Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2021; 13(3): 270-290
Published online Mar 27, 2021. doi: 10.4254/wjh.v13.i3.270
Molecular pathways of liver regeneration: A comprehensive review
Yana V Kiseleva, Sevak Z Antonyan, Tatyana S Zharikova, Kirill A Tupikin, Dmitry V Kalinin, Yuri O Zharikov
Yana V Kiseleva, International School “Medicine of the Future”, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119435, Russia
Sevak Z Antonyan, Department of Emergency Surgical Gastroenterology, N. V. Sklifosovsky Research Institute for Emergency Medicine, Moscow 129010, Russia
Tatyana S Zharikova, Yuri O Zharikov, Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia
Kirill A Tupikin, Laboratory of Minimally Invasive Surgery, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
Dmitry V Kalinin, Pathology Department, A.V. Vishnevsky National Medical Research Center of Surgery of the Russian Ministry of Healthcare, Moscow 117997, Russia
Author contributions: Kiseleva YV and Zharikov YO wrote the paper; Zharikova TS, Antonyan SZ and Kalinin DV performed the data collection; Kiseleva YV and Typikin KA created the figures; Kiseleva YV and Zharikov YO designed and conceptualized the review.
Conflict-of-interest statement: The authors declare no conflicts of interest for this article.
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:
Corresponding author: Yuri O Zharikov, MD, PhD, Assistant Professor, Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya Street, Moscow 119048, Russia.
Received: October 23, 2020
Peer-review started: October 23, 2020
First decision: January 7, 2021
Revised: January 20, 2021
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: March 27, 2021
Processing time: 147 Days and 4.6 Hours

The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70% of its volume. Although knowledge of this phenomenon dates back to Greek mythology (the story of Prometheus), many aspects of liver regeneration are still not understood. A variety of different factors, including inflammatory cytokines, growth factors, and bile acids, promote liver regeneration and control the final size of the organ during typical regeneration, which is performed by mature hepatocytes, and during alternative regeneration, which is performed by recently identified resident stem cells called “hepatic progenitor cells”. Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass, such as in cases of chronic injury or excessive acute injury. In liver maintenance, the body mass ratio is essential for homeostasis because the liver has numerous functions; therefore, a greater understanding of this process will lead to better control of liver injuries, improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases. The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries. Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.

Keywords: Liver regeneration, Molecular pathways, Hepatic progenitor cells, Cytokines, Micro ribonucleic acid, Partial hepatectomy

Core Tip: The liver is a unique parenchymal organ with a regenerative capacity that can restore up to 70% of its volume. A variety of different factors and signaling pathways are involved in the process of liver mass regeneration during the priming, proliferative and termination phases. This review describes the types of liver regeneration, the phases of typical liver regeneration, the cell types involved in liver regeneration, the process of alternative liver regeneration, and the stem cells and micro ribonucleic acids that play roles in liver mass regeneration.