Metabolic dysfunction-associated fatty liver disease ups risk of severe COVID-19

Metabolic dysfunction-associated fatty liver disease (MAFLD) can escalate the incidence of severe COVID-19, but no association between MAFLD and COVID-19 death has been confirmed, suggest the results of a meta-analysis.

“Since only four studies analysing the correlation between MAFLD and COVID-19 death were included, and all of which were from non-Chinese countries, this conclusion may be drawn by the synthesis of several factors, such as ethnic and regional diversity, the discrepancy of liver function status when infected with SARS-CoV-2, and differences in severity of COVID-19,” the researchers said.

The databases of PubMed, Embase, Cochrane Library, and Web of Science were accessed for eligible studies before 11 March 2021. The quality of these studies was assessed using the Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality scale.

The researchers conducted a pooled analysis using the software RevMan version 5.3 and Stata version 15.0 SE, as well as a sensitivity analysis to examine the stability of their results. In addition, they assessed publication bias via funnel plots, Egger test, and trim-and-fill analysis.

Seven studies, including a total of 2,141 patients with COVID-19, met the eligibility criteria. The meta-analysis confirmed that MAFLD heightened the risk of severe COVID-19 (odds ratio, 1.80, 95 percent confidence interval [CI], 1.53–2.13; p<0.0001). [J Clin Gastroenterol 2021;55:830-835]

However, the presence of MAFLD was not associated with the occurrence of death due to COVID-19. The pooled prevalence of MAFLD among COVID-19 patients was 36 percent (95 percent CI, 0.23–0.49; p<0.0001). The stability of the initial results was confirmed in sensitivity analysis.

“We found that MAFLD increases the risk of severe COVID-19; it is consistent with previous studies,” the researchers said. “However, the mechanism of this remains unclear.” [Metabolism 2020;108:154244; Liver Int 2020;40:2160-2163]

A study by Sharma and Kumar explained that an excess of free fatty acids in MAFLD patients enter the liver and then initiate Kupffer cells. The polarization status of these cells changes from anti-inflammatory M2 to proinflammatory M1 due to the disordered hepatic innate immunity in MAFLD patients. This then boosts the production of tumour necrosis factor-α, interleukin-6, and other cytokines. [Diabetes Metab Syndr 2020;14:825-827]

“Studies have demonstrated the involvement of interleukin-6 in cytokine ‘storm,’ and this ‘storm’ might be the main reason for the deterioration of COVID-19 disease. Thus, we hypothesize that this could be the mechanism by which MAFLD aggravates COVID-19,” the researchers said. [J Med Virol 2020;92:424-432]

“Further investigation is needed to explore the possible mechanism of this association,” the researchers said. “Since MAFLD is common among patients infected with SARS-CoV-2, more care should be given to COVID-19 patients with underlying MAFLD.”

The current study was limited by the small number of included studies, especially those from China, the cross-sectional design of these studies, and the non-identification of the source of heterogeneity of the pooled prevalence.