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1. Use of complementary and alternative medicine in patients with chronic liver diseases in Germany- a multicentric observational study

Author

Fleur Sophie Gittinger, Anna Rahnfeld, Elena Lacruz, Alexander Zipprich, Frank Lammert, and Cristina Ripoll

Subjects
CAM, Chronic liver disease, Other systems of medicine, RZ201-999
Abstract

Abstract Background The use of Complementary and alternative medicine (CAM) in chronic liver disease (CLD) patients in Germany is unknown. This study investigated the frequency of CAM use and associated sociodemographic, clinical and personality factors in CLD patients in Germany. Methods This is a cross-sectional multicenter study of CLD patients attending liver outpatient clinics of university hospitals in Halle(-Saale) and Homburg between 2015 and 2017. Dedicated questionnaires recorded CAM use, sociodemographic and personality factors (evaluated with the “Big five” model, “Hospital Anxiety and Depression”-, “Multidimensional Health Locus of Control”- score). Uni- and multivariate analyses assessed factors associated to CAM use. Results Overall 378 patients were recruited, 92 (24.3%) reported to CAM use. On univariate analysis, female CAM users were older (p = 0.001) and more physically active (p = 0.002), male CAM users more often used homeopathy (p = 0.000), actively promoted their health (p = 0.010) or had UDC in their medication (p = 0.004). Logistic regression analysis adjusted for personality factors showed significant association of age, physical exercise (females) and satisfaction with alternative medicine (females, males) to CAM use. Conclusions CAM use is prevalent among CLD patients in Germany and is significantly associated to satisfaction with alternative medicine (females, males), physical exercise and older age (females). Doctors should actively inquire CLD patients about CAM use, as hepatotoxicity or interaction with medication can occur.

Published
2024
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2. Skin advanced glycation end-products as indicators of the metabolic profile in diabetes mellitus: correlations with glycemic control, liver phenotypes and metabolic biomarkers

Author

Grigorios Christidis, Frederic Küppers, Senem Ceren Karatayli, Ersin Karatayli, Susanne N. Weber, Frank Lammert, and Marcin Krawczyk

Subjects
AGE, Diabetes, FGF, GDF15, Liver fibrosis, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract Introduction The production of advanced glycation end-products (AGEs) is a key pathomechanism related to the complications of diabetes mellitus. The measurement of HbA1c as one of the AGEs is widely used in the clinic, but also other proteins undergo glycation in the course of diabetes. Here, we measure skin AGEs (SAGEs) in patients with diabetes type 1 (DM1) and type 2 (DM2) and correlate them with metabolic markers as well as non-invasively measured liver fibrosis and steatosis. Patients and methods In this cross-sectional study, a total of 64 patients with either DM1 or DM2 and 28 healthy controls were recruited. SAGEs were measured using autofluorescence (AGE Reader). Liver fibrosis and steatosis were quantified using transient elastography, which determines liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). FGF19, FGF21 and GDF-15 were measured in blood samples using ELISA. Results SAGEs were elevated in both groups of patients with diabetes as compared to healthy controls (both p

Published
2024
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3. Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis

Author

Rebekka J.S. Salzmann, Christina Krötz, Tudor Mocan, Lavinia P. Mocan, Cristiana Grapa, Sophia Rottmann, Ramona Reichelt, Cindy M. Keller, Bettina Langhans, Frederik Schünemann, Alexander Pohl, Thomas Böhler, Käthe Bersiner, Marcin Krawczyk, Piotr Milkiewicz, Zeno Sparchez, Frank Lammert, Sebastian Gehlert, Maria A. Gonzalez-Carmona, Arnulf Willms, Christian P. Strassburg, Miroslaw T. Kornek, Leona Dold, and Veronika Lukacs-Kornek

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background:. The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. Methods:. Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. Results:. Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p

Published
2024
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4. How do (false) positively screened patients experience a screening programme for liver cirrhosis or fibrosis in Germany? A qualitative study

Author

Urs A. Fichtner, Anita Arslanow, Harald Binder, Peter R. Galle, Christian Labenz, Frank Lammert, Julia Ortner, Dominikus Stelzer, Louis Velthuis, and Erik Farin‐Glattacker

Subjects
cirrhosis, fibrosis, liver screening, patient‐reported outcomes, psychosocial consequences, Medicine (General), R5-920, Public aspects of medicine, RA1-1270
Abstract

Abstract Objective This study aimed to explore psychosocial consequences of (false) positive liver screening results and to identify influencing factors for perceived strain within a multistage screening programme for liver cirrhosis and fibrosis in Germany. Methods Between June 2018 and May 2019, all positively screened patients were asked to participate in the study (n = 158). N = 11 telephone interviews and n = 4 follow‐up interviews were conducted. Semi‐structured telephone interviews were carried out. The analysis followed a structuring content analysis approach. Thereby, categories were first defined deductively. Second, the categories were revised inductively based on the data. Results The main themes found regarding the consequences of the screening were categorised in emotional reactions and behavioural reactions. Few respondents described negative emotional consequences related to screening. Those seem to be mostly driven by suboptimal patient–provider communication and might be worsened when transparent information transfer fails to happen. As a result, patients sought information and support in their social environment. All patients reported positive attitudes towards liver screening. Conclusion To reduce the potential occurrence of psychosocial consequences during the screening process, medical screening should be performed in the context of transparent information. Regular health communication on the side of health professionals and increasing patients' health literacy might contribute to avoiding negative emotions in line with screening. Patient or Public Contribution This study recognises the wide‐ranging patients' perspectives regarding the consequences of liver screening which should be taken into consideration when implementing a new screening programme to ensure a patient‐centred approach.

Published
2023
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5. Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice

Author

Sen Qiao, Samer Alasmi, Amanda Wyatt, Philipp Wartenberg, Hongmei Wang, Michael Candlish, Debajyoti Das, Mari Aoki, Ramona Grünewald, Ziyue Zhou, Qinghai Tian, Qiang Yu, Viktoria Götz, Anouar Belkacemi, Ahsan Raza, Fabien Ectors, Kathrin Kattler, Gilles Gasparoni, Jörn Walter, Peter Lipp, Patrice Mollard, Daniel J. Bernard, Ersin Karatayli, Senem Ceren Karatayli, Frank Lammert, and Ulrich Boehm

Subjects
Science
Abstract

Gonadotropes in the pituitary secrete follicle-stimulating hormone and luteinizing hormone to control gonadal function and fertility, but whether they exert actions on extra-gonadal organs is not fully understood. Here the authors report that gonadotropes regulate liver steatosis independent of the ovaries in mice.

