and liver stiffness (LSM) were measured non-invasively before the initiation of chemotherapy (T0) and after at least two (T1) and four cycles (T2). Genetic variants were genotyped using allelic discrimination assays.In the final dataset (n = 60) patients demonstrated the following CAP values: T0 - 215.0 ± 55.7 dB/m, T1 - 223.3 ± 53.6 dB/m, T2 - 223.4 ± 56.7 dB/m, consistent with mild steatosis. Initial CAP correlated with BMI (P 0.01) and serum triglyceride concentrations (P = 0.03). Whereas at T0 none of the variants was associated with CAP or LSM, carriers of the prosteatotic PNPLA3 p.148M allele showed significantly (P = 0.008) higher steatosis at T1 as compared to patients carrying the homozygous wild-type genotype [II].Our preliminary results show that patients carrying the PNPLA3 p.I148 M risk allele might be prone to hepatic fat accumulation during chemotherapy. Further studies are be needed to validate the clinical value of these findings.

ObjectiveAlpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the ‘Pi*Z’ variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous ‘Pi*Z’ carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common ‘Pi*S’ variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD.DesignBaseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption.ResultsAmong UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8–53.7)) and primary liver cancer (aOR=44.5 (10.8–183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2–2.2)) and cholelithiasis (aOR=1.3 (1.2–1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1–8.2)) and primary liver cancer (aOR=6.6 (1.6–26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.ConclusionOur study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.

ObjectiveTo investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA).DesignA multicentre, prospective, international cohort study.Setting43 gastroenterology and endoscopy centres located in Europe and South America.Participants2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications.InterventionsA 3-year follow-up was performed.Main outcome measuresTo predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score).ResultsThe 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981).ConclusionsDICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score.Trial registration numberNCT02758860.

ObjectiveHealthcare workers (HCW) are at high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate the prevalence of infection among HCW in medical disciplines with AGP.DesignA nationwide questionnaire-based study in in- and outpatient settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCW and potential risk factors were investigated.Results2,070 healthcare facilities with 25,113 employees were included in the study. Despite a higher rate of pre-interventional testing, clinics treated three times more confirmed SARS-CoV-2 cases than private practices (28.8% vs. 88.4%, pConclusionHCW in GIE seem to be at higher risk of infection than those in other AGP, especially in the clinical setting. Regions having comparably higher incidences as well as the number of procedures performed per day were also significantly associated with increased risk of infection.Significance of this studyWhat is already known on this subject?Health care workers, especially those exposed to aerosol generating procedures, are assumed to have an increased risk of SARS-CoV-2 infection. However, data confirming this are lacking, especially for the outpatient care setting.What are the new findings?Health care workers in gastrointestinal endoscopy have a higher risk of SARS-CoV-2-infection than in other AGPs. This risk is particularly higher-in clinical settings compared to private practices-in regions having comparably higher incidences-the more procedures are performed per dayHow might it impact on clinical practice in the foreseeable future?Our study suggests making additional efforts to protect HCW in the gastrointestinal work field.

