Advances in pharmacotherapy of NASH

Recent advances in the pharmacotherapy of Non-Alcoholic Steatohepatitis (NASH) have made significant strides towards addressing this complex. NASH, characterized by hepatic steatosis, inflammation, and fibrosis, can progress to cirrhosis and liver-related complications, highlighting the urgent need for effective treatments. Currently, no FDA-approved therapies exist, but the pipeline for NASH drugs is robust, with several promising candidates under investigation. Key developments include the emergence of targeted therapies such as FXR agonists (e.g., obeticholic acid), PPAR agonists (e.g., elafibranor, lanifibranor), GLP-1 receptor agonists (e.g., semaglutide), and ACC inhibitors (e.g., firsocostat). These drugs aim to address specific pathways involved in NASH pathogenesis, including metabolic dysfunction, inflammation, and fibrosis. Also, the concept of combination therapy is gaining traction, with the potential to more effectively manage the multifactorial nature of NASH by simultaneously targeting multiple disease mechanisms. Progress in identifying non-invasive biomarkers (cytokeratin 18) and imaging techniques (USG, MRI, MRE) has also enhanced the ability to monitor disease progression and treatment response, reducing reliance on liver biopsies. However, challenges remain, including ensuring the safety and tolerability of these therapies, managing patient heterogeneity, and addressing the regulatory hurdles that complicate drug approval, hence advances hope for effective treatment options in the near future.