Liver Regeneration after Acetaminophen Hepatotoxicity
Open accessAbstract
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.
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The liver has a unique ability to regenerate.
“The liver has a unique ability to regenerate1,2”
From Multimodal decoding of human liver regeneration (2024) · cites this paper as [2]
Hepatocyte proliferation has previously been considered a major driver of hepatic wound closure following necro-inflammatory liver injury.
“Hepatocyte proliferation has previously been considered a major driver of hepatic wound closure following necro-inflammatory liver injury2,24,25”
From Multimodal decoding of human liver regeneration (2024) · cites this paper as [2]
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- Authors
- Bhushan, B., & Apte, U.
- Affiliations
- University of Pittsburgh (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Apte, Udayan
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 189
- Issue
- 4
- Pages
- 719-729
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC6446224
- OpenAlex
- W2910751063
- Cited by
- 179
- References
- 7
- Citations by year
- 2026: 24 · 2025: 26 · 2024: 27 · 2023: 20 · 2022: 23 · 2021: 31 · 2020: 24 · 2019: 4
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01DK98414)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- acetaminophen overdose, hepatotoxicity, liver regeneration, acute liver failure, compensatory regeneration, growth factors, cytokines, angiogenic factors, mitogenic signaling, regenerative therapy
- MeSH terms
- Acetaminophen, Humans, Liver Regeneration, Liver Failure, Acute, Analgesics, Non-Narcotic, Chemical and Drug Induced Liver Injury, Drug Overdose
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