Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (678 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Hepatic Failure.
Where it fits in the MeSH classification
- Broader topics
- Hepatic Insufficiency
- Narrower topics
- End Stage Liver Disease; Hepatic Encephalopathy; Liver Failure, Acute
Related concepts
- Liver
- Jaundice
- Ammonia
- Bilirubin
- Alkaline Phosphatase
- Aspartate Aminotransferase
- Lactate Dehydrogenases
Research landscape
PubMed indexes 32,836 records tagged with the MeSH heading “Liver Failure” (counts retrieved 2026-11-04). 7,420 of them (22.6%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 10,835 records.
Reviews account for 5,414 records (16.5%) and meta-analyses for 343. Randomized controlled trials number 633 (1.9%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 7,940 |
| 2000-2009 | 6,641 |
| 2010-2019 | 10,835 |
| 2020 onward | 7,420 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 5,414 | 16.5% |
| Meta-analyses | 343 | 1.0% |
| Randomized controlled trials | 633 | 1.9% |
Method: PubMed query "Liver Failure"[MeSH Terms] with publication-type and date filters, retrieved 2026-11-04.
Reading the evidence in digestive system and liver
Gut and liver research ranges from laboratory studies of the microbiome to large trials of drugs and surgery. Symptoms such as pain, reflux or bowel change are reported by patients and overlap between conditions, and diet and microbiome studies are mostly observational. Check whether the study measured symptoms, tissue findings or long-term outcomes, how the diagnosis was made and how long people were followed. Nothing here replaces advice from a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Reversal of ACLF and ALF using whole blood extracorporeal system combining HLA-depleted liver organoids with granulocyte-monocyte apheresis | 2026 | Research article Design not recorded in structured metadata | 11 | cc by PMID 41044028 · DOI · PMC12765605 |
| Panose prevents acute-on-chronic liver failure by reducing bacterial infection in mice | 2025 | Research article Design not recorded in structured metadata | 7 | cc by PMID 40478727 · DOI · PMC12259250 |
| Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway | 2026 | Research article Design not recorded in structured metadata | 6 | cc by PMID 41340222 · DOI · PMC12866713 |
Reversal of ACLF and ALF using whole blood extracorporeal system combining HLA-depleted liver organoids with granulocyte-monocyte apheresis [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Background & aimsAcute-on-chronic liver failure (ACLF) is characterized by catastrophic loss of liver function in patients with advanced chronic liver disease, with 28-day mortality rates reaching up to 80%.
- Closing excerpt
- This therapy could offer an off-the-shelf treatment option for patients with life-threatening liver failure.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (318 words)
Background & aimsAcute-on-chronic liver failure (ACLF) is characterized by catastrophic loss of liver function in patients with advanced chronic liver disease, with 28-day mortality rates reaching up to 80%. Despite advances in intensive care, the high mortality primarily stems from the absence of a therapeutic modality that simultaneously addresses both the profound systemic inflammatory response and severe hepatic synthetic dysfunction.MethodsWe designed an integrated extracorporeal circuit, termed the UTOpiA system, which combines granulocyte and monocyte apheresis (GMA) with human induced pluripotent stem cell-derived hepatocyte-like cell (iHLC) organoids engineered with HLA-A, HLA-B, and CIITA triple knockout. The efficacy of UTOpiA was tested after direct whole blood exposure through venous flow in rat models of ACLF and acute liver failure (ALF).ResultsUTOpiA treatment significantly improved survival in both ACLF and ALF rat models, outperforming GMA or iHLC monotherapy and HepG2 cell-based devices. Improved survival was associated with reduced coma severity, improved liver biochemistry, and reduced hyperammonaemia, hyperbilirubinemia, and systemic inflammation. Transcriptomic and histological analyses revealed restoration of hepatic metabolic gene expression and hepatocyte regeneration. Mechanistically, iHLC-secreted α-fetoprotein suppressed hepatocyte cell cycle arrest via p21 downregulation and enhanced regeneration, while UTOpiA restored HNF4α activity and dampened pro-inflammatory cytokines, including IL-6 and TNF-α.ConclusionsThe tandem UTOpiA circuit confers a significant survival benefit in preclinical rodent models of ACLF and ALF by providing anti-inflammatory, synthetic, and metabolic support. Elucidating the regenerative signals that promote recovery of the injured liver may further expand the potential of this whole blood extracorporeal system as a novel, off-the-shelf liver support therapy.Impact and implicationsRestoring hepatic metabolism while controlling inflammation in acutely decompensated cirrhosis remains a major unmet clinical need. By combining HLA-modified human induced pluripotent stem cell-derived liver organoids with granulocyte and monocyte apheresis, we developed a bioartificial liver system that manages inflammation, restores liver function, and promotes regeneration in two rat models of severe liver failure. This therapy could offer an off-the-shelf treatment option for patients with life-threatening liver failure.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41044028 · DOI · PMC12765605
Panose prevents acute-on-chronic liver failure by reducing bacterial infection in mice [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Acute-on-chronic liver failure (ACLF) is a leading cause of global liver-related mortality.
