Abstract
Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has emerged as a significant comorbidity in COVID-19 patients. This retrospective case-control study included 224 COVID-19 patients (112 with MAFLD and 112 without MAFLD) for clinical and biochemical evaluation. Data collection followed a consecutive sampling protocol was performed using a random number generator on the list of eligible patients, incorporating all patients who met the inclusion criteria during the study period to ensure a representative and unbiased clinical sample. MAFLD patients demonstrated considerably worse clinical profiles compared to controls, with higher obesity rates (78% vs. 22%), prolonged hospitalization (84% vs. 16%), and more severe COVID-19 presentations (45% vs. 55%). During infection, significant differences were observed in AST, CRP, HSI, and AST/ALT ratio (p<0.05), while post-infection findings revealed significant changes in AST, PLT, PTT, and HIS (p<0.05), reflecting notable hepatic and hematological disruption. Multivariate logistic regression identified several independent risk factors influencing clinical outcomes. Saudi nationality was a significant predictor (adjOR = 0.289; p = 0.027), while hospital admission carried the highest associated risk (adjOR = 8.315; p < 0.001). COVID-19 severity also remained an independent contributing factor (adjOR = 0.291; p = 0.010). Among post-infection laboratory markers, both platelet count (adjOR = 1.003; p = 0.028) and the AST/ALT ratio (adjOR = 2.674; p = 0.018) were confirmed as independent variables influencing overall outcome. The clinical burden within the MAFLD cohort was substantial, with a mortality rate of 31.3% (35/112) and a recovery rate of only 68.8% (77/112), both significantly lower than in the control group. Notably, MAFLD alone was not found to be directly life-threatening; rather, COVID-19 severity remained the primary driver of adverse outcomes. In conclusion, the study confirms MAFLD as an important prognostic factor in COVID-19 patients, highlighting the need of clinical management for this high-risk population during pandemics.
References
Ahmad, A., Ishtiaq, S. M., Khan, J. A., Aslam, R., Ali, S., & Arshad, M. I. (2021). COVID-19 and comorbidities of hepatic diseases in a global perspective. World Journal of Gastroenterology, 27(13), 1296–1310.
https://doi.org/10.3748/wjg.v27.i13.1296
Alkhouri, N., Kohli, A., Loomba, R., & Harrison, S. A. (2020). Maintaining patient safety and data integrity of nonalcoholic steatohepatitis clinical trials during the severe acute respiratory syndrome-coronavirus 2 pandemic. Hepatology, 72(5), 1509–1513.
https://doi.org/10.1002/hep.31522
AlShaalan, R., Aljiffry, M., Al-Busafi, S., Metrakos, P., & Hassanain, M. (2015). Nonalcoholic fatty liver disease: Noninvasive methods of diagnosing hepatic steatosis. Saudi Journal of Gastroenterology, 21(2), 64–70.
https://doi.org/10.4103/1319-3767.153812
Alwafi, H., Naser, A. Y., Qanash, S., Brinji, A. S., Ghazawi, M. A., Alotaibi, B., Alghamdi, A., Alrhmani, A., Fatehaldin, R., Alelyani, A., Basfar, A., AlBarakati, A., Alsharif, G. F., Obaid, E. F., & Shabrawishi, M. (2021). Predictors of length of hospital stay, mortality, and outcomes among hospitalised COVID-19 patients in Saudi Arabia: A cross-sectional study. Journal of Multidisciplinary Healthcare, 14, 839–852.
https://doi.org/10.2147/JMDH.S304788
Alyami, M. H., Naser, A. Y., Orabi, M. A. A., Alwafi, H., & Alyami, H. S. (2020). Epidemiology of COVID-19 in the Kingdom of Saudi Arabia: An ecological study. Frontiers in Public Health, 8, 1–9.
https://doi.org/10.3389/fpubh.2020.00506
An, Y.-W., Song, S., Li, W.-X., Chen, Y.-X., Hu, X.-P., Zhao, J., Li, Z.-W., Jiang, G.-Y., Wang, C., Wang, J.-C., Yuan, B., & Liu, H.-Q. (2021). Liver function recovery of COVID-19 patients after discharge, a follow-up study. International Journal of Medical Sciences, 18(1), 176–186.
https://doi.org/10.7150/ijms.50691
Angulo, P., Keach, J. C., Batts, K. P., & Lindor, K. D. (1999). Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology, 30(6), 1356–1362.
