Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2024; 16(1): 54-64
Published online Jan 27, 2024. doi: 10.4254/wjh.v16.i1.54
Metabolic puzzle: Exploring liver fibrosis differences in Asian metabolic-associated fatty liver disease subtypes
Sabhita Shabir Shaikh, Fakhar Ali Qazi-Arisar, Saba Nafay, Sidra Zaheer, Hafeezullah Shaikh, Zahid Azam
Sabhita Shabir Shaikh, Fakhar Ali Qazi-Arisar, Saba Nafay, Hafeezullah Shaikh, Zahid Azam, National Institute of Liver and GI Diseases, Dow University of Health Sciences, Sindh, Karachi 75330, Pakistan
Sidra Zaheer, School of Public Health, Dow University of Health Sciences, Sindh, Karachi 75330, Pakistan
Author contributions: Shaikh SS designed the research study; Shaikh SS and Nafay S participated in the data acquisition; Shaikh SS and Zaheer S participated in the analysis and interpretation of the data; Shaikh SS and Qazi-Arisar FA drafted the initial manuscript; Qazi-Arisar FA, Shaikh H, and Azam Z revised the article critically for important intellectual content.
Institutional review board statement: The study was reviewed and approved by the Dow University of Health Sciences Institutional Review Board (IRB-1842).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fakhar Ali Qazi-Arisar, FACP, FCPS, FRCP, MBBS, MRCP, Assistant Professor, National Institute of Liver and GI Diseases, Dow University of Health Sciences, Suparco Road, Gulzar-e-Hijri, Scheme 33, Sindh, Karachi 75330, Pakistan. fakhar.arisar@gmail.com
Received: October 2, 2023
Peer-review started: October 2, 2023
First decision: October 9, 2023
Revised: October 22, 2023
Accepted: December 18, 2023
Article in press: December 18, 2023
Published online: January 27, 2024
Research background

Metabolic-associated fatty liver disease (MAFLD) is a medical condition characterized by the presence of fatty liver along with overweight/obesity and/or diabetes and/or metabolic dysfunction. However, whether the subtypes of MAFLD based on the metabolic disorder differentially impact on liver fibrosis is not well explicated, especially in the Asian population.

Research motivation

Different subgroups of MAFLD present distinct clinical spectra and risks of advanced liver fibrosis, which can influence their treatment strategies. Metabolic syndrome is related to higher deaths in nonalcoholic fatty liver disease (NAFLD) patients. Moreover, the high fibrotic burden in fatty liver disease is associated with a higher risk of development of hepatocellular carcinoma, liver-related mortality, and cardiovascular disease. Hence, it is worth classifying the MAFLD patients depending on the number of metabolic conditions at the beginning. This helps to stratify patients with MAFLD according to the long-term risk of significant liver fibrosis.

Research objectives

To compare the severity of liver fibrosis among different MAFLD subtypes.

Research methods

This was a cross-sectional investigation carried out at the National Institute of Liver and GI Diseases, located at Dow University Hospital in Karachi, Pakistan. All patients aged between 18 and 65 years, irrespective of gender, who were diagnosed with fatty liver between January and December 2021 were included. Patients with decompensated liver disease, hepatocellular carcinoma, acute hepatitis, acute-on-chronic liver disease, and other concomitant liver disease (chronic active viral, alcohol, autoimmune, or metabolic liver diseases) were excluded. Pregnant or lactating female patients and patients with concomitant systemic diseases such as tuberculosis, autoimmune disorders, and extra-hepatic malignancies were also excluded from the study. MAFLD was defined according to the Asia Pacific Association for the Study of the Liver guidelines, and fibrosis-4 index (Fib-4) and NAFLD fibrosis score (NFS) were used to assess liver fibrosis. Asian cutoffs were used for body mass index to classify the subjects into overweight/obese vs lean/normal weight MAFLD groups.

Research results

Out of 322 patients with fatty liver, 273 were classified as having MAFLD. The MAFLD patients were segregated into three categories according to their number of metabolic conditions (i.e., one, two, and three). Out of 273 participants with MAFLD, 110 (40.3%) carried a single metabolic condition, 129 (47.3%) had two metabolic conditions, and 34 (12.5%) had all the three metabolic conditions. The proportion of significant fibrosis increased with the cumulative number of metabolic conditions. For the NFS score, advanced fibrosis was 4.1%, 25.5%, 35.6%, and 44.1% for no MAFLD and MAFLD with 1, 2, and 3 conditions, respectively, while for Fib-4 score, the proportion of advanced fibrosis was 6.1%, 10.9%, 17%, and 26.5% for no MAFLD and MAFLD with 1, 2, and 3 conditions, respectively. Furthermore, MAFLD patients with a single metabolic condition (n = 110, 40.3%) were sub-classified into three categories: Obesity alone (n = 61, 55.5%), lean metabolic dysfunction (MD) (n = 34, 30.9%), and diabetes mellitus (DM) alone (n = 15, 13.6%). When compared among the three subtypes of MAFLD, the proportion of advanced liver fibrosis was significantly higher among diabetic MAFLD patients according to the NFS score (46.6% vs 26.5% for MD alone and 19.7% for obesity alone), whereas patients with lean MD had the highest proportion of advanced fibrosis according to the Fib-4 score (14.7% vs 9.8% for obesity alone vs 6.7% for DM alone).

Research conclusions

The increased number of metabolic conditions increases the likelihood of fibrosis in patients with MAFLD. The severity of liver fibrosis varies among different subtypes of MAFLD. Patients with diabetes and MAFLD have the highest risk of developing fibrosis.

Research perspectives

The direction of future research in this area involves several key questions that need to be addressed. Investigating the specific diagnostic markers for different subgroups within MAFLD, such as those with obesity, lean individuals, and those with type 2 diabetes. Further exploration is needed regarding the pathogenesis of MAFLD/metabolic dysfunction-associated steatohepatitis (MASH). By conducting thorough investigations into these areas, researchers can gain a better understanding of the complexities surrounding non-alcoholic fatty liver disease and its associated MD. Future research should focus on identifying effective pharmacotherapeutic interventions for MAFLD/MASH, as there is currently no approved treatment for this condition.