Published
2023
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6. TNF-related apoptosis-inducing ligand, interferon gamma-induced protein 10, and C-reactive protein in predicting the progression of SARS-CoV-2 infection: a prospective cohort study

Author

Sina A. Tegethoff, Guy Danziger, Dennis Kühn, Charlotte Kimmer, Thomas Adams, Lena Heintz, Carlos Metz, Katharina Reifenrath, Rebecca Angresius, Sebastian Mang, Torben Rixecker, André Becker, Jürgen Geisel, Christophe Jentgen, Frederik Seiler, Matthias C. Reichert, Franziska Fröhlich, Sascha Meyer, Jürgen Rissland, Sebastian Ewen, Gudrun Wagenpfeil, Katharina Last, Sigrun Smola, Robert Bals, Frank Lammert, Sören L. Becker, Marcin Krawczyk, Philipp M. Lepper, and Cihan Papan

Subjects
COVID-19, Severity prediction, Host response, Biomarkers, TRAIL, IP-10, Infectious and parasitic diseases, RC109-216
Abstract

ABSTRACT: Background: Early prognostication of COVID-19 severity will potentially improve patient care. Biomarkers, such as TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10), and C-reactive protein (CRP), might represent possible tools for point-of-care testing and severity prediction. Methods: In this prospective cohort study, we analyzed serum levels of TRAIL, IP-10, and CRP in patients with COVID-19, compared them with control subjects, and investigated the association with disease severity. Results: A total of 899 measurements were performed in 132 patients (mean age 64 years, 40.2% females). Among patients with COVID-19, TRAIL levels were lower (49.5 vs 87 pg/ml, P = 0.0142), whereas IP-10 and CRP showed higher levels (667.5 vs 127 pg/ml, P

Published
2022
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7. LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Author

Isabel Graupera, Maja Thiele, Ann T. Ma, Miquel Serra-Burriel, Judit Pich, Núria Fabrellas, Llorenç Caballeria, Robert J. de Knegt, Ivica Grgurevic, Mathias Reichert, Dominique Roulot, Jörn M. Schattenberg, Juan M. Pericas, Paolo Angeli, Emmanuel A. Tsochatzis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosa M. Morillas, Rosario Hernández, Jordi Hoyo, Matilde Fuentes, Anita Madir, Adrià Juanola, Anna Soria, Marta Juan, Marta Carol, Alba Diaz, Sönke Detlefsen, Pere Toran, Guillem Pera, Céline Fournier, Anne Llorca, Phillip N. Newsome, Michael Manns, Harry J. de Koning, Feliu Serra-Burriel, Fernando Cucchietti, Anita Arslanow, Marko Korenjak, Laurens van Kleef, Josep Lluis Falcó, Patrick S. Kamath, Tom H. Karlsen, Laurent Castera, Frank Lammert, Aleksander Krag, Pere Ginès, and for the LiverScreen Consortium investigators

Subjects
Cirrhosis, Screening, Liver fibrosis, Chronic liver disease, NAFLD, NASH, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Published
2022
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8. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Author

Hamish Innes, Hans Dieter Nischalke, Indra Neil Guha, Karl Heinz Weiss, Will Irving, Daniel Gotthardt, Eleanor Barnes, Janett Fischer, M. Azim Ansari, Jonas Rosendahl, Shang‐Kuan Lin, Astrid Marot, Vincent Pedergnana, Markus Casper, Jennifer Benselin, Frank Lammert, John McLauchlan, Philip L. Lutz, Victoria Hamill, Sebastian Mueller, Joanne R. Morling, Georg Semmler, Florian Eyer, Johann von Felden, Alexander Link, Arndt Vogel, Jens U. Marquardt, Stefan Sulk, Jonel Trebicka, Luca Valenti, Christian Datz, Thomas Reiberger, Clemens Schafmayer, Thomas Berg, Pierre Deltenre, Jochen Hampe, Felix Stickel, and Stephan Buch

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol‐3‐phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol‐related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case‐control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP‐HCV), and one alcohol‐related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed‐effect meta‐analysis was used to determine the pooled effect size across all data sets. Across four case‐control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61‐0.84; P = 2.9 × 10−5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45‐2.86; P = 3.1 × 10−6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90‐1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84‐1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

Published
2022
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9. MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis

Author

Maciej K. Janik, Wiktor Smyk, Beata Kruk, Benedykt Szczepankiewicz, Barbara Górnicka, Magdalena Lebiedzińska-Arciszewska, Yaiza Potes, Inês C. M. Simões, Susanne N. Weber, Frank Lammert, Mariusz R. Więckowski, Piotr Milkiewicz, and Marcin Krawczyk

Subjects
Medicine, Science
Abstract

Abstract The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P

Published
2021
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10. Correction: LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Author

Isabel Graupera, Maja Thiele, Ann T. Ma, Miquel Serra-Burriel, Judit Pich, Núria Fabrellas, Llorenç Caballeria, Robert J. de Knegt, Ivica Grgurevic, Mathias Reichert, Dominique Roulot, Jörn M. Schattenberg, Juan M. Pericas, Paolo Angeli, Emmanuel A. Tsochatzis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosa M. Morillas, Rosario Hernández, Jordi Hoyo, Matilde Fuentes, Anita Madir, Adrià Juanola, Anna Soria, Marta Juan, Marta Carol, Alba Diaz, Sönke Detlefsen, Pere Toran, Guillem Pera, Céline Fournier, Anne Llorca, Phillip N. Newsome, Michael Manns, Harry J. de Koning, Feliu Serra-Burriel, Fernando Cucchietti, Anita Arslanow, Marko Korenjak, Laurens van Kleef, Josep Lluis Falcó, Patrick S. Kamath, Tom H. Karlsen, Laurent Castera, Frank Lammert, Aleksander Krag, Pere Ginès, and for the LiverScreen Consortium investigators

Subjects
Public aspects of medicine, RA1-1270
Published
2023
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11. Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand

Author

Wenjuan Yang, Andreas Denger, Caroline Diener, Frederic Küppers, Leticia Soriano-Baguet, Gertrud Schäfer, Archana K. Yanamandra, Renping Zhao, Arne Knörck, Eva C. Schwarz, Martin Hart, Frank Lammert, Leticia Prates Roma, Dirk Brenner, Grigorios Christidis, Volkhard Helms, Eckart Meese, Markus Hoth, and Bin Qu

Subjects
High glucose, CTLs, TRAIL, ROS, PI3K-Akt, NFκB, Immunologic diseases. Allergy, RC581-607
Abstract

TNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis. Our work suggests that HG-induced TRAILhigh CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.

Published
2022
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12. Liver stiffness as surrogate parameter in emergency assessment for inpatient health care utilization.

Author

Dominic Kaddu-Mulindwa, Marius von Martial, Angela Thiel-Bodenstaff, Vadim Lesan, Sebastian Ewen, Felix Mahfoud, Frank Lammert, and Marcin Krawczyk

Subjects
Medicine, Science
Abstract

BackgroundTransient elastography (TE) allows non-invasive quantification of liver stiffness (LSM) and steatosis (controlled attenuation parameter, CAP). Here we test the feasibility and utility of TE in the emergency department (ED) and investigate whether LSM predicts longer hospitalization and reimbursement for non-elective patients.MethodsLSM and CAP were determined in prospectively recruited consecutive adult patients admitted to the ED of a tertiary referral center. Patients were stratified according to the 9.1 kPa and 13.0 kPa LSM cut-offs. Elastography measurements were correlated with clinical and outcome parameters, including duration of hospital stay and hospitalization costs.ResultsIn 200 ED patients (133 men, age 18 - 97 years), median LSM was 5.5 kPa (2.4 - 69.1 kPa), and median CAP was 252 dB/m (100 - 400 dB/m). In total, 39 patients (19.5%) presented with LSM ≥ 9.1 kPa, and 24 patients (12.0%) presented with LSM ≥ 13.0 kPa. Heart failure (n = 19) was associated with higher LSM (p = 0.045). Patients with LSM ≥ 9.1 kPa were significantly (p < 0.01) more likely to require longer hospitalization than those with lower LSM. Patients with LSM ≥ 13.0 kPa generated significantly (p = 0.001) higher costs as compared to patients with low LSM.ConclusionsTransient elastography represents an easily accessible screening tool in ED that might help identify patients in need of increased health care resources.

