Steatotic liver disease (SLD) is a leading cause of disease globally and demands new therapeutic approaches to mitigate underlying metabolic dysregulation. Incretin-based therapies are emerging as a viable prospect to fulfil this unmet niche. A literature review to inform the evidence base for incretin focussed pharmacology in the metabolic liver diseases space and an informed commentary on unmet areas of need. Incretin-based therapeutics demonstrate multifarious benefits across the chronic metabolic disease spectrum with promising data across the continuum of pathology.
Associations between systemic inflammatory biomarkers and metabolic dysfunction associated steatotic liver disease: a cross-sectional study of NHANES 2017–2020 Xin Qiu, Shuang Shen, Nizhen Jiang, Yifei Feng, Guodong Yang, Donghong Lu BMC Gastroenterology.2025;[Epub] CrossRef
Correspondence to letter to the editor 2 on “Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study” Seogsong Jeong, Won Kim, Sang Min Park Clinical and Molecular Hepatology.2025; 31(2): e210. CrossRef
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex multifactorial disease and becoming the leading cause of liver-related morbidity and mortality. MASLD spans from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may progress to cirrhosis and hepatocellular carcinoma (HCC). Genetic, metabolic, and environmental factors strongly contribute to the heterogeneity of MASLD. Lifestyle intervention and weight loss represent a viable treatment for MASLD. Moreover, Resmetirom, a thyroid hormone beta receptor agonist, has recently been approved for MASLD treatment. However, most individuals treated did not respond to this therapeutic, suggesting the need for a more tailored approach to treat MASLD. Oligonucleotide-based therapies, namely small-interfering RNA (siRNA) and antisense oligonucleotide (ASO), have been recently developed to tackle MASLD by reducing the expression of genes influencing MASH progression, such as PNPLA3 and HSD17B13. Here, we review the latest progress made in the synthesis and development of oligonucleotide-based agents targeting genetic determinants of MASH.
Unveiling EMC6 as a novel pathogenic determinant in hepatocellular carcinoma: orchestration of lipid metabolism through regulation of lipid droplet-associated enzyme HSD17B13 Yun Zhang, Chanyu Xiong, Zhilin Jiang, Xiao Wang, Zihao Wang, Junyao Chen, Qiong Li, Yangyang Luo, Xudan Yang, Chen Chu, Shikai Zhu, Xianjun Zhu, Yu Zhou Oncogene.2026; 45(2): 322. CrossRef
Cholesterol-dependent control of endosomal escape regulates intracellular trafficking of small interfering RNA therapeutics and interactions with small molecule drugs Sherouk M. Tawfik, Le Tra Giang Nguyen, Jing Jin, Beshoy Armanios, Xiao-bo Zhong The Journal of Pharmacology and Experimental Therapeutics.2026; 393(2): 103802. CrossRef
Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation Senping Xu, Zhaoshan Zhang, Zhongquan Zhou, Jiawei Guo Biology.2026; 15(2): 148. CrossRef
Rodent model of metabolic dysfunction‐associated fatty liver disease: a systematic review Xiao‐Shan Cui, Hong‐Zheng Li, Liang Li, Cheng‐Zhi Xie, Jia‐Ming Gao, Yuan‐Yuan Chen, Hui‐Yu Zhang, Wei Hao, Jian‐Hua Fu, Hao Guo Journal of Gastroenterology and Hepatology.2025; 40(1): 48. CrossRef
Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk Maria Castanho Martins, Emmanuel Dauda Dixon, Giulia Lupo, Thierry Claudel, Michael Trauner, Krista Rombouts Liver International.2025;[Epub] CrossRef
Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative Review Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroyuki Abe, Naruhiro Kimura, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai International Journal of Molecular Sciences.2025; 26(11): 5164. CrossRef
Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation Yiwei Lu, Tong Ji, Zhichao Ye, Jianing Yan, Chao Wang, Jiachen Chen, Ziyang Jin, Yongji Zhu, Xiujun Cai, Yifan Wang Advanced Science.2025;[Epub] CrossRef
Emerging therapies and real-world application of metabolic dysfunction-associated steatotic liver disease treatment Hee Yeon Kim, Mary E. Rinella Clinical and Molecular Hepatology.2025; 31(3): 753. CrossRef
Multi-omics reveals total flavones from Abelmoschus manihot (L.) Medik. [Malvaceae] ameliorate MAFLD via PI3K/AKT/mTOR-mediated autophagy Chao Lv, Lei Zhao, Jiani Hou, Hongyin Sun, Zhongsha Li, Yuesong Wu, Peizheng Shi, Yaping Xiao, Yunjin Xie, Wei Su, Mingzhu Yin Frontiers in Pharmacology.2025;[Epub] CrossRef
The Distribution and Survival Association of Genetic Polymorphisms in Thai Patients with Hepatocellular Carcinoma According to Underlying Liver Disease Theint Cho Zin Aung, Bootsakorn Boonkaew, Maneerat Chayanupatkul, Kittiyod Poovorawan, Natthaya Chuaypen, Pisit Tangkijvanich Genes.2025; 16(7): 808. CrossRef
Editorial: Time to Genotype—Genetic Risk and Prognosis in Steatotic Liver Disease Rosellina M. Mancina, Stefano Romeo Alimentary Pharmacology & Therapeutics.2025; 62(8): 841. CrossRef
Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism Rosellina M. Mancina, Luca Valenti, Stefano Romeo Nature Metabolism.2025; 7(11): 2199. CrossRef
Lysosome-Targeting Chimeras: Design, Mechanisms, and Degradation of “Rogue” Proteins Muneeb Ur Rehman, Xinxi Wu, Qun Chen, Ziwei Liu, Sihui Long Bioorganic Chemistry.2025; 167: 109249. CrossRef
Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances Liangtao Zhao, Haolan Tang, Zhangjun Cheng Pharmaceuticals.2024; 17(12): 1724. CrossRef
Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.
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“Metabolic dysfunction-associated fatty liver disease (MAFLD)” is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.
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