Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2023; 29(21): 3362-3378
Published online Jun 7, 2023. doi: 10.3748/wjg.v29.i21.3362
Association of non-alcoholic fatty liver and metabolic-associated fatty liver with COVID-19 outcomes: A systematic review and meta-analysis
Gowthami Sai Kogilathota Jagirdhar, Rakhtan K Qasba, Harsha Pattnaik, Kaanthi Rama, Akshat Banga, Shiva Teja Reddy, Anna Carolina Flumignan Bucharles, Rahul Kashyap, Praveen Reddy Elmati, Vikas Bansal, Yatinder Bains, Theodore DaCosta, Salim Surani
Gowthami Sai Kogilathota Jagirdhar, Department of Medicine, Saint Michaels Medical Center, Newark, NJ 07102, United States
Rakhtan K Qasba, Department of Medicine, Green Life Medical College and Hospital, Dhaka 1205, Bangladesh
Harsha Pattnaik, Department of Medicine, Lady Hardinge Medical College, New Delhi 110001, India
Kaanthi Rama, Shiva Teja Reddy, Department of Medicine, Gandhi Medical College, Telangana 500003, India
Akshat Banga, Department of Medicine, Sawai Man Singh Medical College, Jaipur 302004, Rajistan, India
Anna Carolina Flumignan Bucharles, Department of Medicine, Universidade Positivo, Curitiba 81290-000, PR, Brazil
Rahul Kashyap, Research, WellSpan Health, York, PA 17403, United States
Praveen Reddy Elmati, Department of Interventional Pain Medicine, University of Louisville, Louisville, KY 40292, United States
Vikas Bansal, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, United States
Yatinder Bains, Theodore DaCosta, Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, United States
Salim Surani, Department of Medicine, Texas A&M University, College Station, TX 77843, United States
Author contributions: Jagirdhar GSK conceived and designed the study; Jagirdhar GSK, Qasba RK, Rama K, Banga A, Reddy ST, and Flumignan Bucharles AC included studies and data extraction; Jagirdhar GSK, Qasba RK, Pattnaik H, Rama K, Banga A, Elmati PR, and Bansal V contributed to the data processing; Jagirdhar GSK, Qasba RK, Pattnaik H, Rama K, Banga A, Reddy ST, Flumignan Bucharles AC, Kashyap R, Elmati PR, Bansal V, Bains Y, and DaCosta T wrote the original manuscript; Jagirdhar GSK, Kashyap R, Bains Y, DaCosta T, and Surani S revised the paper and approved the final version.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Salim Surani, FCCP, MD, MHSc, Professor, Department of Medicine, Texas A&M University, Administration Building, 400 Bizzell St, College Station, TX 77843, United States.
Received: December 29, 2022
Peer-review started: December 29, 2022
First decision: February 15, 2023
Revised: February 25, 2023
Accepted: April 28, 2023
Article in press: April 28, 2023
Published online: June 7, 2023
Research background

Non-alcoholic fatty liver disease (NAFLD) and its hepatic manifestation metabolic-associated fatty liver disease (MAFLD) have a rising prevalence worldwide. It is a co-morbidity like obesity, hypertension, and chronic kidney disease. NAFLD/MAFLD like obesity is considered chronic inflammatory states according to recent literature. Therefore, patients with NAFLD/MAFLD are hypothesized to have worse outcomes with coronavirus disease 2019 (COVID-19).

Research motivation

Existing literature shows conflicting information on the association of NAFLD/MAFLD in COVID-19 patients. Some studies show worse outcomes with NAFLD/MAFLD and COVID-19 infection. Some studies state it is not a risk factor for severe COVID-19. Understanding the pathophysiology and pathogenesis between fatty liver disease and COVID-19 is necessary for prevention, and management of NAFLD/MAFLD patients. Insight into this relationship will help further research and better preventative and nutritional management of these patients. It is imperative to explore the relationship of NAFLD/MAFLD with COVID-19 to improve patient care and treatment protocols for better outcomes.

Research objectives

In this meta-analysis, we investigated the association between NAFLD/MAFLD with the mortality and severity of COVID-19 infection.

Research methods

A systematic review of literature across five databases was done from January 2019 to June 2022. Observational studies were included. Studies that evaluated NAFLD/MAFLD using lab assessment/biomarker assessment, non-invasive imaging, or liver biopsy were included. We registered our study protocol in Prospero and followed the “PRISMA” guidelines (Figure 1). Meta-analysis was conducted on studies with outcomes for hospitalization, hospital length of stay, supplemental oxygen utilization, and mortality of COVID-19 infection outcomes using Rev Man version 5.3. To evaluate the validity of our studies the National Institutes of Health quality assessment tool was used. The stability of the results was assessed using sensitivity analysis.

Research results

A total of 43388 patients from thirty-two studies were included in the final analysis. There were 8538 (20%) with NAFLD/MAFLD. A total of 42475 patients from twenty-nine studies were included in the mortality analysis. There was an odds ratio of 1.36, a P value = 0.07 for mortality with COVID-19. A total of 5043 patients from eight studies were included in the hospital length of stay analysis. NAFLD patients spent a mean hospital stay of an additional about 2 d when compared to non-NAFLD. For hospitalization rates, the odds ratio is 3.25 and a P value = 0.0002. For supplemental oxygen utilization, the odds ratio was 2.04 with a P value = 0.01. Our meta-analysis was able to show that there is an association between NAFLD/MAFLD and COVID-19. Our study aims to increase awareness that NAFLD/MAFLD may be a potential risk factor for severe outcomes in infections. More research is needed to better explain the relationship and the pathophysiology behind it.

Research conclusions

This systematic review and meta-analysis of observational studies suggests that NAFLD/MAFLD patients had higher odds of developing severe forms of COVID-19 in comparison to non-NAFLD patients. Further research to understand the causality and strength of this relationship is needed.

Research perspectives

This review was not able to clarify why the association between NAFLD/MAFLD and COVID-19 was seen. Large size prospective studies with balanced confounding factors are necessary. Since the global burden of NAFLD/MAFLD is rapidly rising, understanding genetics and immunological mechanisms will help advance treatment and prevention strategies.