Mammalian target of rapamycin in chronic liver disease and the potential for therapeutic manipulation

Chronic Liver Disease (CLD) represents a growing epidemic in the Western world, yet treatment options that effectively slow its progression remain limited. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus (also known as rapamycin), have been proposed as potential antifibrotic agents over the past decade; however, their role in chronic liver disease remains underexplored. mTOR is a protein kinase integral to a key cellular pathway, which is essential for normal liver physiology but is also implicated in the pathogenesis of CLD and hepatocellular carcinoma (HCC). This narrative review summarises the role of mTOR in the healthy liver, its dysregulation across common aetiologies of CLD, and its role in HCC. An electronic literature search of Ovid MEDLINE was conducted from database inception to 2025 to identify studies evaluating the role of MTOR in CLD. The review underscores a clear unmet need for well-designed human clinical trials to specifically assess mTOR inhibitors as potential anti-fibrotic therapies.