https://doi.org/10.1002/hep.510300604
Bahardoust, M., Heiat, M., Khodabandeh, M., Karbasi, A., Bagheri-Hosseinabadi, Z., Ataee, M. H., Seidalian, N., Babazadeh, A., Agah, S., & Abyazi, M. A. (2021). Predictors for the severe coronavirus disease 2019 (COVID-19) infection in patients with underlying liver disease: A retrospective analytical study in Iran. Scientific Reports, 11(1), 1–6.
https://doi.org/10.1038/s41598-021-82721-3
Cai, H., Yang, L., Lu, Y., Zhang, S., Ye, C., Zhang, X., Yu, G., Gu, J., Lian, J., Hao, S., Hu, J., Zhang, Y., Jin, C., Sheng, J., Yang, Y., & Jia, H. (2021). High body mass index is a significant risk factor for the progression and prognosis of imported COVID-19: A multicenter, retrospective cohort study. BMC Infectious Diseases, 21(1), 147.
https://doi.org/10.1186/s12879-021-05818-0
Calapod, O. P., Marin, A. M., Tribus, L. C., & Fierbinjeanu-Braticevici, C. (2020). Non-alcoholic fatty liver disease in diabetic patients as risk factor for poor prognosis of COVID-19: An update of potential mechanisms and treatment considerations. Farmacia, 68(5), 779–784.
https://doi.org/10.31925/farmacia.2020.5.2
Campos-Murguía, A., Román-Calleja, B. M., Toledo-Coronado, I. V., González-Regueiro, J. A., Solís-Ortega, A. A., Kúsulas-Delint, D., Cruz-Contreras, M., Cruz-Yedra, N., Cubero, F. J., Nevzorova, Y. A., Martínez-Cabrera, C. F., Moreno-Guillén, P., Lozano-Cruz, O. A., Chapa-Ibargüengoitia, M., Gulías-Herrero, A., Aguilar-Salinas, C. A., Ruiz-Margáin, A., & Macías-Rodríguez, R. U. (2021). Liver fibrosis in patients with metabolic associated fatty liver disease is a risk factor for adverse outcomes in COVID-19. Digestive and Liver Disease, 53(5), 525–533.
https://doi.org/10.1016/j.dld.2021.01.019
Chen, F., Chen, W., Chen, J., Xu, D., Xie, W., Wang, X., & Xie, Y. (2021). Clinical features and risk factors of COVID-19-associated liver injury and function: A retrospective analysis of 830 cases. Annals of Hepatology, 21, 100267.
https://doi.org/10.1016/j.aohep.2020.09.011
Cordeiro, A., Ribamar, A., & Ramalho, A. (2022). Adipose tissue dysfunction and MAFLD in obesity on the scene of COVID-19. Clinics and Research in Hepatology and Gastroenterology, 46(3), 101807.
https://doi.org/10.1016/j.clinre.2021.101807
Del Nonno, F., Nardacci, R., Colombo, D., Visco-Comandini, U., Cicalini, S., Antinori, A., Marchioni, L., D'Offizi, G., Piacentini, M., & Falasca, L. (2021). Hepatic failure in COVID-19: Is iron overload the dangerous trigger? Cells, 10(5), 1103.
https://doi.org/10.3390/cells10051103
Ding, Z. Y., Li, G. X., Chen, L., Shu, C., Song, J., Wang, W., Wang, Y. W., Chen, Q., Jin, G. N., Liu, T. T., Liang, J. N., Zhu, P., Zhu, W., Li, Y., Zhang, B. H., Feng, H., Zhang, W. G., Yin, Z. Y., Yu, W. K., Yang, Y., & Tongji Multidisciplinary Team for Treating COVID-19. (2021). Association of liver abnormalities with in-hospital mortality in patients with COVID-19. Journal of Hepatology, 74(6), 1295–1302.
https://doi.org/10.1016/j.jhep.2020.12.012
Dongiovanni, P., Meroni, M., Longo, M., & Fracanzani, A. L. (2020). MAFLD in COVID-19 patients: An insidious enemy. Expert Review of Gastroenterology and Hepatology, 14(10), 867–872.
https://doi.org/10.1080/17474124.2020.1801417
Emsen, A., Sumer, S., Tulek, B., Cizmecioglu, H., Vatansev, H., Goktepe, M. H., Kanat, F., Koksal, Y., Arslan, U., & Artac, H. (2022). Correlation of myeloid-derived suppressor cells with C-reactive protein, ferritin and lactate dehydrogenase levels in patients with severe COVID-19. Scandinavian Journal of Immunology, 95(1), e13108.
https://doi.org/10.1111/sji.13108
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., Grønbæk, H., Cortez-Pinto, H., Fan, J., Valenti, L., Abdelmalek, M., Romero-Gomez, M., Rinella, M., Arrese, M., Bedossa, P., & Younossi, Z. (2020). MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology, 158(7), 1999–2014.
https://doi.org/10.1053/j.gastro.2019.11.312
Farrell, G. C., George, J., Hall, P. D. M., McCullough, A. J., Clouston, A. D., & Powell, E. E. (Eds.). (2005). Fatty liver disease: NASH and related disorders. Blackwell Publishing.