Published
2022
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13. A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B

Author

Florian van Bömmel, Kerstin Stein, Renate Heyne, Jörg Petersen, Peter Buggisch, Christoph Berg, Stefan Zeuzem, Andreas Stallmach, Martin Sprinzl, Eckart Schott, Anita Pathil-Warth, Ulrike von Arnim, Verena Keitel, Jürgen Lohmeyer, Karl-Georg Simon, Christian Trautwein, Andreas Trein, Dietrich Hüppe, Markus Cornberg, Frank Lammert, Patrick Ingiliz, Reinhart Zachoval, Holger Hinrichsen, Alexander Zipprich, Hartmuth Klinker, Julian Schulze zur Wiesch, Anett Schmiedeknecht, Oana Brosteanu, and Thomas Berg

Subjects
Hepatology
Published
2023

16. Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL

Author

Christian Labenz, Anita Arslanow, Marc Nguyen-Tat, Michael Nagel, Marcus-Alexander Wörns, Matthias Christian Reichert, Franz Josef Heil, Dagmar Mainz, Gundula Zimper, Barbara Römer, Harald Binder, Erik Farin-Glattacker, Urs Fichtner, Erika Graf, Dominikus Stelzer, Reyn Van Ewijk, Julia Ortner, Louis Velthuis, Frank Lammert, and Peter R. Galle

Subjects
Liver Cirrhosis, Hepatology, Platelet Count, Humans, Alanine Transaminase, Aspartate Aminotransferases, Prospective Studies, Fibrosis, Biomarkers
Abstract

Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible.SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 ("Check-up 35") at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score0.5 were referred to a liver expert in secondary and/or tertiary care.A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83‰ vs. 3.36‰). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51‰, controls: 2.21‰).The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program.DRKS00013460 LAY SUMMARY: Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the 'SEAL' pathway represents a feasible and potentially cost-effective screening program.

Published
2022

18. Common variant p. <scp>D</scp> 19 <scp>H</scp> of the hepatobiliary sterol transporter <scp> ABCG8 </scp> increases the risk of gallstones in children

Author

Marcin Krawczyk, Olga Niewiadomska, Irena Jankowska, Krzysztof Jankowski, Sebastian Więckowski, Dariusz Lebensztejn, Sabina Więcek, Jolanta Gozdowska, Zbigniew Kułaga, Susanne N. Weber, Dieter Lütjohann, Frank Lammert, and Piotr Socha

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Hepatology, ATP Binding Cassette Transporter, Subfamily G, Member 8, Membrane Transport Proteins, Phytosterols, Gallstones, Middle Aged, Sterols, Cholesterol, Humans, ATP-Binding Cassette Transporters, Genetic Predisposition to Disease, Child, Aged
Abstract

Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter ABCG8 p.D19H and Gilbert UGT1A1*28 variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown.Overall, 214 children with gallstone disease (1 month-17 years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6-17 years, 115 boys) and 172 adults (age 40-92 years, 70 men) without gallstones. The ABCG8 p.D19H and UGT1A1*28 polymorphisms as well as ABCB4 (c.504CT rs1202283, c.711AT rs2109505) and NPC1L1 variants (p.V1296V rs217434, c.-18CA rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography/mass spectrometry.The ABCG8 risk allele was associated with an increased risk of stones (OR = 1.82, p = .03). Children carrying the p.19H allele presented with lower serum concentrations of surrogate markers of intestinal cholesterol absorption and decreased ratios of phytosterols to the cholesterol precursor desmosterol. Carriers of the common NPC1L1 rs217434 allele had an increased gallstone risk compared with stone-free adults (OR 1.90, p .01). This variant also affected the ratio of phytosterols to cholesterol precursors (p = .03). Other tested variants were not associated with gallstone risk.The p.D19H ABCG8 and, to a lesser extent, NPC1L1 rs217434 variants increase the risk of early-onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults.

Published
2022

20. Altered Expression of Antimicrobial Peptides in the Upper Gastrointestinal Tract of Patients with Diabetes Mellitus

Author

Oliver Linn, Bernhard Menges, Frank Lammert, Susanne N. Weber, and Marcin Krawczyk

Subjects
Nutrition and Dietetics, insulin resistance, cathelicidin, LL-37, defensin, Food Science, AMP
Abstract

Antimicrobial peptides (AMP) are essential components of innate immunity with a broad range of antimicrobial activities against bacteria, viruses, and fungi. The aim of this study was to investigate AMP expression in the upper gastrointestinal tract in normal and pathological metabolic states in humans. Furthermore, we examined the correlation between vitamin D levels and AMP expression in the same cohort. Serum concentrations of 25-hydroxyvitamin D3 were measured, and mRNA expression of β-defensins HBD-1, -2, -3, -4, α-defensins HD-5 and -6 and cathelicidin in the upper gastrointestinal tract epithelia were determined by quantitative RT-PCR in 31 individuals (10 with type 2 diabetes, 10 with insulin resistance, and 11 healthy controls). The majority of the cohort showed low vitamin D concentrations, which were negatively correlated with mRNA expression levels of HBD-3 in corpus mucosa. HBD-1 and HBD-3 mRNA were expressed in corpus mucosa, with the former significantly decreased in patients with diabetes. Hence, we conclude that type 2 diabetes is associated with reduced AMP expression in the upper gastrointestinal tract, which might contribute towards epithelial barrier dysfunction and increased bacterial translocation in these patients.

Published
2023
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21. Costs of a structured early detection program for advanced liver fibrosis and cirrhosis: insights on the 'plus' of Check-up 35+

Author

Julia Ortner, Reyn Joris Van Ewijk, Louis Velthuis, Christian Labenz, Anita Arslanow, Marcus-Alexander Wörns, Matthias Christian Reichert, Erik Farin-Glattacker, Urs Alexander Fichtner, Dominikus Stelzer, Peter Robert Galle, and Frank Lammert

Subjects
Gastroenterology
Abstract

Background The implementation of an early detection program for liver cirrhosis in a general population has been discussed for some time. Recently, the effectiveness of a structured screening procedure, called SEAL (Structured Early detection of Asymptomatic Liver cirrhosis), using liver function tests (AST and ALT) and APRI to early detect advanced fibrosis and cirrhosis in participants of the German “Check-up 35” was investigated. Methods This study identifies the expected diagnostic costs of SEAL in routine care and their drivers and reports on prevailing CLD etiologies in this check-up population. The analysis is based on theoretical unit costs, as well as on the empirical billing and diagnostic data of SEAL participants. Results Screening costs are mainly driven by liver biopsies, which are performed in a final step in some patients. Depending on the assumed biopsy rates and the diagnostic procedure, the average diagnostic costs are between EUR 5.99 and 13.74 per Check-up 35 participant and between EUR 1,577.06 and 3,620.52 per patient diagnosed with fibrosis/cirrhosis (F3/F4). The prevailing underlying etiology in 60% of cases is non-alcoholic fatty liver disease. Discussion A liver screening following the SEAL algorithm could be performed at moderate costs. Screening costs in routine care depend on actual biopsy rates and procedures, attendance rates at liver specialists, and the prevalence of fibrosis in the Check-up 35 population. The test for viral hepatitis newly introduced to Check-up 35 as once-in-a-lifetime part of Check-up 35 is no alternative to SEAL.

