Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence

Table 1 Summary of various studies describing the association between nonalcoholic fatty liver disease and coronavirus disease 2019

Ref.	Type of study	Study origin	Number of COVID patients/number of NAFLD/NASH patients	Overall impact of occurrence of concomitant NAFLD and COVID-19	Impact of NAFLD on COVID-19 liver injury
Marjot et al[12]	Retrospective	Multinational Cohort	No. of COVID patients with CLD: 745; No. of NAFLD patients: 322	Baseline liver disease stage and ALD are independent risk factor for death from COVID-19	NA
Sarin et al[13]	Retrospective	Multinational Cohort	No. of COVID patients with CLD: 228; No. of fatty liver disease patients: 113	CLD patients with diabetes and obesity are more vulnerable and should be closely monitored	Comorbidities like MAFLD, obesity and diabetes were present in 80% of the patients. MAFLD was the commonest cause for CLD without cirrhosis. Obese cirrhotics had more acute liver injury than normal weight patients [OR 8.9 (95%CI: 1.9-38.8) P = 0.02]. Patients of CLD with diabetes had higher risk [57.7% vs 39.7%, P = 0.01, OR = 2.061.14-3.73)] of liver injury
Ji et al[15]	Retrospective	China	No. of COVID patients: 202; No. of NAFLD patients: 76	Patients with NAFLD also had a higher risk of progression to severe COVID-19 and longer viral shedding time	Patients with NAFLD had a higher likelihood of abnormal liver function from admission to discharge [70% (53/76) vs 11.1% (14/126); P < 0.0001] compared to patients without NAFLD
Zhou et al[16]	Retrospective	Wenzhou, China	No. of COVID patients: 327; No. of patients with fatty liver disease: 93	In patients younger than 60 yr, a more than 2-fold higher prevalence of severe COVID-19 was observed in those with MAFLD compared to those without. MAFLD was not associated with disease severity in multivariable analysis in elderly patients	NA
Mushtaq et al[17]	Retrospective	Qatar	No. of COVID patients: 589; No. of NAFLD patients: 320	NAFLD was not an independent predictor of mortality, disease severity on presentation, or disease progression in patients with COVID-19	Presence of NAFLD was a predictor of the development of mild liver injury (OR 2.99; 95%CI: 1.62-4.37; P = 0.000) and moderate liver injury (OR 5.104; 95%CI: 3.21-6.99; P = 0.000)
Huang et al[18]	Retrospective	Jiangsu, China	No. of COVID patients: 280; No. of NAFLD patients: 86	No patient developed severe liver-related complications during hospitalization	Concurrent NAFLD was identified as a risk factor of elevated ALT (OR, 2.962; 95%CI: 1.745-5.028; P < 0.001) on univariate analysis. Concurrent NAFLD (OR, 2.956; 95%CI: 1.526-5.726; P = 0.001) was an independent risk factor of ALT elevation on multivariate analysis
Fondevila et al[24]	Retrospective	Spain	No. of patients without NAFLD: 17; No. of patients with NAFLD: 77	Obese patients with NASH show markedly higher expression of ACE2 and TMPRSS2, suggesting that advanced stages of NAFLD might predispose individuals to COVID-19	NA
Biquard et al[25]	Retrospective	France	No. of patients without fatty liver disease: 28; No. of patients with fatty liver disease: 26	MAFLD is not associated with changes in liver expression of genes implicated in SARS-CoV-2 infection	NA
Zheng et al[28]	Retrospective	Wenzhou, China	No. of COVID patients: 214; No. of NAFLD patients: 66	Risk of obesity to COVID-19 severity is greater in those with compared to those without MAFLD	NA
Ghoneim et al[29]	Retrospective	Multination electronic health records	No. of COVID patients: 8885; No. of NAFLD patients: 102	The adjusted odds ratio of having COVID-19 were higher in patients if they were diagnosed with NASH	NA
Targher et al[33]	Retrospective	Zhejiang Province, China	No. of COVID patients: 310; No. of NAFLD patients: 94	Patients with MAFLD with increased FIB-4 or NFS are at higher likelihood of having severe COVID-19 illness, irrespective of metabolic comorbidities	COVID-19 patients with MAFLD with intermediate or high FIB-4 scores were more likely to have higher liver enzymes [AST > 40 IU/L (%) -27.8/57.1, ALT > 40 IU/L (%) -30.6/42.9], compared with their counterparts with low FIB-4 score or those without MAFLD [AST > 40 IU/L (%) 7.9/9.1, ALT > 40 IU/L (%) -13/29.6], P < 0.001
Forlano et al[34]	Retrospective	Imperial College Healthcare NHS Trust (London, United Kingdom)	No. of COVID patients: 193; No. of NAFLD patients: 61	Presence of NAFLD per se was not associated with worse outcomes in hospitalised patients. Mortality was associated with pronounced inflammatory response in NAFLD group	NA
Gao et al[35]	Retrospective	3 Chinese hospitals: (the First Affiliated Hospital of Wenzhou Medical University, the Ningbo No. 2 Hospital, and the Ruian People’s Hospital)	No. of COVID-19 patients: 167; No. of MAFLD patients: 46	MAFLD patients with elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19	NA
Sachdeva et al[37]	Pooled analysis	-	No. of COVID patients: 8142; No. of NAFLD patients: 833	NAFLD is a predictor of severe COVID-19, even after adjusting for the presence of obesity	NA

NAFLD: Nonalcoholic fatty liver disease; COVID-19: Coronavirus disease 2019; CLD: Chronic liver disease; ALD: Alcohol-associated liver disease; NA: Not available; MAFLD: Metabolic associated fatty liver disease; CI: Confidence interval; OR: Odds ratio; ALT: Alanine aminotransferase; NASH: Nonalcoholic steatohepatitis; ACE2: Angiotensin-converting enzyme 2; TMPRSS2: Transmembrane serine protease 2; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; AST: Aspartate aminotransferase; IL-6: Interleukin-6.