Zusammenfassung Hintergrund In der Bewältigung der COVID-19-Pandemie stehen Praxen und Kliniken vor großen Herausforderungen. Zu den Auswirkungen der Pandemie auf gastroenterologische Einrichtungen, insbesondere über einen zeitlichen Verlauf, gibt es bislang kaum Daten. Besonders für den ambulanten Versorgungssektor fehlt eine Datenbasis. Das Universitätsklinikum Augsburg wurde im Rahmen des Verbundprojektes B-FAST des Nationalen Forschungsnetzwerks der Universitätsmedizin beauftragt hierzu Daten zu generieren. Methode Es wurden bundesweit mittels Onlinefragebogen gastroenterologische Einrichtungen befragt. Die Rekrutierung erfolgte über die Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und den Berufsverband niedergelassener Gastroenterologen (bng). Das vorliegende Manuskript gibt einen Überblick über Daten zur Verwendung von Schutzausrüstung, präinterventioneller Testung von Patienten, Mitarbeiterscreenings sowie wirtschaftlichen Auswirkungen über den Pandemieverlauf. Ergebnisse 429 Einrichtungen beantworteten den Fragebogen. Praxen testeten ihre Patienten präinterventionell signifikant seltener als Kliniken (7,8 % vs. 82,6 %). In Kliniken wurden stationäre Patienten (93,1 %) signifikant häufiger getestet als ambulante Patienten (72,2 %). Die Verwendung von persönlicher Schutzausrüstung (PSA) nahm im Verlauf der Pandemie signifikant zu. Es konnte gezeigt werden, dass über 70 % der Einrichtungen ihre Mitarbeiter nicht-anlassbezogen auf SARS-CoV-2 screenten. Kliniken sagten im Quartal 4/2020 signifikant häufiger elektive Prozeduren ab als Praxen. Die durchgeführten Prozeduren und die Umsatzentwicklung nahmen 2020 im Vergleich zum Vorjahr ab. Jedoch waren weniger Einrichtungen von einem Umsatzverlust betroffen als in vorangegangenen Studien erwartet wurde. Schlussfolgerung Unserer Daten veranschaulichen die unterschiedliche Umsetzung präinterventioneller SARS-CoV-2 Testung in der ambulanten und stationären Patientenversorgung. Die Verwendung adäquater PSA und Mitarbeiterscreeningmaßnahmen konnten im Verlauf der Pandemie gesteigert werden.

Copyright © 2021 Marques, Afonso, Bierig, Duarte-Ramos, Santos-Laso, Jimenez-Agüero, Eizaguirre, Bujanda, Pareja, Luís, Costa, Machado, Alonso, Arretxe, Alustiza, Krawczyk, Lammert, Tiniakos, Flehmig, Cortez-Pinto, Banales, Castro, Normann and Rodrigues. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms., Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p < 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis., CR was funded by FEDER through the COMPETE program and by national funds through Fundação para a Ciência e a Tecnologia (PTDC/MED-FAR/29097/2017—LISBOA-01-0145-FEDER-029097) and by European Horizon 2020 (H2020-MSCA-RISE-2016-734719). This work was also supported by Fundação para a Ciência e Tecnologia (PD/BD/135467/2017) and Portuguese Association for the Study of Liver/MSD 2017. JB was funded by Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008), co-financed by Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III (CIBERehd, Spain), La Caixa Scientific Foundation (HR17-00601), Fundación Científica de la Asociación Española Contra el Cáncer, and European Horizon 2020 (ESCALON project: H2020-SC1-BHC-2018-2020).

Background & Aims Treatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH. Methods Clinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period. Results Twenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19–79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3–28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p ≪0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1–10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded. Conclusion In patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated with sustained improvements in serum liver tests, an absence of clinical disease flares, and a reduction in prednisolone dose. Controlled trials are warranted to further evaluate B cell-targeting therapies in patients with AIH. Lay summary Autoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to first- or second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome., Graphical abstract Unlabelled Image, Highlights • Study of rituximab therapy in 22 patients with autoimmune hepatitis over a follow-up period of 24 months. • No serious adverse events were noted during follow-up in patients treated with rituximab. • Rituximab therapy improved liver enzymes significantly during the 2 years of follow-up. • Prednisolone dose reductions were seen in 62% of patients at 12-month follow-up. • A total of 71% of patients were free of AIH flares during the 24 months of follow-up.

Non-alcoholic fatty liver disease (NAFLD) parallels comorbidities such as metabolic syndrome, dyslipidaemia or diabetes. Although NAFLD is very prevalent in overweight-obese individuals (i.e. body mass index ≥25 kg/m2), recent studies point to the presence of NAFLD in non-obese individuals, for both the Asian (25 kg/m2) and Caucasian (30 kg/m2) populations. This paper discusses the pathogenic pathways and current treatment options of NAFLD in non-obese populations. In this respect, non-obese subjects also need to undergo the medical screening for NAFLD. Across the scientific community, we aim to promote the advancement of knowledge in this emerging field.

