Sonja Lang1,2, Anna Martin1, Xinlian Zhang3, Fedja Farowski4,5,6, Hilmar Wisplinghoff7,8,9, Maria J G T Vehreschild4,5,6, Marcin Krawczyk10,11, Angela Nowag7,9, Anne Kretzschmar7, Claus Scholz7, Philipp Kasper1, Christoph Roderburg12, Raphael Mohr13, Frank Lammert10,14, Frank Tacke13, Bernd Schnabl2,15, Tobias Goeser1, Hans-Michael Steffen1, Münevver Demir13. 1. Faculty of Medicine, Department of Gastroenterology and Hepatology, University Hospital Cologne, University of Cologne, Cologne, Germany. 2. Department of Medicine, University of California San Diego, La Jolla, CA, USA. 3. Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA. 4. Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany. 5. German Centre for Infection Research (DZIF), Partner Site Bonn/Cologne, Cologne, Germany. 6. Department of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, Frankfurt, Germany. 7. Wisplinghoff Laboratories, Cologne, Germany. 8. Institute for Virology and Medical Microbiology, University Witten/Herdecke, Witten, Germany. 9. Faculty of Medicine, Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, University of Cologne, Cologne, Germany. 10. Department of Medicine II, Saarland University Medical Center, Homburg, Germany. 11. Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. 12. Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 13. Department of Hepatology and Gastroenterology, Charité University Medicine, Campus Virchow Clinic and Campus Charité Mitte, Berlin, Germany. 14. Hannover Medical School (MHH), Hannover, Germany. 15. Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
Abstract
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown. METHODS: In this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed. RESULTS: Complete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m2 : 1.23, 95% CI 1.10-1.37, P < .001). The PNPLA3 risk allele had the strongest association with the histological grade of steatosis (OR 5.32, 95% CI 1.56-18.11, P = .007), followed by specific dietary patterns. Low abundances of Faecalibacterium, Bacteroides and Prevotella and high abundances of Gemmiger were associated with the degree of inflammation, ballooning and stages of fibrosis, even after taking other cofactors into account. CONCLUSIONS: BMI had the strongest association with histological fibrosis, but PNPLA3 gene variants, gut bacterial features and dietary factors were all associated with different histology features, which underscore the multifactorial pathogenesis of NAFLD.
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown. METHODS: In this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed. RESULTS: Complete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m2 : 1.23, 95% CI 1.10-1.37, P < .001). The PNPLA3 risk allele had the strongest association with the histological grade of steatosis (OR 5.32, 95% CI 1.56-18.11, P = .007), followed by specific dietary patterns. Low abundances of Faecalibacterium, Bacteroides and Prevotella and high abundances of Gemmiger were associated with the degree of inflammation, ballooning and stages of fibrosis, even after taking other cofactors into account. CONCLUSIONS: BMI had the strongest association with histological fibrosis, but PNPLA3 gene variants, gut bacterial features and dietary factors were all associated with different histology features, which underscore the multifactorial pathogenesis of NAFLD.
Authors: Paul Angulo; David E Kleiner; Sanne Dam-Larsen; Leon A Adams; Einar S Bjornsson; Phunchai Charatcharoenwitthaya; Peter R Mills; Jill C Keach; Heather D Lafferty; Alisha Stahler; Svanhildur Haflidadottir; Flemming Bendtsen Journal: Gastroenterology Date: 2015-04-29 Impact factor: 22.682
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: Sonja Lang; Anna Martin; Fedja Farowski; Hilmar Wisplinghoff; Maria J G T Vehreschild; Jinyuan Liu; Marcin Krawczyk; Angela Nowag; Anne Kretzschmar; Jens Herweg; Bernd Schnabl; Xin M Tu; Frank Lammert; Tobias Goeser; Frank Tacke; Kathrin Heinzer; Philipp Kasper; Hans-Michael Steffen; Münevver Demir Journal: Hepatol Commun Date: 2020-03-26