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: 4 complete abstracts (792 words), 10 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
A syndrome characterized by central nervous system dysfunction in association with liver failure, including portal-systemic shunts. Clinical features include lethargy and confusion (frequently progressing to COMA); asterixis; nystagmus, pathologic; brisk oculovestibular reflexes; decorticate and decerebrate posturing; muscle spasticity; and bilateral extensor plantar reflexes (see reflex, babinski). electroencephalography may demonstrate triphasic waves. (From Adams et al., Principles of Neurology, 6th ed, pp1117-20; Plum and Posner, Diagnosis of Stupor and Coma, 3rd ed, p222-5)
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: Encephalopathies, Hepatic; Hepatic Encephalopathies; Portosystemic Encephalopathy; Encephalopathies, Portosystemic; Portosystemic Encephalopathies; Encephalopathy, Hepatic; Encephalopathy, Hepatocerebral; Encephalopathies, Hepatocerebral.
Where it fits in the MeSH classification
- Broader topics
- Liver Failure; Brain Diseases, Metabolic
Related concepts
- Liver Failure
- Confusion
- Asterixis
- Nystagmus
- Pathologic
- Muscle Spasticity
- Reflex
- Babinski
- Electroencephalography
Research landscape
PubMed indexes 11,960 records tagged with the MeSH heading “Hepatic Encephalopathy” (counts retrieved 2026-10-29). 1,603 of them (13.4%) were published from 2020 onward, and the busiest period so far is through 1999 with 6,438 records.
Reviews account for 2,040 records (17.1%) and meta-analyses for 163. Randomized controlled trials number 378 (3.2%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 6,438 |
| 2000-2009 | 1,606 |
| 2010-2019 | 2,313 |
| 2020 onward | 1,603 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,040 | 17.1% |
| Meta-analyses | 163 | 1.4% |
| Randomized controlled trials | 378 | 3.2% |
Method: PubMed query "Hepatic Encephalopathy"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in neuroscience
Neuroscience draws on tools with different strengths: cellular and animal work can manipulate circuits directly, while human imaging and electrophysiology observe the living brain at lower resolution. Small imaging studies are prone to false positives, and findings in animals do not always carry over to people. Clinical neurology and psychiatry rely on trials and cohort studies whose outcomes are often symptom scales. Check the species, the sample size, how the outcome was measured and whether results were replicated.
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 |
|---|---|---|---|---|
| The Link between Gut Microbiota and Hepatic Encephalopathy | 2022 | Review article Design not recorded in structured metadata | 48 | cc by PMID 36012266 · DOI · PMC9408988 |
| Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice | 2023 | Research article Design not recorded in structured metadata | 43 | cc by PMID 37488119 · DOI · PMC10366183 |
| A mouse model of hepatic encephalopathy: bile duct ligation induces brain ammonia overload, glial cell activation and neuroinflammation | 2022 | Research article Design not recorded in structured metadata | 36 | cc by PMID 36266427 · DOI · PMC9585018 |
| Development of overt hepatic encephalopathy increases mortality in patients with cirrhosis: a multicenter retrospective cohort study | 2026 | Research article Design not recorded in structured metadata | 3 | cc by PMID 41107663 · DOI · PMC12791057 |
The Link between Gut Microbiota and Hepatic Encephalopathy [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders.
- Closing excerpt
- We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy.
- 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 (203 words)
Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut-hepatic-brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36012266 · DOI · PMC9408988
Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Oxidative stress plays a crucial role in the pathogenesis of hepatic encephalopathy (HE), but the mechanism remains unclear.
- Closing excerpt
- These results define the key role of oxidative stress in the pathogenesis of HE.
- 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 (151 words)
Oxidative stress plays a crucial role in the pathogenesis of hepatic encephalopathy (HE), but the mechanism remains unclear. GABAergic neurons in substantia nigra pars reticulata (SNr) contribute to the motor deficit of HE. The present study aims to investigate the effects of oxidative stress on HE in male mice. The results validate the existence of oxidative stress in both liver and SNr across two murine models of HE induced by thioacetamide (TAA) and bile duct ligation (BDL). Systemic mitochondria-targeted antioxidative drug mitoquinone (Mito-Q) rescues mitochondrial dysfunction and oxidative injury in SNr, so as to restore the locomotor impairment in TAA and BDL mice. Furthermore, the GAD2-expressing SNr population (SNrGAD2) is activated by HE. Both overexpression of mitochondrial uncoupling protein 2 (UCP2) targeted to SNrGAD2 and SNrGAD2-targeted chemogenetic inhibition targeted to SNrGAD2 rescue mitochondrial dysfunction in TAA-induced HE. These results define the key role of oxidative stress in the pathogenesis of HE.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37488119 · DOI · PMC10366183
A mouse model of hepatic encephalopathy: bile duct ligation induces brain ammonia overload, glial cell activation and neuroinflammation [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Hepatic encephalopathy (HE) is a common complication of chronic liver disease, characterized by an altered mental state and hyperammonemia.