Zusammenfassung Einleitung Die gezielte Förderung des ärztlichen Nachwuchses ist in der Gastroenterologie unerlässlich. Ziel dieser Studie war es, Faktoren zu identifizieren, die Mitglieder der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) dazu bewogen haben, die Gastroenterologie als Fachgebiet auszuwählen. Methoden Die Umfrage wurde online an alle DGVS-Mitglieder versendet. Es wurden folgende Faktoren beurteilt: frühester Entschlusszeitpunkt für das Fachgebiet Gastroenterologie, bedeutsame Mentoren und Vorbilder, beeinflussende Studieninhalte, die Rolle der Doktorarbeit und weitere Aspekte der Gastroenterologie. Ausgewertet wurden die Ergebnisse aller Teilnehmer mit Subgruppenanalysen in Bezug auf Berufserfahrung (≤ 8, 9–29, ≥ 30 Jahre) und Tätigkeitsort (Universitätsklinikum, kommunales Krankenhaus, gastroenterologische Schwerpunktpraxis). Ergebnisse Es wurden 1358 Fragebogen ausgefüllt (Rücklaufquote 24,2 %). Befragte mit ≤ 8 Jahren Berufserfahrung haben sich zu 62,5 % bereits im Rahmen des Studiums entschieden, sich als Gastroenterologe/-in zu spezialisieren; bei Befragten mit ≥ 9 Berufserfahrungsjahren waren dies 37,1 % (p Schlussfolgerungen Der Entschluss, die Gastroenterologie als Spezialgebiet zu wählen, fällt größtenteils bereits im Studium. Oberärzte/-innen spielen als Mentoren eine entscheidende Rolle. Besonders praktische Studieninhalte wie Sonografie, aber auch Endoskopie sind bedeutsame Einflussfaktoren für die Wahl des Fachs.

ZusammenfassungNeuroendokrine Neoplasien (NEN) umfassen eine seltene Tumorentität mit heterogener Biologie, Prognose und therapeutischen Optionen. In Zusammenhang mit der kürzlichen Publikation der ersten deutschen Leitlinie zur Diagnostik und Therapie von NEN erfolgte die Analyse der Kohorte des Deutschen NET-Registers der Deutschen Gesellschaft für Endokrinologie (DGE). Hierzu wurden 2686 Fälle extrahiert und ihre Patientencharakteristika wie Alter, Geschlecht, Primärtumorlokalisation, Grading und Staging dargestellt sowie das Gesamtüberleben berechnet. Zusätzlich wurden die systemischen Behandlungsstrategien in den beiden größten Untergruppen, NEN des Dünndarms und Pankreas, im Stadium der Metastasierung analysiert.Die Verteilung der Primärtumoren, die histopathologische Charakterisierung, das Tumorstadium sowie das Gesamtüberleben waren vergleichbar mit den Ergebnissen internationaler Registerstudien. Somatostatinanaloga (SSA) und die Peptid-Rezeptor-Radionuklid-Therapie (PRRT) waren die häufigsten systemischen Therapieverfahren bei Dünndarm-NEN. Hingegen wurde eine Chemotherapie – in Übereinstimmung mit der neuen Leitlinie – vor allem bei pankreatischen NEN eingesetzt und kam in der Erstlinie in ähnlicher Frequenz wie die SSA-Therapie bzw. in der Zweitlinie ähnlich häufig wie eine PRRT zum Einsatz. Prognostisch relevante Parameter waren die WHO-Klassifikation 2010 und das TNM-Staging.Die aktuelle Analyse des deutschen NET-Registers charakterisiert damit eine multizentrische, interdisziplinäre, deutschlandweite Kohorte von NEN-Patienten und beschreibt die angewendeten systemischen Therapieverfahren, das Gesamtüberleben und die prognostische Bedeutung der WHO-Klassifikation 2010 sowie des TNM-Stadiums.

