key: cord-0770341-eyx9nmnd authors: Zhou, Yu‐Jie; Zheng, Kenneth I.; Wang, Xiao‐Bo; Sun, Qing‐Feng; Pan, Ke‐Hua; Wang, Ting‐Yao; Ma, Hong‐Lei; Chen, Yong‐Ping; George, Jacob; Zheng, Ming‐Hua title: Metabolic‐associated fatty liver disease is associated with severity of COVID‐19 date: 2020-07-05 journal: Liver Int DOI: 10.1111/liv.14575 sha: bbadf85db9db21eb471f423845cbd9307486eea4 doc_id: 770341 cord_uid: eyx9nmnd The Corona Virus Disease 2019 (COVID‐19) pandemic has attracted increasing worldwide attention. While metabolic‐associated fatty liver disease (MAFLD) affects a quarter of world population, its impact on COVID‐19 severity has not been characterized. We identified 55 MAFLD patients with COVID‐19, who were 1:1 matched by age, sex and obesity status to non‐aged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected patients without MAFLD. Our results demonstrate that in patients aged less than 60 years with COVID‐19, MAFLD is associated with an approximately fourfold increase (adjusted odds ratio 4.07, 95% confidence interval 1.20‐13.79, P = .02) in the probability for severe disease, after adjusting for confounders. Healthcare professionals caring for patients with COVID‐19 need to be aware that there is a positive association between MAFLD and severe illness with COVID‐19. Respiratory disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic. Metabolic-associated fatty liver disease (MAFLD) affects about 20%-30% of people worldwide. 1 However, whether the coexistence of MAFLD affects COVID-19 severity is unknown. We explored the association between MAFLD and COVID-19 severity in non-aged patients with laboratory-proven SARS-CoV-2 infection. The study cohort comprised 55 non-aged patients (<60 years old) with both COVID-19 and MAFLD from three major teaching hospitals (the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Central Hospital and Ruian People's Hospital) in China. The patients were intended to be matched 1:1 by age (±5 years), sex and obesity status (body mass index ± 1 unit) to non-aged SARS-CoV-2-infected patients without MAFLD. Unfortunately, because of limitations in the number of patients with COVID-19, after matching for age and obesity, there were only 37 males in the non-MAFLD cohort and 45 in the MAFLD cohort (P = .08). All subjects were imaged by computed tomography (CT) for the detection of fatty liver. Detailed information on CT attenuation measurement and diagnosis of fatty liver can be referenced in subsection 1 of the Data S1. MAFLD was diagnosed according to the recent consensus criteria. 1,2 Detailed diagnostic criteria for MAFLD are described in subsection 2 of the Data S1. Patients with viral hepatitis were excluded; patients with excess alcohol consumption (>20 g/d in females and 30 g/d in males) were excluded to the extent possible according to the clinical notes. Obesity was defined as body mass index (BMI) ≥ 25 kg/m 2 in Asians, 3 and diabetes mellitus was diagnosed according to the history or haemoglobin A1c ≥ 6.5%. 4 Hypertension and dyslipidaemia were diagnosed according to the literature. 5, 6 Briefly, hypertension was defined as blood pressure ≥ 130/85 mmHg or specific drug treatment. Dyslipidaemia was defined as plasma triglycerides ≥ 1.70 mmol/L, or HDL cholesterol < 1.0 mmol/L for men and <1.3 mmol/L for women, or specific drug treatment. Laboratory parameters were measured on the day of admission. COVID-19 severity was assessed during hospitalization and classified into four clinical subtypes (mild, moderate, severe and critical), based on the Chinese management guideline (see subsection 3 of the Data S1). We defined mild and moderate COVID-19 subtypes as 'non-severe COVID-19', and severe and critical subtypes as 'severe COVID-19'. All patients received standard treatments according to the COVID-19 management guidance (7th edition). 7 All patients denied any history of active cancer, coronary heart disease or chronic obstructive or restrictive pulmonary disease. The study was approved by the ethics committees of the three hospitals. Continuous variables are expressed as mean ± standard deviation or median [interquartile range] and compared using t test or Mann-Whitney U test, as appropriate. Categorical variables were compared using chi-squared test or Fisher exact test for non-ranked variables, and Kruskal-Wallis test for ranked data. Wilcoxon test (paired samples) was utilized to compare values of liver function tests at admission and during hospitalization. The association between MAFLD and severity of COVID-19 was determined by logistic regression. All statistical tests were two-sided and a value of P less than .05 was considered statistically significant. Statistical analyses were performed using SPSS version 22.0 (IBM Corporation). As shown in Table 1 We then explored impacts of SARS-CoV-2 infection on liver function in 101 patients (49 MAFLD, 52 non-MAFLD) with available information. We compared peak values of aminotransferases, total bilirubin and GGT and minimum albumin value during hospitalization with their corresponding values at admission. We found that ALT, AST, AST/ALT ratio, total bilirubin and GGT were significantly elevated during hospitalization, while the albumin value was significantly decreased during hospitalization compared with that at the time of admission (all P < .001; Table S1 ). MAFLD patients comprised 43.7% of non-severe COVID-19 and 73.9% of severe COVID-19 (P = .01). To adjust for confounding variables, we performed multivariable logistic regression analyses ( Our study has some limitations. Due to the infectious nature of COVID-19 and the emergent situation, fatty liver was detected by CT, rather than the 'gold standard' of liver biopsy or magnetic resonance proton density fat fraction (MR-PDFF). However, previous studies report that fatty liver can also be accurately and reliably diagnosed by Note: Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) measured by univariable and multivariable logistic regression analyses. Model I: adjusted for age and sex. Model II: adjusted for age, sex, smoking, obesity, diabetes mellitus and hypertension. 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