Feng, G., Zheng, K. I., Yan, Q. Q., Rios, R. S., Targher, G., Byrne, C. D., Van Poucke, S., Liu, W. Y., & Zheng, M. H. (2020). COVID-19 and liver dysfunction: Current insights and emergent therapeutic strategies. Journal of Clinical and Translational Hepatology, 8(1), 18–24.
https://doi.org/10.14218/JCTH.2020.00018
Feyissa, G. T., Tolu, L. B., & Ezeh, A. (2021). COVID-19 death reporting inconsistencies and working lessons for low- and middle-income countries: Opinion. Frontiers in Medicine, 8, 595787.
https://doi.org/10.3389/fmed.2021.595787
Hanff, T. C., Chirinos, J. A., Giri, J., & Cohen, J. B. (2020). Thrombosis in COVID-19. August, 1578–1589.
https://doi.org/10.1002/ajh.25982
Hernandez Roman, J., & Siddiqui, M. S. (2020). The role of noninvasive biomarkers in diagnosis and risk stratification in nonalcoholic fatty liver disease. Endocrinology, Diabetes & Metabolism, 3(4), e00127.
https://doi.org/https://doi.org/10.1002/edm2.127
Hartl, L., Haslinger, K., Angerer, M., Jachs, M., Simbrunner, B., Bauer, D. J., & Reiberger, T. (2022). Age-adjusted mortality and predictive value of liver chemistries in a Viennese cohort of COVID-19 patients. Liver International, 42(6), 1297–1307.
https://doi.org/10.1111/liv.15274
Huang, R., Zhu, L., Wang, J., Xue, L., Liu, L., Yan, X., Huang, S., Li, Y., Yan, X., Zhang, B., Xu, T., Li, C., Ji, F., Ming, F., Zhao, Y., Cheng, J., Wang, Y., Zhao, H., Hong, S., Chen, K., & Wu, C. (2020). Clinical features of patients with COVID-19 with nonalcoholic fatty liver disease. Hepatology Communications, 4(12), 1758–1768.
https://doi.org/10.1002/hep4.1592
Hussain, A., Vasas, P., & El-Hasani, S. (2020). Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease. Metabolism: Clinical and Experimental, 108, 154256.
https://doi.org/10.1016/j.metabol.2020.154256
Iba, T., Levy, J. H., Levi, M., & Thachil, J. (2020). Coagulopathy in COVID-19. March, 2103–2109.
https://doi.org/10.1111/jth.14975
Jagirdhar, G. S. K., Pattnaik, H., Banga, A., Qasba, R. K., Rama, K., Reddy, S. T., Bucharles, A. C. F., Kashyap, R., Elmati, P. R., Bansal, V., Bains, Y., DaCosta, T., & Surani, S. (2023). Association of non-alcoholic fatty liver disease and metabolic-associated fatty liver disease with COVID-19-related intensive care unit outcomes: A systematic review and meta-analysis. Medicina, 59(7), 1239.
https://doi.org/10.3390/medicina59071239
Ji, D., Qin, E., Xu, J., Zhang, D., Cheng, G., Wang, Y., & Lau, G. (2020). Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study. Journal of Hepatology, 73(2), 451–453.
https://doi.org/10.1016/j.jhep.2020.03.044
Lee, J., Kim, D., Jung, H., Lee, C., In, J., Kim, W., Jun, Y., Yoon, J., Cho, S., Sung, M., & Lee, H. (2010). Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease. Digestive and Liver Disease, 42(7), 504–509.
https://doi.org/10.1016/j.dld.2009.08.002
Liu, D., Zheng, Y., Kang, J., Wang, D., Bai, L., Mao, Y., Zha, G., Tang, H., & Zhang, R. (2022). Not only high number and specific comorbidities but also age are closely related to progression and poor prognosis in patients with COVID-19. Frontiers in Medicine, 8, 736109.
https://doi.org/10.3389/fmed.2021.736109
Mahamid, M., Nseir, W., Khoury, T., Mahamid, B., Nubania, A., Sub-Laban, K., Schifter, J., Mari, A., Sbeit, W., & Goldin, E. (2021). Nonalcoholic fatty liver disease is associated with COVID-19 severity independently of metabolic syndrome: A retrospective case-control study. European Journal of Gastroenterology and Hepatology, 33(12), 1578–1581.
