Hepatic Therapeutics for Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterised by excessive lipid accumulation in hepatocytes, ranging from simple steatosis to the inflammatory and fibrotic state of non-alcoholic steatohepatitis (NASH). Driven by obesity, dyslipidaemia and insulin resistance, NAFLD has become a leading cause of chronic liver disease worldwide, with significant implications for cardiovascular morbidity and liver-related mortality. Current management strategies centre on lifestyle modification and control of metabolic comorbidities, yet few pharmacological agents have achieved regulatory approval. Recent advances target key pathogenic mechanisms, including modulation of lipid metabolism through nuclear receptors (such as peroxisome proliferator-activated receptors and farnesoid X receptor), enhancement of fatty acid oxidation, suppression of de novo lipogenesis, attenuation of oxidative stress and inflammation, and restoration of mitochondrial function. Beyond single-target approaches, combination therapies and agents derived from natural products are under active investigation. The global burden of NAFLD, coupled with its progression to cirrhosis and hepatocellular carcinoma, underscores the urgent need for safe and effective hepatoprotective interventions that address the multifactorial pathophysiology of this condition.

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Hepatic Therapeutics for Non-Alcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in hepatic therapeutics for non-alcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Hepatic steatosis: Accumulation of lipid droplets within hepatocytes, defining the initial stage of NAFLD.

Non-alcoholic steatohepatitis (NASH): Progressive form of NAFLD characterised by hepatic inflammation, hepatocyte injury and varying degrees of fibrosis.

Glutathione S-transferase alpha 1 (GSTA1): Detoxifying enzyme that conjugates glutathione to electrophilic compounds, here implicated in promoting degradation of fatty acid binding protein 1.

Bicyclol: Synthetic hepatoprotective agent exhibiting anti-oxidative and anti-inflammatory properties used in experimental models of liver injury.

Peroxisome proliferator-activated receptor alpha (PPARα): Nuclear receptor that regulates genes involved in fatty acid transport and β-oxidation in hepatocytes.

References

1. Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1. International Journal of Molecular Sciences (2024).
2. Bicyclol attenuates high fat diet-induced non-alcoholic fatty liver disease/non-alcoholic steatohepatitis through modulating multiple pathways in mice. Frontiers in Pharmacology (2023).
3. Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease. Frontiers in Pharmacology (2022).