- Closing excerpt
- These findings highlight panose's potential in preventing bacterial infection, offering a valuable insight into mitigating ACLF progression.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (170 words)
Acute-on-chronic liver failure (ACLF) is a leading cause of global liver-related mortality. Bacterial infection, especially in patients with decompensated cirrhosis, commonly triggers ACLF and is difficult to treat with antibiotics. Therefore, finding alternative strategies for preventing and managing bacterial infection is an urgent priority. Here, we observed that patients with bacterial infection and decompensated cirrhosis, as well as ACLF mice, exhibited lower fecal panose levels than uninfected controls. Megamonas funiformis, with 4α-glucanosyltransferase (4αGT) as a key enzyme for panose production, was identified as a potential panose producer. Animal experiments demonstrated that panose efficiently reduced liver injury and extended survival in ACLF mice by mitigating bacterial infection. Further results revealed that panose enhanced resistance to bacterial infection by inhibiting oxidative stress-induced gut barrier disruption, thereby limiting bacterial dissemination. Mechanistically, panose interacted with the solute carrier family 7 member 11 (SLC7A11, also known as xCT) protein to boost antioxidant glutathione levels in intestinal epithelial cells. These findings highlight panose's potential in preventing bacterial infection, offering a valuable insight into mitigating ACLF progression.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40478727 · DOI · PMC12259250
Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Acute liver failure (ALF) is a life-threatening, multifactorial condition characterized by rapid progression, extensive hepatocellular necrosis, and high mortality rates.
- Closing excerpt
- These findings suggest that PC-Ca represents a promising therapeutic strategy for ALF, with the modulation of mitochondrial homeostasis offering valuable insights for the development of next-generation pharmacological interventions.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (190 words)
Acute liver failure (ALF) is a life-threatening, multifactorial condition characterized by rapid progression, extensive hepatocellular necrosis, and high mortality rates. Current therapeutic options, including artificial liver support systems (ALSS) and liver transplantation, are limited by high costs, donor shortages, and insufficient efficacy. Mitochondrial dysfunction and necrotic cell death play central roles in both acute and chronic liver injury; however, their contribution to ALF remains poorly understood. In this study, self-assembled procyanidin capsules (PC-Ca) are developed with sustained antioxidant and anti-inflammatory properties that selectively accumulate in the liver of an ALF model. These findings demonstrate that PC-Ca significantly improves survival rates and more effectively mitigates liver injury, inflammation, and necrosis in thioacetamide (TAA)-induced ALF in mice and rabbits than the standard clinical agent, N-acetylcysteine (NAC). This protective effect is mediated through enhanced oxidative stress defense via activation of the KEAP1-NRF2 axis and inhibition of necroptosis via the RIPK1/RIPK3/MLKL pathway. In addition, PC-Ca preserves mitochondrial morphology and function via the PGAM5/DRP1/PINK1 pathway, offering hepatoprotection. These findings suggest that PC-Ca represents a promising therapeutic strategy for ALF, with the modulation of mitochondrial homeostasis offering valuable insights for the development of next-generation pharmacological interventions.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41340222 · DOI · PMC12866713
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Symptom prevalence and quality of life of patients with end-stage liver disease: A systematic review and meta-analysis [4]
- Research article Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis [5]
- Research article Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy [6]
- Research article Systematic review: glucocorticosteroids for alcoholic hepatitis--a Cochrane Hepato-Biliary Group systematic review with meta-analyses and trial sequential analyses of randomized clinical trials [7]
- Research article Pregnancy outcomes of liver transplant recipients: a systematic review and meta-analysis [8]
- Research article Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis [9]
References
- Yamaguchi H, Yoneyama Y, Ichimura K, Ohtsu K, Soen M, Moriya C, et al.. Reversal of ACLF and ALF using whole blood extracorporeal system combining HLA-depleted liver organoids with granulocyte-monocyte apheresis. . 2026. PMID 41044028 · DOI · PMC12765605
- Li J, Xie S, Chen M, Hong C, Chen Y, Lyu F, et al.. Panose prevents acute-on-chronic liver failure by reducing bacterial infection in mice. . 2025. PMID 40478727 · DOI · PMC12259250
- Shi Q, Wu M, Zhong J, Chen C, Huang Z, Peng J, et al.. Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway. . 2026. PMID 41340222 · DOI · PMC12866713
- Peng JK, Hepgul N, Higginson IJ, Gao W. Symptom prevalence and quality of life of patients with end-stage liver disease: A systematic review and meta-analysis. Palliat Med. 2019. PMID 30345878 · DOI · PMC6291907
- Mezzano G, Juanola A, Cardenas A, Mezey E, Hamilton JP, Pose E, et al.. Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis. Gut. 2022. PMID 33436495 · DOI
- Kimer N, Krag A, Møller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014. PMID 24849268 · DOI
- Rambaldi A, Saconato HH, Christensen E, Thorlund K, Wetterslev J, Gluud C. Systematic review: glucocorticosteroids for alcoholic hepatitis--a Cochrane Hepato-Biliary Group systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Aliment Pharmacol Ther. 2008. PMID 18363896 · DOI
- Deshpande NA, James NT, Kucirka LM, Boyarsky BJ, Garonzik-Wang JM, Cameron AM, et al.. Pregnancy outcomes of liver transplant recipients: a systematic review and meta-analysis. Liver Transpl. 2012. PMID 22344967 · DOI
- McPhail MJ, Farne H, Senvar N, Wendon JA, Bernal W. Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis. Clin Gastroenterol Hepatol. 2016. PMID 26499930 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.