Response to the Potential and Challenges of Autophagy in the Treatment of Liver Fibrosis

We thank Dr. Jia Chen and Qichang Xing for their interest in the article published in Liver International about the research on targeted delivery system HCQ@ROL-LNPs loaded with hydroxychloroquine (HCQ) for the treatment of liver fibrosis [1]. HCQ@ROL-LNPs can be uptaken specifically by activated hepatic stellate cells (aHSCs) and inhibit the autophagy of aHSCs to improve liver fibrosis. As mentioned by the authors [2], autophagy of different types of liver cells has different effects on liver fibrosis [3]. HCQ@ROL-LNPs can reduce the activation and extracellular matrix deposition by targeting aHSCs, and at the same time avoid the influence on other types of liver cells, which is well situated to treat liver fibrosis. It is very necessary to verify the dose–response relationship of drugs before they are transformed into clinical applications [4]. This paper is a delivery system study, in which the dose of HCQ was on the basis of previous screening experiments [5]. The dose–response relationship and the therapeutic effect after long-term administration will continue to be studied in the follow-up experiment. The previous research was mainly to validate the efficacy in mice, and it is also very necessary to verify the therapeutic effect in other species before entering clinical trials. The constructed HCQ@ROL-LNPs provides a new targeted strategy by using autophagy inhibition of aHSCs for the treatment of liver fibrosis. Before it is used in clinic, it is still necessary to conduct extensive research to verify its potential efficacy and therapeutic safety, which will provide the evidence for the clinical use of antiliver fibrosis drugs in the future. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no data sets were generated or analysed during the current study.