Published
2023

24. A mixed-methods study to define Textbook Outcome for the treatment of patients with uncomplicated symptomatic gallstone disease with hospital variation analyses in Dutch trial data

Author

Floris M. Thunnissen, Daan J. Comes, Carmen S.S. Latenstein, Martijn W.J. Stommel, Cornelis J.H.M. van Laarhoven, Joost P.H. Drenth, Marten A. Lantinga, Femke Atsma, Philip R. de Reuver, Quirijn A.J. Eijsbouts, Joos Heisterkamp, Djamila Boerma, M.J. Jennifer, Peter van Duivendijk, Bastiaan Wiering, Marja A. Boermeester, Gwen Diepenhorst, Jarmila van der Bilt, Otmar Buyne, Niels G. Venneman, Daniel Keszthelyi, Ifran Ahmed, Thomas J. Hugh, Stephen J. Wigmore, Steven M. Strasberg, Ewen M. Harrison, Frank Lammert, Kurinchi Gurusamy, Dimitros Moris, Kjetil Soreide, Theodore N. Pappas, Vinay K. Kapoor, Antonia Speelman, and Chris van den Brink

Subjects
Hepatology, Gastroenterology
Abstract

Background: International consensus on the ideal outcome for treatment of uncomplicated symptomatic gallstone disease is absent. This mixed-method study defined a Textbook Outcome (TO) for this large group of patients. Methods: First, expert meetings were organised with stakeholders to design the survey and identify possible outcomes. To reach consensus, results from expert meetings were converted in a survey for clinicians and for patients. During the final expert meeting, clinicians and patients discussed survey outcomes and a definitive TO was formulated. Subsequently, TO-rate and hospital variation were analysed in Dutch hospital data from patients with uncomplicated gallstone disease. Results: First expert meetings returned 32 outcomes. Outcomes were distributed in a survey among 830 clinicians from 81 countries and 645 Dutch patients. Consensus-based TO was defined as no more biliary colic, no biliary and surgical complications, and the absence or reduction of abdominal pain. Analysis of individual patient data showed that TO was achieved in 64.2% (1002/1561). Adjusted-TO rates showed modest variation between hospitals (56.6-74.9%). Conclusion: TO for treatment of uncomplicated gallstone disease was defined as no more biliary colic, no biliary and surgical complications, and absence or reduction of abdominal pain.TO may optimise consistent outcome reporting in care and guidelines for treating uncomplicated gallstone disease.

Published
2023

27. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases

Author

Harry J. de Koning, Ivica Grgurević, Patrick S. Kamath, Laurent Castera, Emmanuel Tsochatzis, Frank Lammert, Isabel Graupera, Ann T. Ma, Núria Fabrellas, Dominique Roulot, Pere Ginès, Mª Alba Diaz, Salvador Augustin, Andrea Martini, Vincent Wai-Sun Wong, Judit Pich, Rosa Maria Morillas, Philip N. Newsome, Miquel Serra-Burriel, Maja Thiele, Aleksander Krag, Phillipp Hartmann, Robert J. de Knegt, Michael P Manns, Montserrat García-Retortillo, Jörn M. Schattenberg, Indra Neil Guha, Alina M. Allen, Llorenç Caballería, Institut Català de la Salut, [Ginès P, Graupera I] Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain. August Pi I Sunyer Biomedical Research Institute, Barcelona, Spain. Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain. Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Castera L] Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. Université de Paris, Paris, France. Inserm UMR 1149, Centre de Recherche Sur L'inflammation, Paris, France. [Lammert F] Department of Medicine II, Saarland University Medical Center, Homburg, Germany. Institute for Occupational Medicine and Public Health, Saarland University, Homburg, Germany. Health Sciences, Hannover Medical School, Hannover, Germany. [Serra-Burriel M] Epidemiology, Statistics, and Prevention Institute, University of Zurich, Zurich, Switzerland. [Allen AM] Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA. [Salvador A] Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain. Unitat Hepàtica, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrosi hepàtica - Diagnòstic, Cirrhosis, Fibrosi, Biopsy, enfermedades del sistema digestivo::enfermedades hepáticas::cirrosis hepática [ENFERMEDADES], Population, Digestive System Diseases::Liver Diseases::Liver Cirrhosis [DISEASES], Otros calificadores::/diagnóstico [Otros calificadores], Disease, Fetge -- Malalties, Diagnosis::Diagnostic Techniques and Procedures::Mass Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Asymptomatic, Gastroenterology, Global Burden of Disease, Liver disease, Hepatitis B, Chronic, SDG 3 - Good Health and Well-being, Liver Function Tests, Non-alcoholic Fatty Liver Disease, Risk Factors, Fibrosis, Internal medicine, Prevalence, Cribatge (Medicina), Other subheadings::/diagnosis [Other subheadings], diagnóstico::técnicas y procedimientos diagnósticos::cribado sistemático [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Humans, Mass Screening, Medicine, education, liver fibrosis, education.field_of_study, Hepatology, business.industry, Fatty liver, Cirrosi, Hepatitis C, Chronic, medicine.disease, Early Diagnosis, Liver, Disease Progression, Elasticity Imaging Techniques, medicine.symptom, Transient elastography, business
Abstract

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)

Published
2021

28. Screening for fibrosis to diagnose liver diseases early

Author

Pere Ginès, Maja Thiele, Isabel Graupera, Miquel Serra-Burriel, Robert J. de Knegt, Frank Lammert, Laurent Castera, Marko Korenjak, Patrick S. Kamath, Ivica Grgurević, Salvatore Piano, Núria Fabrellas, Anita Arslanow, Aleksander Krag, and Gastroenterology & Hepatology

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology
Published
2023

29. Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19

Author

Christian Herr, Dominic Eisinger, Thomas Volk, Guy Danziger, Sabrina I. Hörsch, Michael Kindermann, Sigrun Smola, Robert Bals, Bahareh Mozafari, Martina Seibert, Florian Custodis, Daniel Grandt, Philipp M. Lepper, Sanjay Kumar Srikakulam, Constantin Marcu, Konrad Schwarzkopf, Rolf Müller, Marcin Krawczyk, Zuhair Wolf Dietrich Ataya, Harald Schäfer, Gudrun Wagenpfeil, Felix Ritzmann, Kai Eltges, Frank Lammert, Katharina Günther, Thimoteus Speer, Marc Mittag, Andreas Keller, Christoph Beisswenger, Thomas Adams, Michael Zemlin, Sebastian Mang, and HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.

Subjects
medicine.medical_specialty, Decorin, Immunology, Inflammation, RM1-950, Disease, MMP7, Internal medicine, Pathology, RB1-214, Immunology and Allergy, Medicine, Multiplex, Original Research, business.industry, Venous blood, medicine.disease, Pneumonia, Respiratory failure, inflammation, SARS-CoV2, Biomarker (medicine), biomarker, Therapeutics. Pharmacology, medicine.symptom, Journal of Inflammation Research, business, Cytokine storm
Abstract

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

Published
2022
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30. The rs12532734 Polymorphism Near the Solute Carrier 26A3 Gene Locus Is Associated With Gallstone Disease in Children

Author

Marcin Krawczyk, Olga Niewiadomska, Irena Jankowska, Krzysztof Jankowski, Jolanta Świderska, Dariusz Lebensztejn, Sabina Więcek, Jolanta Gozdowska, Zbigniew Kułaga, Susanne N. Weber, Frank Lammert, and Piotr Socha

Subjects
Adult, Polymorphism, Genetic, Ursodeoxycholic Acid, Gastroenterology, RNA-Binding Proteins, Gallstones, Bicarbonates, Sulfate Transporters, Pediatrics, Perinatology and Child Health, Humans, Cholecystectomy, Chloride-Bicarbonate Antiporters, Child, Genome-Wide Association Study
Abstract

