A Comprehensive Systematic Review on Therapeutic Discovery of NAFLD Drugs

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders not linked to excessive alcohol consumption. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma (HCC). As NAFLD is closely associated with metabolic dysregulation, a shift in terminology to metabolic associated fatty liver disease (MAFLD) has been suggested. Despite its global rise in prevalence, there are currently no pharmacological treatments for NAFLD, necessitating exploration of therapeutic pathways.

This review aims to systematically analyze current therapeutic options for NAFLD, including allopathic and herbal remedies, to identify potential future directions for drug discovery. Emphasis is placed on understanding marketed hepatoprotective and anti-obesity drugs, exploring the integration of traditional Ayurvedic approaches with modern allopathic therapies.

A comprehensive search was conducted across multiple databases, including PubMed, Scopus, Web of Science, and clinical trial registries. The search terms used were “NAFLD,” “NASH,” “therapeutic discovery,” “drug development,” “hepatoprotective drugs,” “anti-inflammatory drugs,” “herbal medicine,” “Ayurvedic medicine,” and “anti-obesity drugs.” The search was limited to studies published in English between 2000 and 2024 to capture recent advancements in the field. Additional manual searches were performed by reviewing the reference lists of relevant studies and reviewing abstracts from major hepatology and pharmacology conferences.

The analysis highlights the absence of universally effective pharmacological treatments for NAFLD. While current allopathic drugs target specific pathways such as inflammation and fibrosis, their efficacy remains limited. Herbal and Ayurvedic treatments, though widely marketed as hepatoprotective, lack sufficient clinical validation. Combining allopathic and traditional approaches may offer a promising avenue for developing comprehensive treatment strategies.

The increasing prevalence of NAFLD calls for innovative therapeutic strategies that bridge the gap between traditional medicine and modern drug discovery. Future research should focus on targeted anti-inflammatory therapies and multi-faceted treatment approaches that incorporate both allopathic and herbal/Ayurvedic remedies. Such integration could accelerate the discovery of effective treatments, improving patient outcomes in NAFLD management.