LIVER COMORBIDITIES AND COVID19 Metabolic Dysfunction Associated Fatty

LIVER CO-MORBIDITIES AND COVID-19 Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD) and COVID- 19 Menso Westerouen van Meeteren and Joost PH Drenth Radboud UMC, Nijmegen, The Netherlands

Content MAFLD and risk of SARS-Co. V-2 transmission MAFLD and COVID-19 prognosis.

Risk of acquiring SARS-Co. V-2 infection Unknown if MAFLD increases risk of acquiring SARS-Co. V-2 infection. ACE-2 receptor speculated as potential cause for increased transmission. ACE-II expression low in healthy liver Chronic Liver liver injury increases ACE-2 expression in: fibrosis mice models Human hepatitis C Cirrhosis explants (Paizis, Tikellis et al. 2005)

ACE-2 role in MAFLD Ang 1 -7 activator reduces steatosis and inflammatory markers in mice ACE-2 activator decreases lipogenesis ACE-2 knock-out mice develop Insulin resistance Spontaneous liver fibrosis Feltenberger, Andrade et al. 2013 de Macedo, Guimarares et al. 2015) Osterreicher, Taura et al. 2009

RAS modulation in MAFLD & Liver injury RAS modulation potential therapeutic drug target in MAFLD and liver fibrosis (Ahmadian, Pennefather et al. 2016)

MAFLD & COVID-19 Prognosis

Metabolic risk factors & severe COVID-19 course Systematic review and meta-analysis, 20 articles (4062 COVID-19 patients) Diabetes, hypertension and CVD increased likelihood of severe disease (Xu, Mao et al. 2020)

MAFLD & COVID-19 severity Cohort study of 202 COVID-19 patients (MAFLD, n=76) Patients with MAFLD had: Higher risk of respiratory disease progression (44. 7 vs. 6. 6%) Higher likelihood of abnormal liver biochemistry (70% vs. 11. 1%) (Xu, Mao et al. 2020)

MAFLD & COVID-19 severity Cohort study of N= 202 COVID-19 patients (MAFLD, n=76) Patients with MAFLD had: higher risk of respiratory disease progression (44. 7 vs. 6. 6%) higher likelihood of abnormal liver biochemistry (70% vs. 11. 1%) (Xu, Mao et al. 2020)

Obesity in MAFLD patients & COVID-19 severity Chinese cohort study selected N=66 MAFLD patients Obesity (BMI > 25 kg/m 2) (n=45) Increased the risk of severe COVID-19 Significant after adjustment for other risk factors (Zheng, Gao et al. 2020)

MAFLD and community acquired pneumonia (CAP) Nested case control study N=561 hospitalized CAP patients 30 -day 17% mortality from pneumonia: 5. 8% in MAFLD patients in non-MAFLD patients (Nseir, Mograbi et al. 2019)

Conclusions Unknown if MAFLD increases risk of SARS-Co. V-2 transmission MAFLD and associated metabolic risk factors increase likelihood of severe course of COVID-19 disease.