Gallstones are increasingly frequent in children. In this candidate gene study, we genotyped 5 gene variants ( ANO1 , SPTLC3 , TMEM147 , TNRC6B , rs12532734) from a recent gallstone genome-wide association study (GWAS) in a cohort of 214 children with gallstones and 172 gallstone-free adult controls. In total, 138 genotyped children presented with symptomatic gallstone disease, 47 underwent cholecystectomy, and 126 received ursodeoxycholic acid (UDCA) as therapy for stones. Among 5 tested variants, the rs12532734 polymorphism modulated the gallstone risk in the studied cohort. Its genotype distribution significantly ( P = 0.025) departed from the Hardy-Weinberg equilibrium among cases, and the common allele was associated with increased odds of developing gallstones at young age (OR = 1.69, P = 0.014). SLC26A3 is the nearest gene to rs12532734 and is involved in the transepithelial bicarbonate and chloride transport. The association of rs12532734 with pediatric gallstones is a novel finding warranting further investigations also with regard to biliary bicarbonate flux and bile composition.

Published
2022

32. Inside Front Cover

Author

Guido Stirnimann, Thomas Berg, Laurent Spahr, Stefan Zeuzem, Stuart McPherson, Frank Lammert, Federico Storni, Vanessa Banz, Jana Babatz, Victor Vargas, Andreas Geier, Cornelius Engelmann, Adam Herber, Claudia Trepte, Jeroen Capel, and Andrea De Gottardi

Subjects
Hepatology
Published
2022

34. Factors associated with an increased risk of SARS-CoV-2 infection in healthcare workers in aerosol-generating disciplines

Author

Christoph Römmele, Maria Kahn, Stephan Zellmer, Anna Muzalyova, Gertrud Hammel, Christina Bartenschlager, Albert Beyer, Jonas Rosendahl, Tilo Schlittenbauer, Johannes Zenk, Bilal Al-Nawas, Roland Frankenberger, Juergen Hoffmann, Christoph Arens, Frank Lammert, Claudia Traidl-Hoffmann, Helmut Messmann, and Alanna Ebigbo

Subjects
Gastroenterology, ddc:610
Abstract

Healthcare workers (HCWs) are at a high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate risk factors for SARS-CoV-2 infection among HCWs in medical disciplines with AGP.A nationwide questionnaire-based study in private practices and hospital settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCWs and potential risk factors of infection were investigated.2070 healthcare facilities with 25113 employees were included in the study. The overall infection rate among HCWs was 4.7%. Multivariate analysis showed that regions with higher incidence rates had a significantly increased risk of infection. Furthermore, hospital setting and HCWs in gastrointestinal endoscopy (GIE) had more than double the risk of infection (OR 2.63; 95% CI 2.50-2.82, p0.01 and OR 2.35; 95% CI 2.25-2.50, p0.01). For medical facilities who treated confirmed SARS-CoV-2 cases, there was a tendency towards higher risk of infection (OR 1.39; 95% CI 1.11-1.63, p=0.068).Both factors within and outside medical facilities appear to be associated with an increased risk of infection among HCWs. Therefore, GIE and healthcare delivery setting were related to increased infection rates. Regions with higher SARS-CoV-2 incidence rates were also significantly associated with increased risk of infection.Medizinisches Personal ist durch die Exposition gegenüber potenziell infektiösem Material einem erhöhten Infektionsrisiko ausgesetzt. Dies gilt insbesondere für Fachdisziplinen mit aerosolgenerierenden Prozeduren (AGP). Hierfür gibt es jedoch kaum Daten, insbesondere für den ambulanten Versorgungssektor. Ziel dieser Studie war es, die Häufigkeit sowie potenzielle Risikofaktoren für SARS-CoV-2-Infektionen bei medizinischem Personal von aerosolgenerierenden Disziplinen zu erheben und zu identifizieren.Zwischen dem 16.12.2020 und 24.01.2021 wurde eine bundesweite Umfrage in den Disziplinen der gastrointestinalen Endoskopie (GIE); Hals-, Nasen-, Ohrenheilkunde (HNO); Mund-, Kiefer-, Gesichtschirurgie (MKG) und der Zahn-, Mund-, Kieferheilkunde (ZMK) durchgeführt. Hierbei wurden Daten zu SARS-CoV-2-Infektionen beim medizinischen Personal sowie potenzielle Risikofaktoren erfasst.25113 Beschäftigte in 2070 Einrichtungen wurden in die Studie eingeschlossen. Die Gesamtinfektionsrate unter dem medizinischen Personal betrug 4,7 %. Die multivariate Analyse zeigte, dass Regionen mit höheren Inzidenzraten ein deutlich erhöhtes Infektionsrisiko aufwiesen. Außerdem war das Infektionsrisiko in Krankenhäusern und bei Beschäftigten der GIE um mehr als das Zweifache erhöht (OR 2,63; p0,01 und OR 2,35; p0,01). Ein tendenziell erhöhtes Infektionsrisiko bestand in Einrichtungen, die bestätigte SARS-CoV-2-Fälle behandelt haben (OR 1,39; p=0,068).Das SARS-CoV-2-Infektionsrisiko für medizinisches Personal wird sowohl von Faktoren innerhalb als auch Faktoren außerhalb von medizinischen Einrichtungen bestimmt. Die Fachrichtung der GIE sowie die Tätigkeit in einem Krankenhaus beeinflussen signifikant die Infektionsraten. Eine höhere SARS-CoV-2-Inzidenzrate in der Region geht ebenfalls mit einem signifikant erhöhten Infektionsrisiko einher.

Published
2022

35. Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers

Author

Mattias Mandorfer, Nadine T. Gaisa, Christian Trautwein, Jef Verbeek, Helmut Denk, Daniel Neureiter, Elmar Aigner, Julia Kümpers, Heinz Zoller, Barbara Burbaum, LS Moeller, Heike Bantel, Olivier Govaere, Federica Benini, Joanna Chorostowska-Wynimko, Aleksander Krag, Frank Lammert, Jacob George, Katharina Wöran, Thomas Reiberger, Georg Lurje, Marla Gutberlet, Felix Stickel, Lisa Bewersdorf, Michael Trauner, Mohammed Eslam, V Woditsch, Sabina Janciauskiene, Tania Roskams, V Pereira, Johannes Haybaeck, J. Voss, Karim Hamesch, C Lindhauer, Annika Gross, Andreas Geier, Mònica Pons, Malin Fromme, Alexander Teumer, Quentin M. Anstee, Joan Genescà, Matthias C. Reichert, Biaohuan Zhou, Pawel Kuca, Marcin Krawczyk, Carolin V. Schneider, Pavel Strnad, Timm Dirrichs, Christian Datz, Joana Carvão, Robert Bals, Frederik Nevens, and Benedikt Schäfer

Subjects
Adult, Counseling, Liver Cirrhosis, Male, 0301 basic medicine, Heterozygote, medicine.medical_specialty, Cirrhosis, ALT, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Liver Function Tests, alpha 1-Antitrypsin Deficiency, Internal medicine, Genotype, medicine, Humans, Longitudinal Studies, Prospective Studies, Risk factor, Aged, Alpha 1-antitrypsin deficiency, Hepatology, business.industry, Homozygote, Odds ratio, Middle Aged, medicine.disease, United Kingdom, GGT, Cross-Sectional Studies, Phenotype, Fibroscan, 030104 developmental biology, Liver, alpha 1-Antitrypsin, Cohort, Elasticity Imaging Techniques, Female, SERPINA1, 030211 gastroenterology & hepatology, Transient elastography, business
Abstract

