Longitudinal Clinical Outcomes and Mortality from Steatotic Liver Disease: A Meta-Analysis

Do Han Kim MD, Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Donghyun Ko, Department of Internal Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, CT, USA.
Pojsakorn Danpanichkul, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Gleen Jun Kit Ho, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Faith Xin Ning Tan, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
N Apoorva Sasikumar, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Ethan Kai Jun Tham, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Daniel Q. Huang, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital Singapore, Singapore.
Nicholas Syn, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: nicholassyn@gmail.com.
Ming-Hua Zheng, MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Wenzhou Key Laboratory of Hepatology, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease, Zhejiang, Wenzhou, China.
Takumi Kawaguchi, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. Electronic address: takumi@med.kurume-u.ac.jp.
Yoshio Sumida, Graduate School of Healthcare Management, International University of Healthcare and Welfare, Narita, Japan.
Atsushi Nakajima, Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: nakajima-tky@umin.ac.jp.
Hirokazu Takahashi, Division of Metabolism and Endocrinology, Department of Medicine, Faculty of Medicine, Saga University, Saga, Japan. Electronic address: takahas2@cc.saga-u.ac.jp.
Mazen Noureddin, Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cheng Han NG, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital Singapore, Singapore.
Mark D. Muthiah, Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital Singapore, Singapore. Electronic address: mdcmdm@nus.edu.sg.
Karn Wijarnpreecha, Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, USA.

Document Type

Article

Publication Title

American Journal of Medicine

Abstract

Introduction: The updated consensus introduces "steatotic liver disease" as an umbrella term for all patients with hepatic steatosis, with specific subtypes such as metabolic dysfunction-associated steatotic liver disease (MASLD), MetALD (MASLD with moderate alcohol intake), and alcohol-associated liver disease. Understanding the characteristics and long-term outcomes of these subtypes is essential.

Methods: A systematic review and meta-analysis examined studies published between January 2023 and August 2024 in MEDLINE and EMBASE on liver-related events, cardiovascular outcomes, and mortality across steatotic liver disease subtypes.

Results: A total of 13 studies, involving 17.6 million patients were included. Of these, 6.8 million individuals were diagnosed with steatotic liver disease. Subtype analysis revealed a significant increase in liver-related events and composite cardiovascular outcomes across all steatotic liver disease subtypes compared to non-steatotic liver disease. Patients with MetALD and alcohol-associated liver disease were associated with a higher risk of all-cause mortality when compared to non-steatotic liver disease. Compared to MASLD, patients with MetALD and alcohol-associated liver disease significantly elevated the risk of liver-related events and individuals with alcohol-associated liver disease were associated with increased risk of all-cause mortality. Sensitivity analysis demonstrated that certain mortality outcomes were no longer significant.

Conclusion: Individuals across steatotic liver disease face an elevated risk of liver-related events, liver cancer, and cardiovascular outcomes. For liver-related events, the risk is progressively higher across MASLD, MetALD, and alcohol-associated liver disease, respectively. Misclassification may be introduced when using different diagnostic methods, leading to changes in outcomes. These findings validate the impact of the new classification in predicting outcomes.

Publication Date

4-30-2025

e-ISSN

1555-7162

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