https://doi.org/10.1097/MEG.0000000000001902
Malik, P., Patel, U., Patel, K., Martin, M., Shah, C., Mehta, D., Malik, F. A., & Sharma, A. (2021). Obesity a predictor of outcomes of COVID-19 hospitalized patients: A systematic review and meta-analysis. Journal of Medical Virology, 93(2), 1188–1193.
https://doi.org/10.1002/JMV.26555
Marcotullio, P. J., & Schmeltz, M. (2021). COVID-19 in three global cities: Comparing impacts and outcomes. Journal of Extreme Events, 8(2).
https://doi.org/10.1142/s2345737621500135
Marjot, T., Webb, G. J., Barritt, A. S., Moon, A. M., Stamataki, Z., Wong, V. W., & Barnes, E. (2021). COVID-19 and liver disease: Mechanistic and clinical perspectives. Nature Reviews Gastroenterology and Hepatology, 18(5), 348–364.
https://doi.org/10.1038/s41575-021-00426-4
Miele, L., Napodano, C., Cesario, A., De Magistris, A., Pocino, K., Basile, U., Rapaccini, G. L., Gasbarrini, A., & Grieco, A. (2021). COVID-19, adaptive immune response and metabolic-associated liver disease. Liver International, 41, 2560–2577.
https://doi.org/10.1111/liv.15061
Ministry of Health Saudi Arabia. (2020). Coronavirus Disease 19 Guidelines. pp.1–33.
https://www.moh.gov.sa/en/ministry/mediacenter/publications/pages/covid19.aspx
Okhowat, A. (2022). A Framework for COVID-19 response. In Public Health Intervention for the COVID-19 Pandemic from Virus to Vaccine (pp. 3–16). World Scientific Publishing Co. Pte. Ltd.
https://EconPapers.repec.org/RePEc:wsi:wschap:9789811249723_0001
Parks, E. J., Skokan, L. E., Timlin, M. T., & Dingfelder, C. S. (2005). Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. Journal of Clinical Investigation, 115(5), 1343–1351.
https://doi.org/10.1172/JCI23621
Priego-Parra, B. A., Triana-Romero, A., Martínez-Pérez, G. P., Reyes-Diaz, S. A., Ordaz-Alvarez, H. R., Bernal-Reyes, R., Icaza-Chávez, M. E., Martínez-Vázquez, S. E., Cano-Contreras, A. D., Vivanco-Cid, H., & Remes-Troche, J. M. (2024). Hepatic steatosis index (HSI): A valuable biomarker in subjects with metabolic dysfunction-associated fatty liver disease (MAFLD). Annals of Hepatology, 29, 101391.
https://doi.org/10.1016/j.aohep.2024.101391
Radonjić, T., Milićević, O., Jovanović, I., Zdravković, M., Dukić, M., Mandić, O. M., Bjekić-Macut, J., Marković, O. B., Todorović, Z., Brajković, M., Nikolić, N., Klašnja, S., Popadić, V., Divac, A., Marinković, M., Alhayek, N., & Branković, M. S. (2022). Elevated transaminases as predictors of COVID-19 pneumonia severity. Medicina, 58(7), 842.
https://doi.org/10.3390/medicina58070842
Salazar, M. R. (2021). Is hypertension without any other comorbidities an independent predictor for COVID-19 severity and mortality? Journal of Clinical Hypertension, 23(2), 232–234.
https://doi.org/10.1111/jch.14144
Sarkar, M., Madabhavi, I. V., Quy, P. N., & Govindagoudar, M. B. (2021). COVID-19 and coagulopathy. Clinical Respiratory Journal, 15(12), 1259–1274.
https://doi.org/10.1111/CRJ.13438
Sharma, A., Jaiswal, P., Kerakhan, Y., Saravanan, L., Murtaza, Z., Zergham, A., Honganur, N. S., Akbar, A., Deol, A., Francis, B., Patel, S., Mehta, D., Jaiswal, R., Singh, J., Patel, U., & Malik, P. (2021). Liver disease and outcomes among COVID-19 hospitalized patients: A systematic review and meta-analysis. Annals of Hepatology, 21, 100273.
https://doi.org/10.1016/j.aohep.2020.10.001
Singh, A., Hussain, S., & Antony, B. (2021). Non-alcoholic fatty liver disease and clinical outcomes in patients with COVID-19: A comprehensive systematic review and meta-analysis. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 15(3), 813–822.
