Role of the portal system in liver regeneration: From molecular mechanisms to clinical management^☆

Abstract

The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation. The portal system plays a crucial role in the dual blood supply to the liver, making it a significant factor in hepatic function. Several surgical strategies, such as portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and dual vein embolization, have highlighted the portal system's importance in liver regeneration. Following hepatectomy or liver transplantation, the hemodynamic properties of the portal system change dramatically, triggering regeneration via shear stress and the induction of hypoxia. However, excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes. Furthermore, as the importance of the gut-liver axis has gradually been revealed, the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged. From these perspectives, this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.

Keywords

Portal system / Liver regeneration / Hemodynamic properties / Gut microbiota / Therapeutic strategies

Authors’ contributions

Each author substantially contributed to this work. Hanzhi Xu, Xun Qiu, Zhoucheng Wang, Yawen Tan, and Fengqiang Gao: conceptualization, writing original draft. Kai Wang and Marcos Vinicius Perini: manuscript review and editing. Xiao Xu: supervi-sion. All authors read and approved the final manuscript.

Declaration of competing interest

The authors declare that there is no conflicts of interest.

Acknowledgements

This work was supported by The National Key Research and Development Program of China (No. 2021YFA1100504), Key Pro-gram, National Natural Science Foundation of China (No. 81930016), and The Zhejiang Provincial Natural Science Foundation (LY22H160048).

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