Korchilava B, Khachidze T, Megrelishvili N, Svanadze L, Kakabadze M, Tsomaia K, Jintcharadze M, Kordzaia D. Liver regeneration after partial hepatectomy: Triggers and mechanisms. World J Hepatol 2025; 17(7): 107378 [DOI: 10.4254/wjh.v17.i7.107378]
Corresponding Author of This Article
Dimitri Kordzaia, MD, PhD, Professor, Alexandre Natishvili Institute of Morphology, Ivane Javakhishvili Tbilisi State University, Beliashvili Street 78, Tbilisi 0159, Georgia. dimitri.kordzaia@tsu.ge
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Opinion Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bakari Korchilava, Department of Clinical Anatomy and Operative Surgery, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
Tamar Khachidze, Department of Clinical Anatomy, Tbilisi State Medical University, Tbilisi 0130, Georgia
Nino Megrelishvili, Department of Pathology, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
Lika Svanadze, Manana Kakabadze, Keti Tsomaia, Dimitri Kordzaia, Alexandre Natishvili Institute of Morphology, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
Memed Jintcharadze, Department of Oncosurgery, Batumi High-Tech Hospital, Medical Center, Batumi 6000, Ajaria, Georgia
Author contributions: Korchilava B, Gvidiani S, Jintcharadze M and Kordzaia D contributed substantially to the review article's conception and design; Drafting the article or providing critical revisions related to the important intellectual content of the manuscript was carried out by Korchilava B, Gvidiani S, Megrelishvili N, Svanadze L, Kakabadze M, Tsomaia K, Khachidze T, and Kordzaia D; Responses to the reviewers were prepared by Kordzaia D, Svanadze L, Korchilava B and Khachidze T and the final version was discussed and approved by all authors; Provision of final approval for the version of the article to be published was provided by Korchilava B, Gvidiani S, Svanadze L, Tsomaia K and Kordzaia D; All authors have made significant contributions to this paper and have approved.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dimitri Kordzaia, MD, PhD, Professor, Alexandre Natishvili Institute of Morphology, Ivane Javakhishvili Tbilisi State University, Beliashvili Street 78, Tbilisi 0159, Georgia. dimitri.kordzaia@tsu.ge
Received: March 26, 2025 Revised: April 23, 2025 Accepted: June 10, 2025 Published online: July 27, 2025 Processing time: 121 Days and 18.1 Hours
Abstract
Liver regeneration (LR) following partial hepatectomy (PH) is a unique and complex physiological response that restores hepatic mass and function through tightly orchestrated cellular and molecular events. Traditionally viewed as a proliferation-driven process, LR is now understood to involve both hepatocyte hyperplasia and hypertrophy, triggered primarily by hemodynamic alterations such as increased portal pressure and shear stress. These promote LR through endothelial–hepatocyte communication via activation of Piezo1 - a mechanosensitive ion channel highly expressed in vascular endothelial cells. This channel is considered one of the potential upstream activators of molecular cascades including the interleukin (IL)-6/signal transducer and activator of transcription 3, tumour necrosis factor-alpha/nuclear factor-kappa B, Wnt/β-catenin, Hippo/ YAP, transforming growth factor-beta, and Notch pathways, which contribute variably to the proliferation, differentiation, or suppression of hepatic cells. Novel insights into the IL-22 and IL-33 signaling axes, bile acid and glutamine metabolism, and the role of intestinal microbiota are also presented as promising emerging targets. This review synthesizes current insights into the interplay between mechanical cues, key signaling pathways, and metabolic reprogramming that govern early regenerative responses. We explore the mechanisms dictating the balance between hyperplasia and hypertrophy, noting that hypertrophy predominates after minor resections, while proliferation is dominant in larger resections. Polyploidization emerges as a significant adaptive mechanism, contributing to hepatocyte survival and tissue remodeling. The importance of ductular reactions, microvascular adjustments, and extracellular matrix dynamics in lobular architecture remodeling is also highlighted. The study explores the occurrence of ductular reactions in both minor and major resections, particularly within the granulation tissue near dissection areas. The paper also examines structural remodeling in regenerated liver tissue, demonstrating ongoing transformations in hepatocyte morphology and sinusoidal architecture even months after PH, and emphasizing that the termination of liver mass regrowth does not equate to the cessation of LR.
Core Tip: This review synthesizes key triggers and molecular pathways of Liver regeneration after partial hepatectomy, emphasizing the central role of portal hemodynamics, cytokine signaling, and extracellular matrix remodeling. It highlights underexplored processes such as ductular reaction in granulation tissue, and the role of metabolic regulators like bile acids and glutamine. The paper outlines mechanisms of the termination of liver regenerative and proposes new perspectives for its therapeutic modulation in clinical settings.