https://doi.org/10.1016/j.dsx.2021.03.019
Slusher, A. L., Hu, P., Samuels, S., Tokoglu, F., Lat, J., Li, Z., Alguard, M., Strober, J., Vatner, D., Shabanova, V., & Caprio, S. (2023). Rising NAFLD and metabolic severity during the SARS-CoV-2 pandemic among children with obesity in the United States. Obesity, 31(5), 1383–1391.
https://doi.org/10.1002/oby.23728
Tchang, B. G., Askin, G., Sahagun, A., Hwang, J., Huang, H., Mendelsohn Curanaj, F. A., Seley, J. J., Safford, M. M., Alonso, L. C., Aronne, L. J., & Shukla, A. P. (2021). The independent risk of obesity and diabetes and their interaction in COVID-19: A retrospective cohort study. Obesity, 29(6), 971–975.
https://doi.org/10.1002/oby.23172
Vancsa, S., Hegyi, P. J., Zadori, N., Szako, L., Vörhendi, N., Ocskay, K., & Par, G. (2020). Pre-existing liver diseases and on-admission liver-related laboratory tests in COVID-19: A prognostic accuracy meta-analysis with systematic review. Frontiers in Medicine, 7, 572115.
https://doi.org/10.3389/fmed.2020.572115
Vázquez-Medina, M. U., Cerda-Reyes, E., Galeana-Pavón, A., López-Luna, C. E., Ramírez-Portillo, P. M., Ibañez-Cervantes, G., Torres-Vázquez, J., & Vargas-De-León, C. (2022). Interaction of metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease with advanced fibrosis in the death and intubation of patients hospitalized with coronavirus disease 2019. Hepatology Communications, 6(8), 2000–2010.
https://doi.org/10.1002/hep4.1957
Vinken, M. (2021). COVID-19 and the liver: an adverse outcome pathway perspective. Toxicology, 455, 152765.
https://doi.org/10.1016/j.tox.2021.152765
Vrsaljko, N., Samadan, L., Viskovic, K., Mehmedovic, A., Budimir, J., Vince, A., & Papic, N. (2022). Association of nonalcoholic fatty liver disease with COVID-19 severity and pulmonary thrombosis: CovidFAT, a prospective, observational cohort study. Open Forum Infectious Diseases, 9(4).
https://doi.org/10.1093/ofid/ofac073
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., Zhao, Y., Li, Y., Wang, X., & Peng, Z. (2020). Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 323(11), 1061–1069.
https://doi.org/10.1001/jama.2020.1585
Webb, G. J., Marjot, T., Cook, J. A., Aloman, C., Armstrong, M. J., Brenner, E. J., Catana, M. A., Cargill, T., Dhanasekaran, R., García-Juárez, I., Hagström, H., Kennedy, J. M., Marshall, A., Masson, S., Mercer, C. J., Perumalswami, P. V., Ruiz, I., Thaker, S., Ufere, N. N., Barnes, E., & Moon, A. M. (2020). Outcomes following SARS-CoV-2 infection in liver transplant recipients: An international registry study. Lancet Gastroenterology and Hepatology, 5(11), 1008–1016.
https://doi.org/10.1016/S2468-1253(20)30271-5
Xu, X., Yang, T., An, J., Li, B., & Dou, Z. (2025). Liver injury in sepsis: Manifestations, mechanisms and emerging therapeutic strategies. Frontiers in Immunology, 16, 1575554.
https://doi.org/10.3389/fimmu.2025.1575554
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease: Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73–84.
https://doi.org/10.1002/hep.28431
Zaidi, S. R. H., & Rout, P. (2025). Interpretation of Blood Clotting Studies and Values (PT, PTT, aPTT, INR, Anti-Factor Xa, D-Dimer). In StatPearls. StatPearls Publishing.
https://www.ncbi.nlm.nih.gov/books/NBK604215/
Zarifian, A., Zamiri, M., Soheil, B., & Mahdi, A. (2020). Gastrointestinal and hepatic abnormalities in patients with confirmed COVID-19: A systematic review and meta-analysis. Journal of Medical Virology.
https://doi.org/10.1002/jmv.26314
Zhang, C., Shi, L., & Wang, F. S. (2020). Liver injury in COVID-19: Management and challenges. Lancet Gastroenterology and Hepatology, 5(5), 428–430.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 Mesk Saleh Ali Ghulais, Hasni Idayu Saidi, Huzwah Khaza'ai, Khaled Belal, Ummi Nadira Daut, AbdulRahman Muthanna, Nurliyana Najwa Md Razip