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Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease
Open accessAbstract
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches based on a profound understanding of its pathogenesis to halt disease progression to advanced fibrosis or cirrhosis and cancer. The pathogenesis of NAFLD involves a complex interaction among environmental factors (i.e., Western diet), obesity, changes in microbiota, and predisposing genetic variants resulting in a disturbed lipid homeostasis and an excessive accumulation of triglycerides and other lipid species in hepatocytes. Insulin resistance is a central mechanism that leads to lipotoxicity, endoplasmic reticulum stress, disturbed autophagy, and, ultimately, hepatocyte injury and death that triggers hepatic inflammation, hepatic stellate cell activation, and progressive fibrogenesis, thus driving disease progression. In the present review, we summarize the currently available data on the pathogenesis of NAFLD, emphasizing the most recent advances. A better understanding of NAFLD/NASH pathogenesis is crucial for the design of new and efficient therapeutic interventions.
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“BAs have emerged as important pathogenetic factors and therapeutic targets in both cholestatic and metabolic liver diseases.4 13 41”
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The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease
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Metadata
- Authors
- Arab, J. P., Arrese, M., & Trauner, M.
- Affiliations
- Mayo Clinic (US)
- Pontificia Universidad Católica de Chile (CL)
- Medical University of Vienna (AT)
- Corresponding author
- Trauner, Michael
- Venue
- Annual Review of Pathology Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2018-01-24
- Volume
- 13
- Issue
- 1
- Pages
- 321-350
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- OpenAlex
- W2785779482
- Cited by
- 573
- References
- 218
- Citations by year
- 2026: 43 · 2025: 64 · 2024: 76 · 2023: 85 · 2022: 61 · 2021: 93 · 2020: 77 · 2019: 47 · 2018: 26
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Association for the Study of Liver Diseases
- Vienna Science and Technology Fund
- Austrian Science Fund (F3008‐B19, F3517-B20, F3008, F3517)
- Fondo Nacional de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, pathogenesis, insulin resistance, lipotoxicity, endoplasmic reticulum stress, autophagy, liver inflammation, hepatic stellate cell activation, liver fibrosis, liver cirrhosis, hepatic lipid accumulation, gut microbiota, obesity, Western diet, genetic variants, cardiometabolic risk
- MeSH terms
- Animals, Humans, Non-alcoholic Fatty Liver Disease
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