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

Published
2022
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36. SARS-CoV-2 vaccination rate and SARS-CoV-2 infection of health care workers in aerosol-generating medical disciplines

Author

Anna Muzalyova, Alanna Ebigbo, Maria Kahn, Stephan Zellmer, Albert Beyer, Jonas Rosendahl, Johannes Zenk, Bilal Al-Nawas, Roland Frankenberger, Juergen Hoffmann, Christoph Arens, Frank Lammert, Claudia Traidl-Hoffmann, Helmut Messmann, and Christoph Roemmele

Subjects
aerosol-generating procedures, SARS-CoV-2, perceived risk of infection, vaccination rate, General Medicine, ddc:610
Abstract

Healthcare workers (HCW) who perform aerosol-generating procedures (AGP) are at high risk of SARS-CoV-2 infection. Data on infection rates and vaccination are limited. A nationwide, cross-sectional study focusing on AGP-related specialties was conducted between 3 May 2021 and 14 June 2021. Vaccination rates among HCW, perception of infection risk, and infection rates were analyzed, focusing on the comparison of gastrointestinal endoscopy (GIE) and other AGP-related specialties (NON-GIE), from the beginning of the pandemic until the time point of the study. Infections rates among HCW developed similarly to the general population during the course of the pandemic, however, with significantly higher infections rates among the GIE specialty. The perceived risk of infection was distributed similarly among HCW in GIE and NON-GIE (91.7%, CI: 88.6–94.4 vs. 85.8%, CI: 82.4–89.0; p < 0.01) with strongest perceived threats posed by AGPs (90.8%) and close patient contact (70.1%). The very high vaccination rate (100–80%) among physicians was reported at 83.5%, being significantly more frequently reported than among nurses (56.4%, p < 0.01). GIE had more often stated very high vaccination rate compared with NON-GIE (76.1% vs. 65.3%, p < 0.01). A significantly higher rate of GIE was reported to have fewer concerns regarding infection risk after vaccination than NON-GIE (92.0% vs. 80.3%, p < 0.01).

Published
2022

37. S3-Guideline: Diagnosis and Therapy of Hepatocellular Carcinoma

Author

Sabrina, Voesch, Michael, Bitzer, Joerg, Albert, Peter, Bartenstein, Wolf, Bechstein, Susanne, Bloedt, Thomas, Brunner, Frank, Dombrowski, Matthias, Evert, Markus, Follmann, Christian, La Fougere, Paul, Freudenberger, Andreas, Geier, Eleni, Gkika, Martin, Goetz, Elke, Hammes, Thomas, Helmberger, Ralf-Thorsten, Hoffmann, Wolf-Peter, Hofmann, Peter, Huppert, Achim, Kautz, Gabi, Knoetgen, Juergen, Koerber, David, Krug, Frank, Lammert, Hauke, Lang, Thomas, Langer, Philipp, Lenz, Andreas, Mahnken, Alexander, Meining, Oliver, Micke, Silvio, Nadalin, Johann, Ockenga, Karl-Juergen, Oldhafer, Philipp, Paprottka, Kerstin, Paradies, Philippe, Pereira, Thorsten, Persigehl, Mathias, Plauth, Ruben, Plentz, Juergen, Pohl, Jutta, Riemer, Peter, Reimer, Johanna, Ringwald, Ulrike, Ritterbusch, Elke, Roeb, Barbara, Schellhaas, Peter, Schirmacher, Irene, Schmid, Andreas, Schuler, Dietrich, von Schweinitz, Daniel, Seehofer, Marianne, Sinn, Alexander, Stein, Andreas, Stengel, Nadine, Steubesand, Christian, Stoll, Andrea, Tannapfel, Anne, Taubert, Joerg, Trojan, Ingo, van Thiel, Reina, Tholen, Arndt, Vogel, Thomas, Vogl, Hilke, Vorwerk, Frank, Wacker, Oliver, Waidmann, Heiner, Wedemeyer, Henning, Wege, Dane, Wildner, Christian, Wittekind, Marcus-Alexander, Worns, Peter, Galle, Nisar, Malek, Sabrina, Voesch, Michael, Bitzer, Joerg, Albert, Peter, Bartenstein, Wolf, Bechstein, Susanne, Bloedt, Thomas, Brunner, Frank, Dombrowski, Matthias, Evert, Markus, Follmann, Christian, La Fougere, Paul, Freudenberger, Andreas, Geier, Eleni, Gkika, Martin, Goetz, Elke, Hammes, Thomas, Helmberger, Ralf-Thorsten, Hoffmann, Wolf-Peter, Hofmann, Peter, Huppert, Achim, Kautz, Gabi, Knoetgen, Juergen, Koerber, David, Krug, Frank, Lammert, Hauke, Lang, Thomas, Langer, Philipp, Lenz, Andreas, Mahnken, Alexander, Meining, Oliver, Micke, Silvio, Nadalin, Johann, Ockenga, Karl-Juergen, Oldhafer, Philipp, Paprottka, Kerstin, Paradies, Philippe, Pereira, Thorsten, Persigehl, Mathias, Plauth, Ruben, Plentz, Juergen, Pohl, Jutta, Riemer, Peter, Reimer, Johanna, Ringwald, Ulrike, Ritterbusch, Elke, Roeb, Barbara, Schellhaas, Peter, Schirmacher, Irene, Schmid, Andreas, Schuler, Dietrich, von Schweinitz, Daniel, Seehofer, Marianne, Sinn, Alexander, Stein, Andreas, Stengel, Nadine, Steubesand, Christian, Stoll, Andrea, Tannapfel, Anne, Taubert, Joerg, Trojan, Ingo, van Thiel, Reina, Tholen, Arndt, Vogel, Thomas, Vogl, Hilke, Vorwerk, Frank, Wacker, Oliver, Waidmann, Heiner, Wedemeyer, Henning, Wege, Dane, Wildner, Christian, Wittekind, Marcus-Alexander, Worns, Peter, Galle, and Nisar, Malek

Published
2022

38. Genetic variation in

Author

Stephan, Buch, Hamish, Innes, Philipp Ludwig, Lutz, Hans Dieter, Nischalke, Jens U, Marquardt, Janett, Fischer, Karl Heinz, Weiss, Jonas, Rosendahl, Astrid, Marot, Marcin, Krawczyk, Markus, Casper, Frank, Lammert, Florian, Eyer, Arndt, Vogel, Silke, Marhenke, Johann, von Felden, Rohini, Sharma, Stephen Rahul, Atkinson, Andrew, McQuillin, Jacob, Nattermann, Clemens, Schafmayer, Andre, Franke, Christian, Strassburg, Marcella, Rietschel, Heidi, Altmann, Stefan, Sulk, Veera Raghavan, Thangapandi, Mario, Brosch, Carolin, Lackner, Rudolf E, Stauber, Ali, Canbay, Alexander, Link, Thomas, Reiberger, Mattias, Mandorfer, Georg, Semmler, Bernhard, Scheiner, Christian, Datz, Stefano, Romeo, Stefano, Ginanni Corradini, William Lucien, Irving, Joanne R, Morling, Indra Neil, Guha, Eleanor, Barnes, M Azim, Ansari, Jocelyn, Quistrebert, Luca, Valenti, Sascha A, Müller, Marsha Yvonne, Morgan, Jean-François, Dufour, Jonel, Trebicka, Thomas, Berg, Pierre, Deltenre, Sebastian, Mueller, Jochen, Hampe, and Felix, Stickel

