The Potential and Challenges of Autophagy in the Treatment of Liver Fibrosis

Recently, we carefully read a research article published in Liver International by Li-Shuang Hou et al. [1]. The study proposes a novel therapeutic strategy for liver fibrosis by targeting and inhibiting the autophagic process in hepatic stellate cells. The study utilised hydroxychloroquine (HCQ)-loaded liposome nanoparticles (HCQ@ROL-LNPs) to show selective inhibition of autophagy in activated hepatic stellate cells (aHSCs), which provides a new idea for liver fibrosis treatment. Autophagy is an important mechanism for cleaning and recycling damaged components inside the cell [2]. In liver fibrosis, aberrant activation of autophagy is closely associated with activation of hepatic stellate cells and extracellular matrix deposition [3]. HCQ@ROL-LNPs show the potential to reduce extracellular matrix deposition and protect other hepatocytes by targeting aHSCs, which holds promise for the treatment of liver fibrosis. However, despite the innovative nature of this discovery, there are still some drawbacks and shortcomings before translating it into clinical applications. Firstly, the dose–response relationship of a drug is essential to ensure therapeutic efficacy, reduce side effects, individualise treatment, optimise dosage, reduce healthcare costs and guide clinical use [4, 5]. It contributes to drug development, dosage optimisation, economic considerations and safety assessment for long-term treatment. The dose–response relationship of HCQ@ROL-LNPs was not examined in the study. In addition, the efficacy and potential side effects of HCQ@ROL-LNPs after long-term administration may not have been explored in detail in this study. More importantly, HCQ@ROL-LNPs efficacy was only examined in mice in the study, and it remains questionable whether it has similar activity in other species. In summary, although HCQ@ROL-LNPs offer a novel strategy for liver fibrosis treatment, several challenges still need to be overcome before they become a clinical reality. Future studies need to further examine the quantitative and efficacy relationships and extend them to other species to validate their efficacy and safety, as well as to explore their mechanism of action in depth. Only then will we be able to fully utilise the potential of autophagy in the treatment of liver fibrosis and bring more effective therapeutic options to patients! The authors declare no conflicts of interest. The authors have nothing to report.