Was ist neu? Digitalisierung in der personalisierten Medizin Fortschritte in der genomischen Diagnostik und digitale innovative Technologien lassen die personalisierte Therapie gastrointestinaler entzündlicher und onkologischer Erkrankungen bald möglich erscheinen. Digitalisierung in der interventionellen Diagnostik und Therapie In der interventionellen Gastroenterologie lassen sich neue IT-gestützte Diagnostik- und Therapieverfahren und Formen der Mensch-Technik-Kollaboration gut testen und im Versorgungalltag validieren. Digitale Kompetenzen und Kommunikation Um die Arzt-Patienten-Kommunikation auf Augenhöhe zu erhalten, müssen auf beiden Seiten Kompetenzen im Umgang mit digitalen Anwendungen aufgebaut werden. Qualitativ hochwertige digitale Gesundheitsprodukte im unübersichtlichen Markt zu identifizieren bleibt eine Herausforderung. Wissensmanagement und ärztliche Weiterbildung Die Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselerkrankungen entwickelt digitale Angebote für verschiedene Interessengruppen und engagiert sich bei der Wissensvermittung über soziale Netzwerke. Die ärztliche Weiterbildung im Zeitalter der Digitalisierung ist ebenfalls ein wichtiges Thema. Implementierungsprobleme und Handlungsoptionen Um die Qualität technologischer Innovationen zu steigern und einen erfolgreichen Transfer in die Versorgung zu ermöglichen ist eine engere Kooperation zwischen Patienten, praktisch tätigen Ärzten und technischen Experten unabdingbar. Entsprechende Strukturen hierfür fehlen weitgehend.

Zusammenfassung Einleitung Mit dem Reizdarm-Fragebogen (RDF) wurde erstmals ein deutschsprachiges Instrument zur Erfassung der subjektiv wahrgenommenen Symptombelastung bei einem Reizdarm-Syndrom (RDS) vorgestellt. Bis dato lagen ausschließlich Instrumente zur ärztlichen Einschätzung der Symptomschwere in deutscher Sprache vor. Das Ziel der vorliegenden Arbeit war es, Unterschiede zwischen RDS-Patienten und verschiedenen klinischen und nicht-klinischen Kontrollgruppen hinsichtlich der Skalen des Fragebogens zu untersuchen sowie einen Cut-Off-Wert für das Vorliegen eines RDS zu ermitteln. Auf Basis eines solchen Cut-Off-Werts sollte die Qualität des RDF als Screening-Instrument beurteilt werden. Material und Methoden An der Studie nahmen 372 Personen teil (62,6% männlich, mittleres Alter=41±17 Jahre). 17,5% der Teilnehmer hatten eine RDS-Diagnose, 19,9% wurden wegen einer chronisch-entzündlichen Darmerkrankung behandelt, 12,1% waren Patienten in einer psychosomatischen Reha-Klinik und 50,5% gehörten zu einer gesunden Kontrollgruppe. Alle Teilnehmer füllten den 13 Items umfassenden RDF aus. Ergebnisse Hinsichtlich des RDF-Gesamtwerts zeigten sich signifikante Unterschiede zu allen anderen klinischen- und nicht-klinischen Kontrollgruppen [t(98,82)=13,61, p Diskussion und Schlussfolgerung Der RDF kann als effizientes Instrument zur Erfassung der subjektiv wahrgenommenen Symptombelastung bei RDS gelten. Mit seinen sehr guten psychometrischen Qualitäten kann er sowohl im klinischen als auch im wissenschaftlichen Kontext als Screening-Instrument eingesetzt werden.

