Current, emerging, and potential therapies for non-alcoholic steatohepatitis

Abstract

Non-alcoholic fatty liver disease (NAFLD) has been identified as the most common chronic liver disease worldwide, with a growing incidence. NAFLD is considered the hepatic manifestation of a metabolic syndrome that emerges from multiple factors (e.g., oxidative stress, metabolic disorders, endoplasmic reticulum stress, cell death, and inflammation). Non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD, has been reported to be a leading cause of cirrhosis and hepatic carcinoma, and it is progressing rapidly. Since there is no approved pharmacotherapy for NASH, a considerable number of therapeutic targets have emerged with the deepening of the research on NASH pathogenesis. In this study, the therapeutic potential and properties of regulating metabolism, the gut microbiome, antioxidant, microRNA, inhibiting apoptosis, targeting ferroptosis, and stem cell-based therapy in NASH are reviewed and evaluated. Since the single-drug treatment of NASH is affected by individual heterogeneous responses and side effects, it is imperative to precisely carry out targeted therapy with low toxicity. Lastly, targeted therapeutic agent delivery based on exosomes is proposed in this study, such that drugs with different mechanisms can be incorporated to generate high-efficiency and low-toxicity individualized medicine.

Exercise, weight maintenance, and nonalcoholic fatty liver disease risk: a Chinese cohort study

“…Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition characterized by the accumulation of fat in liver cells’ cytoplasm ( Bellentani and Marino, 2009 ), and is considered a manifestation of metabolic syndrome in the liver ( Yang and Wang, 2023 ). In addition to liver-related consequences such as cirrhosis and hepatocellular carcinoma ( White et al, 2012 ), individuals with NAFLD, especially those with nonalcoholic steatohepatitis and fibrosis, are under an elevated risk of cardiovascular disease, cancer, diabetes, and overall death ( Kirk et al, 2009 ; Elias et al, 2010 ; Haufe et al, 2013 ; Vilar-Gomez et al, 2015 ; Ma et al, 2017 ; Mahfood Haddad et al, 2017 ; Allen et al, 2018 ; Allen et al, 2019 ).…”

Exploring the mechanism of dendrobine in treating metabolic associated fatty liver disease based on network pharmacology and experimental validation

“…The progression of MASLD to its advanced stage, non-alcoholic steatohepatitis (NASH), further escalates the risk, making it a leading precursor to cirrhosis and liver cancer. Given these grave implications, the proactive management and treatment of MASLD are paramount [ 2 ].…”

Exploring the Mechanism of Dendrobine in Treating Non-Alcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Validation

“…Moreover, NAFLD and its advanced stage, non-alcoholic steatohepatitis (NASH), are major causes of cirrhosis and liver cancer. Therefore, the active treatment of NAFLD is of great importance [2].…”