An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease
Steatotic liver disease (SLD) has been known for a long time, but our understanding of this disease has remained poor until the past decade. Despite extensive research, our ability to comprehend the etiopathogenesis and natural course of SLD is far from the desired level of comprehension. This is re...
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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2024-11-01
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| Series: | Exploration of Digestive Diseases |
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| Online Access: | https://www.explorationpub.com/Journals/edd/Article/100561 |
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| author | Shahid Habib Andrew Johnson |
| author_facet | Shahid Habib Andrew Johnson |
| author_sort | Shahid Habib |
| collection | DOAJ |
| description | Steatotic liver disease (SLD) has been known for a long time, but our understanding of this disease has remained poor until the past decade. Despite extensive research, our ability to comprehend the etiopathogenesis and natural course of SLD is far from the desired level of comprehension. This is required to develop a universally effective novel therapeutic agent. This review aims to concisely elaborate the conceptual approach and advancement in the understanding of global disease burden and etiopathogenic process, identifying the gaps and the pathophysiologic mechanism behind developing novel therapeutic agents. We searched two major databases, PubMed and Google Scholar, to identify publications related to the abovementioned topics. All publications, including original papers, reviews, and commentaries, were reviewed. Findings: Metabolic dysfunction-associated steatotic liver disease (MASLD) is not limited to obese individuals, rather, it may develop in any individual independent of weight. Visceral adiposity is strongly associated with MASLD and subsequent risks of cirrhosis, hepatocellular carcinoma, and cardiovascular disease. MASLD is associated with diabetes mellitus independent of underlying pathogenic mechanisms, and there is a bidirectional connection between MASLD and diabetes mellitus, making the situation quite challenging. Not all patients with MASLD exhibit atherogenic dyslipidemia and thus do not have a higher risk of cardiovascular disease. The overlap of these metabolic risk factors is not straightforward. There is a differential contribution of these risk factors based on age, gender, race, ethnicity, alcohol consumption, and microbiota composition. Poor dietary habits and lifestyle directly affect the microbiota, modulators, and mediators, thereby affecting the final biochemical processes leading to steatosis, steatohepatitis, fibrosis, and oncogenesis. In conclusion, MASLD is a complex and pathogenically heterogeneous disease with significant interpatient variation in the natural course and outcome. Understanding the precise mechanism of variability is the key gap and a limiting factor in the development of a novel therapeutic agent. |
| format | Article |
| id | doaj-art-50a83c05f9394d0f90970c56cab0fc0f |
| institution | Kabale University |
| issn | 2833-6321 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Digestive Diseases |
| spelling | doaj-art-50a83c05f9394d0f90970c56cab0fc0f2024-11-14T05:59:30ZengOpen Exploration Publishing Inc.Exploration of Digestive Diseases2833-63212024-11-013645947310.37349/edd.2024.00061An overview of pathogenesis of metabolic dysfunction-associated steatotic liver diseaseShahid Habib0https://orcid.org/0000-0002-4264-714XAndrew Johnson1https://orcid.org/0009-0007-7297-951XDepartment of Hepatology, Liver Institute PLLC, Tucson, AZ 85716, USADepartment of Hepatology, Liver Institute PLLC, Tucson, AZ 85716, USASteatotic liver disease (SLD) has been known for a long time, but our understanding of this disease has remained poor until the past decade. Despite extensive research, our ability to comprehend the etiopathogenesis and natural course of SLD is far from the desired level of comprehension. This is required to develop a universally effective novel therapeutic agent. This review aims to concisely elaborate the conceptual approach and advancement in the understanding of global disease burden and etiopathogenic process, identifying the gaps and the pathophysiologic mechanism behind developing novel therapeutic agents. We searched two major databases, PubMed and Google Scholar, to identify publications related to the abovementioned topics. All publications, including original papers, reviews, and commentaries, were reviewed. Findings: Metabolic dysfunction-associated steatotic liver disease (MASLD) is not limited to obese individuals, rather, it may develop in any individual independent of weight. Visceral adiposity is strongly associated with MASLD and subsequent risks of cirrhosis, hepatocellular carcinoma, and cardiovascular disease. MASLD is associated with diabetes mellitus independent of underlying pathogenic mechanisms, and there is a bidirectional connection between MASLD and diabetes mellitus, making the situation quite challenging. Not all patients with MASLD exhibit atherogenic dyslipidemia and thus do not have a higher risk of cardiovascular disease. The overlap of these metabolic risk factors is not straightforward. There is a differential contribution of these risk factors based on age, gender, race, ethnicity, alcohol consumption, and microbiota composition. Poor dietary habits and lifestyle directly affect the microbiota, modulators, and mediators, thereby affecting the final biochemical processes leading to steatosis, steatohepatitis, fibrosis, and oncogenesis. In conclusion, MASLD is a complex and pathogenically heterogeneous disease with significant interpatient variation in the natural course and outcome. Understanding the precise mechanism of variability is the key gap and a limiting factor in the development of a novel therapeutic agent.https://www.explorationpub.com/Journals/edd/Article/100561metabolic dysfunctions-associated steatotic liver disease (masld)visceral adiposityobesitypathogenesis |
| spellingShingle | Shahid Habib Andrew Johnson An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease Exploration of Digestive Diseases metabolic dysfunctions-associated steatotic liver disease (masld) visceral adiposity obesity pathogenesis |
| title | An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease |
| title_full | An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease |
| title_fullStr | An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease |
| title_full_unstemmed | An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease |
| title_short | An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease |
| title_sort | overview of pathogenesis of metabolic dysfunction associated steatotic liver disease |
| topic | metabolic dysfunctions-associated steatotic liver disease (masld) visceral adiposity obesity pathogenesis |
| url | https://www.explorationpub.com/Journals/edd/Article/100561 |
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