Was ist neu? Prävention von Gallensteinen Lifestyleänderungen im Sinne von regelmäßiger körperlicher Aktivität und bedarfsgerechter Ernährung können der Entwicklung von Cholesteringallenblasensteinen vorbeugen. Ursodeoxycholsäure sollte bei ABCB4-Defizienz präventiv eingesetzt werden. Diagnostik Der Nachweis einer akuten Cholezystitis soll primär sonografisch in Kombination mit den klinischen Befunden erfolgen. Die Endosonografie sollte bei unklaren Fällen wegen ihrer hohen Sensitivität und Spezifität für Gallengangsteine eingesetzt werden. Therapie Die medikamentöse Therapie der biliären Kolik sollte mit nichtsteroidalen Antiphlogistika erfolgen. Die akute Cholezystitis stellt eine Indikation zur frühzeitigen (innerhalb von 24 Stunden nach stationärer Aufnahme) laparoskopischen Cholezystektomie dar. Nach ERC bei Choledocholithiasis sollte bei Cholezystolithiasis eine frühe (innerhalb von 72 Stunden) Cholezystektomie durchgeführt werden, ebenso nach milder biliärer Pankreatitis (während desselben stationären Aufenthalts).

ObjectiveDiverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease.DesignDiscovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry.ResultsWe discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (pCTAGE1 with a p value of 2.3×10−10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33).ConclusionIn silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.

Background/Aims: The PNPLA3 loss-of-function variant p.I148M is a strong genetic determinant of nonalcoholic fatty liver disease. The PNPLA3 protein functions as an intracellular lipase in the liver, with a greater activity on unsaturated fatty acids. This study aimed to determine whether short-term supplementation with omega-3 fatty acids impacts hepatic steatosis differently in PNPLA3 p.148I wild-type individuals as compared to homozygous carriers of the PNPLA3 p.148M variant. Methods: Twenty subjects with hepatic steatosis (50% women, age 18–77 years) were included. Ten subjects homozygous for the PNPLA3 148M variant were matched to 10 wild-type individuals. The subjects received 4 g omega-3 fatty acids (1,840 mg eicosapentaenoic acid and 1,520 mg docosahexaenoic acid) a day for 4 weeks. Transient elastography with a controlled attenuation parameter (CAP) was used to quantify liver fat before and after the intervention. Body composition, fibrosis, liver function tests, serum free fatty acids (FFA) and glucose markers were compared. Results: Patients homozygous for the PNPLA3 p.148M variant (risk group) demonstrated no significant changes in CAP compared to baseline (284 ± 55 vs. 287 ± 65 dB/m) as did the control group (256 ± 56 vs. 262 ± 55 dB/m). While serum liver enzyme activities remained unchanged in both groups, the risk group displayed significantly (p = 0.02) lower baseline FFA concentrations (334.5 [range 281.0–431.0] vs. 564.5 [range 509.0–682.0] μmol/L), which markedly increased by 9.1% after the intervention. In contrast, FFA concentrations decreased significantly (p = 0.01) by 28.3% in the wild-type group. Conclusions: Short-term omega-3 fatty acid supplementation did not significantly alter hepatic steatosis. The nutrigenomic and metabolic effects of omega-3 fatty acids should be investigated further in carriers of the PNPLA3 148M risk variant.

Background & aims Bacterial infections (BI) affect the natural course of cirrhosis and were suggested to be a landmark event marking the transition to the decompensated stage. Our specific aim was to evaluate the impact of BI on the natural history of compensated cirrhosis. Methods We analyzed 858 patients with cirrhosis, evaluated for the INCA trial (EudraCT 2013-001626-26) in 2 academic medical centers between February 2014 and May 2019. Only patients with previously compensated disease were included. They were divided into 4 groups: compensated without BI, compensated with BI, 1st decompensation without BI, and 1st decompensation with BI. Results About 425 patients (median 61 [53-69] years) were included in the final prospective analysis. At baseline, 257 patients were compensated (12 [4.7%] with BI), whereas 168 patients presented with their 1st decompensation (42 [25.0%] with BI). In patients who remained compensated MELD scores were similar in those with and without BI. Patients with their first decompensation and BI had higher MELD scores than those without BI. Amongst patients who remained compensated, BI had no influence on transplant-free survival, whereas patients with their 1st decompensation and concurrent BI had significantly reduced transplant-free survival as compared with those without BI. The development of BI or decompensation during follow-up had a greater impact on survival than each of these complications at baseline. Conclusions In compensated patients with cirrhosis, the 1st decompensation associated to BI has worse survival than decompensation without BI. By contrast, BI without decompensation does not negatively impact survival of patients with compensated cirrhosis.