Abstract

Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis.Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina).Associations with variants rs738409 inThis study identifies rs2242652 in

Published
2022

39. Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency

Author

Alice M Turner, David A. Lomas, Alexa Nuñez, Sabina Janciauskiene, William J.H. Griffiths, Christian Trautwein, Joan Genescà, Michael Trauner, John R. Hurst, Jef Verbeek, Matthias C. Reichert, Guilherme Macedo, Ravi Mahadeva, Mònica Pons, Aleksander Krag, Rui Gaspar, V Pereira, Heinz Zoller, Catarina Gomes, Mattias Mandorfer, Barbara Burbaum, Frank Lammert, V Woditsch, Paul Ellis, Aileen Marshall, Douglas Thorburn, Nadine T. Gaisa, Karim Hamesch, Joanna Chorostowska-Wynimko, Luís Jasmins, Malin Fromme, Rodrigo Liberal, Pavel Strnad, Frederik Nevens, Noel G. McElvaney, Marc Miravitlles, Virginia Clark, Bibek Gooptu, Benedikt Schaefer, Katrine Holtz Thorhauge, Carolin V. Schneider, Nelia Abreu, Kai Markus Schneider, Federica Benini, Fromme, Malin [0000-0003-0382-5705], Hamesch, Karim [0000-0002-1702-2746], Reichert, Matthias C [0000-0002-8192-0575], Mandorfer, Mattias [0000-0003-2330-0017], Gaspar, Rui [0000-0003-0332-3844], Trauner, Michael [0000-0002-1275-6425], Krag, Aleksander [0000-0002-9598-4932], Gooptu, Bibek [0000-0002-5223-1121], Hurst, John R [0000-0002-7246-6040], Lomas, David A [0000-0003-2339-6979], Strnad, Pavel [0000-0002-7122-6379], and Apollo - University of Cambridge Repository

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, liver cirrhosis, liver, Gastroenterology, Cohort Studies, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Cholelithiasis, Fibrosis, alpha 1-Antitrypsin Deficiency, Internal medicine, Diabetes mellitus, Genotype, Prevalence, medicine, Humans, cancer, Aged, Alpha 1-antitrypsin deficiency, business.industry, Liver Neoplasms, fibrosis, Cancer, Gallstones, Middle Aged, medicine.disease, United Kingdom, Phenotype, 030228 respiratory system, Case-Control Studies, Female, 030211 gastroenterology & hepatology, business
Abstract

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.

Published
2022

40. Variants APOE (rs429358) and TM6SF2 (rs187429064) modify the risk of hepatocellular carcinoma

Author

Hamish Innes, HansDieter Nischalke, KarlHeinz Weiss, Daniel Gotthardt, Neil Guha, Eleanor Barnes, Will Irving, Janett Fischer, Jonas Rosendahl, Markus Casper, Frank Lammert, PhilipL Lutz, Sebastian Mueller, Georg Semmler, Florian Eyer, Johann von Felden, Alexander Link, Arndt Vogel, JensU Marquardt, Stefan Sulk, Christian Datz, Thomas Reiberger, Clemens Schafmayer, Thomas Berg, Jochen Hampe, Felix Stickel, and Stephan Buch

Published
2022

46. Prognostic performance of the 'DICA' endoscopic classification and the 'CODA' score in predicting clinical outcomes of diverticular disease: an international, multicentre, prospective cohort study

Author

Antonio, Tursi, Giovanni, Brandimarte, Francesco, Di Mario, Walter, Elisei, Marcello, Picchio, Leonardo, Allegretta, Maria Laura, Annunziata, Mauro, Bafutto, Gabrio, Bassotti, Maria Antonietta, Bianco, Raffaele, Colucci, Rita, Conigliaro, Dan, Dumitrascu, Ricardo, Escalante, Luciano, Ferrini, Giacomo, Forti, Marilisa, Franceschi, Maria Giovanna, Graziani, Frank, Lammert, Giovanni, Latella, Giovanni, Maconi, Gerardo, Nardone, Lucia, Camara de Castro Oliveira, Enio, Chaves Oliveira, Alfredo, Papa, Savvas, Papagrigoriadis, Anna, Pietrzak, Stefano, Pontone, Tomas, Poskus, Giuseppe, Pranzo, Matthias Christian, Reichert, Stefano, Rodinò, Jaroslaw, Regula, Giuseppe, Scaccianoce, Franco, Scaldaferri, Roberto, Vassallo, Costantino, Zampaletta, Angelo, Zullo, Daniele, Piovani, Stefanos, Bonovas, Silvio, Danese, Paolo, Usai, Tursi, A., Brandimarte, G., Di Mario, F., Elisei, W., Picchio, M., Allegretta, L., Annunziata, M. L., Bafutto, M., Bassotti, G., Bianco, M. A., Colucci, R., Conigliaro, R., Dumitrascu, D., Escalante, R., Ferrini, L., Forti, G., Franceschi, M., Graziani, M. G., Lammert, F., Latella, G., Maconi, G., Nardone, G., Camara de Castro Oliveira, L., Chaves Oliveira, E., Papa, A., Papagrigoriadis, S., Pietrzak, A., Pontone, S., Poskus, T., Pranzo, G., Reichert, M. C., Rodino, S., Regula, J., Scaccianoce, G., Scaldaferri, F., Vassallo, R., Zampaletta, C., Zullo, A., Piovani, D., Bonovas, S., and Danese, S.

Subjects
medicine.medical_specialty, Prognosi, diverticular disease, Coda, Cohort Studies, Colonic, Internal medicine, Diverticulosis, Colonic, medicine, Humans, Prospective Studies, endoscopy, Prospective cohort study, Diverticuliti, Diverticulitis, Inflammation, Diverticular Diseases, Diverticulosis, medicine.diagnostic_test, business.industry, Colonoscopy, Prognosis, Diverticulum, Gastroenterology, medicine.disease, Endoscopy, Prospective Studie, Diverticular disease, Cohort Studie, business, Complication, Human, Cohort study
Abstract

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.

