Stephan Buch

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About Stephan Buch:

Universitätsklinikum Dresden - Medizinische Klinik I, Bereich Gastroenterologie & Hepatologie

SEEK ID: https://seek.lisym.org/people/157

Location: Germany

ORCID: Not specified

Joined: 24th Jul 2020

Expertise: Genetics

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LiSyM: Liver Systems Medicine

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

Web page: https://www.lisym.org/

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LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

One of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH. LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research/zones-of-the-liver

Start date: 1st Jan 2016

Organisms: Mus musculus, Rattus rattus, Rattus norvegicus, Homo sapiens

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Universitätsklinikum Dresden - Medizinische Klinik I, Bereich Gastroenterologie & Hepatologie

Country: Germany

City: 01307 Dresden

Web page: https://www.uniklinikum-dresden.de/de/das-klinikum/kliniken-polikliniken-institute/mk1/gastroenterologie

Showing 5 out of a possible 11 Publications Advanced Publications list for this Person with search and filtering

Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study

Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

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Objective 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 …tors 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. Design 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). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10 −9 , OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10 −5 , OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10 −44 ). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Authors: 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, Felix Stickel

Date Published: 5th Jan 2023

Publication Type: Journal

DOI: 10.1136/gutjnl-2022-327196

Citation: Gut 72(2):381-391

Created: 14th Sep 2023 at 16:13, Last updated: 8th Mar 2024 at 07:44

The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

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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 …rotein 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.

Authors: 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, Stephan Buch

Date Published: 2022

Publication Type: Journal

DOI: 10.1002/hep4.1886

Citation: Hepatol Commun 6(5):1213-1226

Created: 14th Sep 2023 at 16:25, Last updated: 8th Mar 2024 at 07:44

Non-alcoholic fatty liver disease Stratification by Liver Lipidomics

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

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Non-alcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution …

Authors: Olga Vvedenskaya, Tim Daniel Rose, Oskar Knittelfelder, Alessandra Palladini, Judith Andrea Heidrun Wodke, Kai Schumann, Jacobo Miranda Ackerman, Yuting Wang, Canan Has, Mario Brosch, Veera Raghavan Thangapandi, Stephan Buch, Thomas Züllig, Jürgen Hartler, Harald C. Köfeler, Christoph Röcken, Ünal Coskun, Edda Klipp, Witigo von Schoenfels, Justus Gross, Clemens Schafmayer, Jochen Hampe, Josch Konstantin Pauling, Andrej Shevchenko

Date Published: 1st Aug 2021

Publication Type: Journal

DOI: 10.1016/j.jlr.2021.100104

Citation: Journal of Lipid Research:100104

Created: 14th Aug 2021 at 18:44, Last updated: 8th Mar 2024 at 07:44

rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

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BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, …

Authors: K. Teo, K. W. M. Abeysekera, L. Adams, E. Aigner, Q. M. Anstee, J. M. Banales, R. Banerjee, P. Basu, T. Berg, P. Bhatnagar, S. Buch, A. Canbay, S. Caprio, A. Chatterjee, Y. D. Ida Chen, A. Chowdhury, A. K. Daly, C. Datz, D. de Gracia Hahn, J. K. DiStefano, J. Dong, A. Duret, C. Emdin, M. Fairey, G. S. Gerhard, X. Guo, J. Hampe, M. Hickman, L. Heintz, C. Hudert, H. Hunter, M. Kelly, J. Kozlitina, M. Krawczyk, F. Lammert, C. Langenberg, J. Lavine, L. Li, H. K. Lim, R. Loomba, P. K. Luukkonen, P. E. Melton, T. A. Mori, N. D. Palmer, C. A. Parisinos, S. G. Pillai, F. Qayyum, M. C. Reichert, S. Romeo, J. I. Rotter, Y. R. Im, N. Santoro, C. Schafmayer, E. K. Speliotes, S. Stender, F. Stickel, C. D. Still, P. Strnad, K. D. Taylor, A. Tybjaerg-Hansen, G. R. Umano, M. Utukuri, L. Valenti, L. E. Wagenknecht, N. J. Wareham, R. M. Watanabe, J. Wattacheril, H. Yaghootkar, H. Yki-Jarvinen, K. A. Young, J. P. Mann

Date Published: 31st Aug 2020

Publication Type: Journal

PubMed ID: 32882372

Citation: J Hepatol. 2020 Aug 31. pii: S0168-8278(20)33598-4. doi: 10.1016/j.jhep.2020.08.027.

Created: 29th Sep 2020 at 12:47, Last updated: 8th Mar 2024 at 07:44

Genome-Wide Association Study for Alcohol-Related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1.

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

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BACKGROUND AND AIMS: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom …

Authors: H. Innes, S. Buch, S. Hutchinson, I. N. Guha, J. R. Morling, E. Barnes, W. Irving, E. Forrest, V. Pedergnan, D. Goldberg, E. Aspinall, S. Barclay, P. Hayes, J. Dillon, H. D. Nischalke, P. Lutz, U. Spengler, J. Fischer, T. Berg, M. Brosch, F. Eyer, C. Datz, S. Mueller, T. Peccerella, P. Deltenre, A. Marot, M. Soyka, A. McQuillin, M. Y. Morgan, J. Hampe, F. Stickel

Date Published: 16th Jun 2020

Publication Type: Journal

PubMed ID: 32561361

Citation: Gastroenterology. 2020 Jun 16. pii: S0016-5085(20)34767-3. doi: 10.1053/j.gastro.2020.06.014.

Created: 29th Sep 2020 at 12:49, Last updated: 8th Mar 2024 at 07:44

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