Background & Aims Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. Methods In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Results Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711–1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697–1.430; p = 0.992 and HR 1.058; 95% CI 0.727–1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. Conclusions In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. ClinicalTrials.gov number NCT02669680 Lay summary Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by increased serum bile acid levels in the third trimester of pregnancy and resolves quickly after delivery. Here, we present the case of a 29-year-old woman who developed idiopathic liver damage during puberty, and subsequently ICP and severe pruritus during two pregnancies. DNA sequencing revealed a heterozygous deletion (c.393_delG) in the fibroblast growth factor receptor 4 (FGRF4) gene causing a premature stop codon. The resulting FGFR4 haploinsufficiency is likely to impede the enterohepatic feedback repression of hepatic bile acid synthesis via FXR and FGF19. It represents a new genetic etiology of ICP.

Background and Aims: Colonic diverticulosis (CD) is among the most common conditions of the large bowel. Several factors have been associated with an increased risk of CD and its complications, including advanced age, obesity, physical inactivity, and a low-fiber diet. Available data is conflicting and a comprehensive analysis of different bowel, dietary and environmental habits linked with CD is lacking. We aimed to investigate the relationship between potential risk factors and CD prevalence using full data from a colonoscopy-based cross-sectional study in Europe. Methods: The study was conducted at three tertiary referral centers in Germany and Lithuania. It included consecutive adult patients referred for routine colonoscopy who completed a detailed questionnaire on our considered multiple risk factors for diverticulosis and diverticulitis, including dietary and environmental factors, and bowel habits. Results: The study included 1,333 patients, 696 women and 635 men. Colonic diverticulosis was diagnosed in 858 (64%) of patients. Multivariate analysis revealed that age (OR: 1.08, 95%CI: 1.06–1.10, p

Zusammenfassung Einleitung Die COVID-19-Pandemie stellt die Gesundheitssysteme weltweit vor eine große Herausforderung. Aktuelle Daten deuten auf ein erhöhtes Risiko für eine SARS-CoV-2-Infektion für das Endoskopiepersonal hin. Für gastrointestinale Endoskopieeinheiten wurden mehrere Empfehlungen für die aktuelle Situation formuliert, jedoch liegen bislang keine Daten zur momentanen Versorgungsrealität vor. Material und Methodik Vom 1. bis 7. April 2020 erfolgte eine deutschlandweite, webbasierte Umfrage unter den Mitgliedern der DGVS. Insgesamt wurden 33 Fragen gestellt, die auf Empfehlungen der ESGE (European Society of Gastrointestinal Endoscopy) basierten. Die Umfrage war an die Leiter von Endoskopieeinheiten gerichtet. Ergebnisse Von 551 teilnehmenden Endoskopieeinheiten stornierten 37 % (202) weniger als 40 % ihrer Eingriffe. Kleinere Abteilungen ( 4000). Eine vollständige räumliche Trennung von Hochrisikopatienten war nur in 17 % der Fälle möglich. Prozedurale Maßnahmen wie strukturierte Risikostratifikation (91 %) oder Verwendung persönlicher Schutzausrüstung (PSA, 85 %) wurden meist umgesetzt. Für die Zukunft wurden Engpässe bei PSA (83 %) und Personal (69 %) sowie relevante finanzielle Verluste (80 %) erwartet. Schlussfolgerungen Die Empfehlungen zu den strukturellen Maßnahmen waren nur eingeschränkt umsetzbar, und der Umfang von Stornierungen war heterogen. Eindeutige Definitionen notwendiger Endoskopien in der Pandemiesituation und eine Anpassung struktureller Gegebenheiten sowie eine finanzielle Absicherung erscheinen notwendig.

