Jiuling Li1, Aowen Tian1, Haoxue Zhu2, Lanlan Chen3, Jianping Wen4, Wanqing Liu5, Peng Chen6. 1. Department of Pathology, College of Basic Medical Sciences, Jilin University, Changchun, China. 2. Teaching Department, First Affiliated Hospital of Jilin University, Changchun, China. 3. School of Clinical Medicine, Jilin University, Changchun, China. 4. Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, China. 5. Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan. Electronic address: wliu@wayne.edu. 6. Department of Pathology, College of Basic Medical Sciences, Jilin University, Changchun, China; Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, China. Electronic address: pchen@jlu.edu.cn.
Abstract
BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has witnessed more than 4.5 million deaths as of the time of writing. Whether nonalcoholic fatty liver disease (NAFLD) increases the risk for severe COVID-19 remains unclear. We sought to address this question using 2-sample Mendelian randomization (TSMR) analysis approaches in large cohorts. METHODS: We performed large-scale TSMR analyses to examine whether there is a causal relationship between NAFLD, serum alanine aminotransferase, grade of steatosis, NAFLD Activity Score, or fibrosis stage and severe COVID-19. To maximize the power of this analysis, we performed a genome-wide meta-analysis to identify single nucleotide polymorphisms associated with NAFLD. We also examined the impact of 20 major comorbid factors of NAFLD on severe COVID-19. RESULTS: Univariate analysis of the UK Biobank data demonstrated a significant association between NAFLD and severe COVID-19 (odds ratio [OR], 3.06; P = 1.07 × 10-6). However, this association disappeared after demographic and comorbid factors were adjusted (OR, 1.57; P = .09). TSMR study indicated that NAFLD (OR, 0.97; P = .61), alanine aminotransferase level (OR, 1.03; P = .47), grade of steatosis (OR, 1.08; P = .41), NAFLD Activity Score (OR, 1.02; P = .39), and fibrosis stage (OR, 1.01; P = .87) were not associated with severe COVID-19. Among all NAFLD-related comorbid factors, body mass index (OR, 1.73; P = 7.65 × 10-9), waist circumference (OR, 1.76; P = 2.58 × 10-5), and hip circumference (OR, 1.33; P = 7.26 × 10-3) were the only ones demonstrated a causal impact on severe COVID-19. CONCLUSIONS: There is no evidence supporting that NAFLD is a causal risk factor for severe COVID-19. Previous observational associations between NAFLD and COVID-19 are likely attributed to the correlation between NAFLD and obesity.
BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has witnessed more than 4.5 million deaths as of the time of writing. Whether nonalcoholic fatty liver disease (NAFLD) increases the risk for severe COVID-19 remains unclear. We sought to address this question using 2-sample Mendelian randomization (TSMR) analysis approaches in large cohorts. METHODS: We performed large-scale TSMR analyses to examine whether there is a causal relationship between NAFLD, serum alanine aminotransferase, grade of steatosis, NAFLD Activity Score, or fibrosis stage and severe COVID-19. To maximize the power of this analysis, we performed a genome-wide meta-analysis to identify single nucleotide polymorphisms associated with NAFLD. We also examined the impact of 20 major comorbid factors of NAFLD on severe COVID-19. RESULTS: Univariate analysis of the UK Biobank data demonstrated a significant association between NAFLD and severe COVID-19 (odds ratio [OR], 3.06; P = 1.07 × 10-6). However, this association disappeared after demographic and comorbid factors were adjusted (OR, 1.57; P = .09). TSMR study indicated that NAFLD (OR, 0.97; P = .61), alanine aminotransferase level (OR, 1.03; P = .47), grade of steatosis (OR, 1.08; P = .41), NAFLD Activity Score (OR, 1.02; P = .39), and fibrosis stage (OR, 1.01; P = .87) were not associated with severe COVID-19. Among all NAFLD-related comorbid factors, body mass index (OR, 1.73; P = 7.65 × 10-9), waist circumference (OR, 1.76; P = 2.58 × 10-5), and hip circumference (OR, 1.33; P = 7.26 × 10-3) were the only ones demonstrated a causal impact on severe COVID-19. CONCLUSIONS: There is no evidence supporting that NAFLD is a causal risk factor for severe COVID-19. Previous observational associations between NAFLD and COVID-19 are likely attributed to the correlation between NAFLD and obesity.
Authors: Elizabeth J Williamson; Alex J Walker; Krishnan Bhaskaran; Seb Bacon; Chris Bates; Caroline E Morton; Helen J Curtis; Amir Mehrkar; David Evans; Peter Inglesby; Jonathan Cockburn; Helen I McDonald; Brian MacKenna; Laurie Tomlinson; Ian J Douglas; Christopher T Rentsch; Rohini Mathur; Angel Y S Wong; Richard Grieve; David Harrison; Harriet Forbes; Anna Schultze; Richard Croker; John Parry; Frank Hester; Sam Harper; Rafael Perera; Stephen J W Evans; Liam Smeeth; Ben Goldacre Journal: Nature Date: 2020-07-08 Impact factor: 49.962
Authors: Thomas Marjot; Christiane S Eberhardt; Tobias Boettler; Luca S Belli; Marina Berenguer; Maria Buti; Rajiv Jalan; Mario U Mondelli; Richard Moreau; Daniel Shouval; Thomas Berg; Markus Cornberg Journal: J Hepatol Date: 2022-07-20 Impact factor: 30.083