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Metabolic dysfunction-associated steatotic liver disease (MASLD): Exploring systemic impacts and innovative therapies - 03/04/25

Doi : 10.1016/j.clinre.2025.102584 
Parag Jain a, , Akanksha Jain b, Rohitas Deshmukh c, Pradeep Samal d, Trilochan Satapathy e,  Ajazuddin a
a Department of Pharmacology, Rungta College of Pharmaceutical Sciences and Research, Bhilai, C.G., India, 490024 
b Department of Biotechnology, Bharti University, Durg, C.G., India 
c Institute of Pharmaceutical Research, GLA University, Mathura, India, 281406 
d Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, C.G., India 
e Department of Pharmacy, Columbia Institute of Pharmaceutical Sciences, Raipur, C.G., India, 493111 

Corresponding author at: Department of Pharmacology, Rungta College of Pharmaceutical Sciences and Research, Bhilai, C.G., India – 490024.Department of Pharmacology, Rungta College of Pharmaceutical Sciences and ResearchBhilaiC.G.490024India

Highlights

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes the inflammatory subtype metabolic dysfunction-associated steatohepatitis.
Insulin resistance, obesity, and dyslipidaemia produce MASLD in over 30 % of adults.
Hepatic inflammation and fibrosis progress from MASLD to MASH, eventually leading to cirrhosis, hepatocellular carcinoma, cardiovascular disease, chronic kidney disease and sarcopenia.
Pioglitazone, an SGLT-2 inhibitor, and GLP-1 receptor agonists have shown encouraging results in the treatment of metabolic dysfunction.
Lifestyle modification is considered as the main management of MASLD currently.

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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), which includes the inflammatory subtype metabolic dysfunction-associated steatohepatitis, is a prominent cause of chronic liver disease with systemic effects. Insulin resistance, obesity, and dyslipidaemia produce MASLD in over 30 % of adults. It is a global health issue. From MASLD to MASH, hepatic inflammation and fibrosis grow, leading to cirrhosis, hepatocellular cancer, and extrahepatic complications such CVD, CKD, and sarcopenia. Effects of MASLD to MASH are mediated through mechanisms that include inflammation, oxidative stress, dysbiosis, and predisposition through genetic makeup. Advances in diagnostic nomenclature in the past few years have moved the emphasis away from NAFLD to MASLD, focusing on the metabolic etiology and away from the stigma of an alcoholic-related condition. Epidemiological data show a large geographical variability and increasing prevalence in younger populations, particularly in regions with high carbohydrate-rich diets and central adiposity. Lifestyle modification is considered as the main management of MASLD currently. This may include dietary intervention, exercise, and weight loss management. Pharmaceutical management is primarily aimed at metabolic dysfunction with promising findings for GLP-1 receptor agonists, pioglitazone and SGLT-2 inhibitors, which can correct both hepatic and systemic outcome. However, it still depends on well-integrated multidisciplinary care models by considering complex relationships between MASLD and its effects on extrahepatic organs. Determining complications at an early stage; developing precision medicine strategies; exploring new therapeutic targets will represent crucial factors in improving their outcomes. This review discuss the systemic nature of MASLD and calls for multiple collaborations to reduce its far-reaching health impacts and our quest for understanding its pathological mechanisms. Thus, collective efforts that are required to address MASLD are under the public health, clinical care, and research angles toward effectively containing its rapidly increasing burden.

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Keywords : MASLD, NASH, Diabetes, Kidney disease, Steatosis, Adiposity


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Vol 49 - N° 6

Artículo 102584- juin 2025 Regresar al número
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