Liver Regeneration after Acetaminophen Hepatotoxicity: Mechanisms and Therapeutic Opportunities.

Abstract

Acetaminophen (N-acetyl-para-aminophenol; APAP) overdose is the most common cause of acute liver failure in the Western world, with limited treatment opportunities. For years, research on APAP overdose has been focused on investigating the mechanisms of hepatotoxicity, with limited success in advancing therapeutic strategies. Acute liver injury after any insult, including APAP overdose, is followed by compensatory liver regeneration, which promotes recovery and is a crucial determinant of the final outcome. Liver regeneration after APAP-induced liver injury is dose dependent and impaired after severe APAP overdose. Although robust regenerative response is associated with spontaneous recovery and survival, impaired regeneration results in faster progression of injury and death after APAP overdose. APAP hepatotoxicity-induced liver regeneration involves a complex time- and dose-dependent interplay of several signaling mediators, including growth factors, cytokines, angiogenic factors, and other mitogenic pathways. Compared with the liver injury, which is established before most patients seek medical attention and has proved difficult to manipulate, liver regeneration can be potentially modulated even in late-stage APAP-induced acute liver failure. Despite recent efforts to study the mechanisms of liver regeneration after APAP-induced liver injury, more comprehensive research in this area is required, especially regarding factors that contribute to impaired regenerative response, to develop novel regenerative therapies for APAP-induced acute liver failure.

• Authors: Bharat Bhushan, Udayan Apte
• Journal: The American journal of pathology (Am J Pathol) Vol. 189 Issue 4 Pg. 719-729 (04 2019) ISSN: 1525-2191 [Electronic] United States
• PMID: 30653954 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Analgesics, Non-Narcotic
• Acetaminophen

Topics

• Acetaminophen (adverse effects)
• Analgesics, Non-Narcotic (adverse effects)
• Chemical and Drug Induced Liver Injury (etiology, prevention & control)
• Drug Overdose (complications)
• Humans
• Liver Failure, Acute (chemically induced)
• Liver Regeneration (drug effects)