NAFLD does not raise severe COVID-19 risk

There is no causal relationship between genetic predisposition to nonalcoholic fatty liver disease (NAFLD) and increased risk of developing severe COVID-19, according to a Mendelian randomization study.

To determine whether NAFLD, serum alanine aminotransferase (ALT), grade of steatosis, NAFLD Activity Score (NAS), or fibrosis stage was a causal risk factor for severe COVID-19, researchers conducted a genome-wide meta-analysis (GWMA) to identify single-nucleotide polymorphisms (SNPs) associated with NAFLD. They also looked at the impact of 20 major comorbid factors of NAFLD on severe COVID-19.

The study population comprised 8,267 individuals of 177 European ancestry who tested positive for SARS-CoV-2. Of these, 556 developed severe COVID-19.

Univariate regression analysis revealed a significant association between NAFLD and severe COVID-19 (odds ratio [OR], 3.06; p=1.07×10⁻⁶). However, this association disappeared following adjustments for demographic and comorbid factors (OR, 1.61; p=0.08).

Furthermore, two-sample Mendelian randomization (TSMR) analysis showed that severe COVID-19 was not associated with NAFLD (OR, 0.97; p=0.61), ALT level (OR, 1.03; p=0.47), grade of steatosis (OR, 1.08; p=0.41), NAS (OR, 1.02; p=0.39), and fibrosis stage (OR, 1.01; p=0.87).

Only three NAFLD-related comorbid factors exerted a causal impact on severe COVID-19. These were 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).

In light of the findings, previous observational associations between NAFLD and COVID-19 are likely attributed to the correlation between NAFLD and obesity. Taken together, weight control may be the most critical modifiable risk factor for preventing the development of severe COVID-19 among NAFLD patients.