Published
2022

47. Global multi-stakeholder endorsement of the MAFLD definition

Author

Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. Lee, Way Seah Lee, Yeong Yeh Lee, Diana Julie Leeming, Nathalie Carvalho Leite, Roberto Leon, Cosmas Rinaldi Adithya Lesmana, Junfeng Li, Qiong Li, Jun Li, Yang-Yang Li, Yufang Li, Lei Li, Min Li, Yiling li, Huiqing Liang, Tang Lijuan, Seng Gee Lim, Lee-Ling Lim, Shumei Lin, Han-Chieh Lin, Rita Lin, Rania Lithy, Yaru Liu, Yuanyuan Liu, Xin Liu, Wen-Yue Liu, Shourong Liu, Ken Liu, Tian Liu, Amedeo Lonardo, Mariana Bravo López, Eva López-Benages, Patricio Lopez-Jaramillo, Huimin Lu, Lun Gen Lu, Yan Lu, John Lubel, Rashid Lui, Iulianna Lupasco, Elena Luzina, Xiao-Hui Lv, Kate Lynch, Hong-Lei Ma, Mariana Verdelho Machado, Nonso Maduka, Katerina Madzharova, Russellini Magdaong, Sanjiv Mahadeva, Amel Mahfouz, Nik Ritza Kosai Nik Mahmood, Eman Mahmoud, Mohamed Mahrous, Rakhi Maiwall, Ammar Majeed, Avik Majumdar, Loey Mak, Madiha M Maklouf, Reza Malekzadeh, Claudia Mandato, Alessandra Mangia, Jake Mann, Hala Hussien Mansour, Abdellah Mansouri, Alessandro Mantovani, Jun qian Mao, Flor Maramag, Giulio Marchesini, Claude Marcus, Rui António Rocha Tato Marinho, Maria L Martinez-Chantar, Antonieta A. Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. Nersesov, Manuela Neuman, Masolwa Ng'wanasayi, Yan Ni, Amanda Nicoll, Takashi Niizeki, Dafina Nikolova, Wang Ningning, Madunil Niriella, K.A Nogoibaeva, Rozeena Nordien, Catherine O Sullivan, James O'Beirne, Solomon Obekpa, Ponsiano Ocama, Missiani Ochwoto, Michael Promise Ogolodom, Olusegun Ojo, Nana Okrostsvaridze, Claudia P. Oliveira, Raul Contreras Omaña, Omneya M. Omar, Hanaa Omar, Mabroka Omar, Salma Omran, Reham Omran, Marian Muse Osman, Nevin Owise, Theobald Owusu-Ansah, P. Martín Padilla- Machaca, Sirish Palle, Ziyan Pan, Xiao-Yan Pan, Qiuwei Pan, Apostolis Papaefthymiou, Feliciano Chanana Paquissi, Gabriella Par, Arit Parkash, Diana Payawal, Kevork M. Peltekian, Xuebin Peng, Liang Peng, Ying Peng, Rahul Pengoria, Martina Perez, José Luis Pérez, Norma Marlene Pérez, Marcello Persico, Mário Guimarães Pessoa, Salvatore Petta, Mathew Philip, Maria Corina Plaz Torres, Naveen Polavarapu, Jaime Poniachik, Piero Portincasa, Chunwen Pu, Tuğrul Pürnak, Edhie Purwanto, Xiaolong Qi, Xingshun Qi, Zibing Qian, Zhao Qiang, Zengpei Qiao, Liang Qiao, Alberto Queiroz, Atoosa Rabiee, Manal Radwan, Alain Marcel Rahetilahy, Yasmin Ramadan, Dina Ramadan, Anis Safura Ramli, Grant A. Ramm, Ao Ran, Ivan Rankovic, Huiying RAO, Sara Raouf, Sayantan Ray, Nancy Reau, Ahmed Refaat, Thomas Reiberger, Jose M Remes-Troche, Eira Cerda Reyes, Ben Richardson, Ezequiel Ridruejo, Sergio Riestra Jimenez, Ibrahim Rizk, Stuart Roberts, Juan Pablo Roblero, Jorge Alberto Prado Robles, Don Rockey, Manuel Rodríguez, Heriberto Rodríguez Hernández, Eva Román, Fernando Gomes Romeiro, Stefano Romeo, Jose Miguel Rosales-Zabal, Georgina R. Roshdi, Natalia Rosso, Andres Ruf, Patricia Cordero Ruiz, Nelia R. Runes, Andrea Ruzzenente, Marno Ryan, Ahmed Saad, Eman BE Sabbagh, Meriam Sabbah, Shimaa Saber, Reham Sabrey, Ramy Sabry, Maysaa Abdallah Saeed, Dina Said, Ebada M Said, Mohammad Amin Sakr, Yara Salah, Rabab Maamoun Salama, Asmaa Salama, Hussein Saleh, Ahmed Saleh, Ahmed Salem, Ahmed Thabet Salem, Alkassoum Salifou, Aso Faeq Salih, Abdallah Salman, Hanen Samouda, Faisal Sanai, Juan Francisco Sánchez-Ávila, Lakshumanan Sanker, Tomoya Sano, Miquel Sanz, Tobokalova Saparbu, Rohit Sawhney, Fatma Sayed, Sayed A. Sayed, Ashraf Othman Sayed, Manar Sayed, Giada Sebastiani, Laura Secadas, Khawaja Qamaruddin Sediqi, Sameh Seif, Nady Semida, Ebubekir Şenateş, Elena Daniela Serban, Lawrence Serfaty, Wai-Kay Seto, Ikram Sghaier, Min Sha, Hamada M. Shabaan, Lobna Shalaby, Inass Shaltout, Ala I. 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Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease

Subjects
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract

Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)

Published
2022

49. S3-Leitlinie : Diagnostik und Therapie des hepatozellulären Karzinoms

Author

Sabrina, Voesch, Michael, Bitzer, Jörg, Albert, Peter, Bartenstein, Wolf, Bechstein, Susanne, Blödt, Thomas, Brunner, Frank, Dombrowski, Matthias, Evert, Markus, Follmann, Christian, La Fougère, Paul, Freudenberger, Andreas, Geier, Eleni, Gkika, Martin, Götz, Elke, Hammes, Thomas, Helmberger, Ralf-Thorsten, Hoffmann, Wolf-Peter, Hofmann, Peter, Huppert, Achim, Kautz, Gabi, Knötgen, Jürgen, Körber, David, Krug, Frank, Lammert, Hauke, Lang, Thomas, Langer, Philipp, Lenz, Andreas, Mahnken, Alexander, Meining, Oliver, Micke, Silvio, Nadalin, HuuPhuc, Nguyen, Johann, Ockenga, Karl-Jürgen, Oldhafer, Philipp, Paprottka, Kerstin, Paradies, Philippe, Pereira, Thorsten, Persigehl, Mathias, Plauth, Ruben, Plentz, Jürgen, Pohl, Jutta, Riemer, Peter, Reimer, Johanna, Ringwald, Ulrike, Ritterbusch, Elke, Roeb, Barbara, Schellhaas, Peter, Schirmacher, Irene, Schmid, Andreas, Schuler, Von Dietrich, Schweinitz, Daniel, Seehofer, Marianne, Sinn, Alexander, Stein, Andreas, Stengel, Nadine, Steubesand, Christian, Stoll, Andrea, Tannapfel, Anne, Taubert, Jörg, Trojan, Van Ingo, Thiel, Reina, Tholen, Arndt, Vogel, Thomas, Vogl, Hilke, Vorwerk, Frank, Wacker, Oliver, Waidmann, Heiner, Wedemeyer, Henning, Wege, Dane, Wildner, Christian, Wittekind, Marcus-Alexander, Wörns, Peter, Galle, Nisar, Malek, Huu Phuc, Nguyen, Dietrich, von Schweinitz, and Ingo, van Thiel

Subjects
Medizin
Published
2022

50. Unspecific CTL Killing Is Enhanced by High Glucose

Author

Wenjuan, Yang, Andreas, Denger, Caroline, Diener, Frederic, Küppers, Leticia, Soriano-Baguet, Gertrud, Schäfer, Archana K, Yanamandra, Renping, Zhao, Arne, Knörck, Eva C, Schwarz, Martin, Hart, Frank, Lammert, Leticia Prates, Roma, Dirk, Brenner, Grigorios, Christidis, Volkhard, Helms, Eckart, Meese, Markus, Hoth, and Bin, Qu

Subjects
TNF-Related Apoptosis-Inducing Ligand, Phosphatidylinositol 3-Kinases, Receptors, TNF-Related Apoptosis-Inducing Ligand, Glucose, T-Lymphocytes, Cytotoxic
Abstract

TNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both

Published
2021

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