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World J Stem Cells. Oct 26, 2020; 12(10): 1124-1132
Published online Oct 26, 2020. doi: 10.4252/wjsc.v12.i10.1124
Still 'dwelling in the possibility' - critical update on stem cell therapy for acute on chronic liver failure
Cyriac Abby Philips, Philip Augustine
Cyriac Abby Philips, The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682025, Kerala, India
Philip Augustine, Department of Gastroenterology and Advanced GI Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682025, Kerala, India
Author contributions: Philips CA designed and wrote the original draft and was involved in the revision; Augustine P was involved in the editing and review of the manuscript; all authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interests 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cyriac Abby Philips, MD, DM, Consultant Physician Scientist, The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, NH Bypass, Palarivattom, Kochi 682025, Kerala, India. abbyphilips@gmail.com
Received: May 24, 2020
Peer-review started: May 24, 2020
First decision: August 22, 2020
Revised: August 29, 2020
Accepted: September 22, 2020
Article in press: September 22, 2020
Published online: October 26, 2020
Processing time: 155 Days and 4.9 Hours
Abstract

Stem cells therapy could improve survival in patients with liver failure. Studies on stem cell therapy and related growth factors in decompensated cirrhosis has been on the forefront but has shown heterogenous results. Recent high-quality studies have shown a lack of efficacy and safety. Patients with acute-on-chronic liver failure (ACLF) are a unique group with high mortality in the short-term associated with rapid onset extrahepatic organ failures. In these patients, there is an urgent need to identify treatments that can improve liver cell function and mass, prevent sepsis/organ failure, ameliorate systemic inflammation, and increase transplant-free survival. Stem cells are a novel treatment in ACLF but with unclear efficacy and safety. In this narrative review, we discuss the basics of liver regeneration in patients with ACLF and update current clinical status of stem cell use in patients with ACLF for improving our understanding of future directions.

Keywords: Portal hypertension; Regenerative therapy; Mesenchymal stem cells; Liver failure; Sepsis

Core Tip: In patients with acute on chronic liver failure (ACLF), the efficacy and safety of stem cell therapy remains unclear because there are few adequately powered, high-quality studies. Most studies in ACLF have been performed in Asian centers and in those with hepatitis B virus infection. Some studies have demonstrated improved short-term survival as well as liver disease severity and better hepatic synthetic and excretory functions. However, long term clinical efficacy and safety as well as ideal protocols for stem cell extraction, dose, duration, route, and type, in patients with ACLF remain unclear and requires sufficiently powered studies.