Patients with pre-existing comorbidities and immunosuppression are at greater risk for SARS-CoV-2 infection and severe manifestations of COVID-19. This also includes cancer patients, who are shown to have a poor prognosis after infection. Here, we describe the case of a 72-year old male patient with B-cell depletion after maintenance treatment with rituximab for non-Hodgkin-lymphoma who had a prolonged COVID-19 course and initial false negative test results. Our case highlights the diagnostic pitfalls in diagnosing COVID-19 in B-cell depleted patients and discuss the role of B-cell depletion in the course and treatment of COVID-19. Furthermore, we investigated peripheral blood monocytes and SARS-CoV-2 specific T cells in our patient. In conclusion, our case report can help physicians to avoid diagnostic pitfalls for COVID-19 in hemato-oncological patients under chemoimmunotherapy and tries to explain the role of B-cell depletion and SARS-CoV-2 specific T cells in this context.

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.

The outbreak of coronavirus disease 2019 (COVID-19) starting last December in China placed emphasis on liver involvement during infection. This review discusses the underlying mechanisms linking COVID-19 to liver dysfunction, according to recent available information, while waiting further studies. The manifestations of liver damage are usually mild (moderately elevated serum aspartate aminotransferase activities), and generally asymptomatic. Few patients can still develop severe liver problems, and therapeutic options can be limited. Liver dysfunction may affect about one-third of the patients, with prevalence greater in men than women, and in elderly. Mechanisms of damage are complex and include direct cholangiocyte damage and other coexisting conditions such as the use of antiviral drugs, systemic inflammatory response, respiratory distress syndrome-induced hypoxia, sepsis, and multiple organ dysfunction. During new COVID-19 infections, liver injury may be observed. If liver involvement appears during COVID-19 infection, however, attention is required. This is particularly true if patients are older or have a pre-existing history of liver diseases. During COVID-19 infection, the onset of liver damage impairs the prognosis, and hospital stay is longer.

Background Transarterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC) in cirrhosis. In particular in advanced cirrhosis, post-TACE hepatic failure liver (PTHF) failure may develop. Currently, there is no standardization for the periinterventional risk assessment. The liver maximum capacity (LiMAx) test assesses the functional liver capacity, but has not been investigated in this setting. Aims The aim of this study was to prospectively evaluate periinterventional LiMAx and CT volumetry measurements in patients with cirrhosis and HCC undergoing repetitive TACE. Methods From 06/2016 to 11/2017, eleven patients with HCC and cirrhosis undergoing TACE were included. LiMAx measurements (n = 42) were conducted before and after each TACE. Laboratory parameters were correlated with the volume–function data. Results The median LiMAx levels before (276 ± 166 µg/kg/h) were slightly reduced after TACE (251 ± 122 µg/kg/h; p = 0.08). This corresponded to a median drop of 7.1%. Notably, there was a significant correlation between LiMAx levels before TACE and bilirubin (but not albumin nor albumin–bilirubin [ALBI] score) increase after TACE (p = 0.02, k = 0.56). Furthermore, a significantly higher increase in bilirubin in patients with LiMAx ≤ 150 µg/kg/h was observed (p = 0.011). LiMAx levels at different time points in single patients were similar (p = 0.2). Conclusion In our prospective pilot study in patients with HCC and cirrhosis undergoing multiple TACE, robust and reliable LiMAx measurements were demonstrated. Lower LiMAx levels before TACE were associated with surrogate markers (bilirubin) of liver failure after TACE. Specific subgroups at high risk of PTHF should be investigated. This might facilitate the future development of strategies to prevent occurrence of PTHF.