- Closing excerpt
- Additionally, this study further underscores the importance of neuroinflammation in the central effects of chronic liver disease.
- 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 (197 words)
Hepatic encephalopathy (HE) is a common complication of chronic liver disease, characterized by an altered mental state and hyperammonemia. Insight into the brain pathophysiology of HE is limited due to a paucity of well-characterized HE models beyond the rat bile duct ligation (BDL) model. Here, we assess the presence of HE characteristics in the mouse BDL model. We show that BDL in C57Bl/6j mice induces motor dysfunction, progressive liver fibrosis, liver function failure and hyperammonemia, all hallmarks of HE. Swiss mice however fail to replicate the same phenotype, underscoring the importance of careful strain selection. Next, in-depth characterisation of metabolic disturbances in the cerebrospinal fluid of BDL mice shows glutamine accumulation and transient decreases in taurine and choline, indicative of brain ammonia overload. Moreover, mouse BDL induces glial cell dysfunction, namely microglial morphological changes with neuroinflammation and astrocyte reactivity with blood-brain barrier (BBB) disruption. Finally, we identify putative novel mechanisms involved in central HE pathophysiology, like bile acid accumulation and tryptophan-kynurenine pathway alterations. Our study provides the first comprehensive evaluation of a mouse model of HE in chronic liver disease. Additionally, this study further underscores the importance of neuroinflammation in the central effects of chronic liver disease.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36266427 · DOI · PMC9585018
Development of overt hepatic encephalopathy increases mortality in patients with cirrhosis: a multicenter retrospective cohort study [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundOvert hepatic encephalopathy (OHE) is a severe complication of liver cirrhosis.
- Closing excerpt
- Therefore, close monitoring of high-risk populations is warranted for early management of OHE.
- 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 (241 words)
BackgroundOvert hepatic encephalopathy (OHE) is a severe complication of liver cirrhosis. However, data on its incidence, prognostic significance, and associated risk factors in patients without OHE at baseline remain limited.MethodsA multicenter retrospective cohort study was conducted by reviewing records of hospitalized patients with cirrhosis at three institutions in Japan. OHE was defined as West Haven grade ≥ 2 and its incidence during the follow-up was estimated using the cumulative incidence function. Prognostic factors were assessed using Cox proportional hazards regression analysis, with OHE and hepatocellular carcinoma (HCC) development treated as time-dependent covariates. Independent predictors for OHE development were analyzed using fine-gray proportional hazards regression analysis.ResultsAmong 652 patients, the median age was 67 years, and 53% were male. The median model for end-stage liver disease (MELD) score was 9. During a median follow-up period of 3.2 years, 136 patients (21%) developed OHE and 183 patients (28%) died. The cumulative incidence of OHE at 1, 3, and 5 years was 8%, 16%, and 20%, respectively. Multivariable analysis demonstrated that OHE development (hazard ratio [HR], 3.07; 95% confidence interval [CI], 1.99-4.75) was a significant independent prognostic factor, regardless of age, sex, liver functional reserve, and HCC development. Furthermore, multivariable analysis identified lower body mass index, higher MELD score, lower albumin levels, and higher ammonia levels as independent predictors for OHE development.ConclusionsOHE development is common and increases mortality among patients with cirrhosis. Therefore, close monitoring of high-risk populations is warranted for early management of OHE.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41107663 · DOI · PMC12791057
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 Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver [5]
- Research article The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis [6]
- Research article Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy [7]
- Research article Hepatic Encephalopathy [8]
- Research article EASL Clinical Practice Guidelines on the management of hepatic encephalopathy [9]
- Research article Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic Principles [10]
References
- Won SM, Oh KK, Gupta H, Ganesan R, Sharma SP, Jeong JJ, et al.. The Link between Gut Microbiota and Hepatic Encephalopathy. . 2022. PMID 36012266 · DOI · PMC9408988
- Bai Y, Li K, Li X, Chen X, Zheng J, Wu F, et al.. Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice. . 2023. PMID 37488119 · DOI · PMC10366183
- Claeys W, Van Hoecke L, Geerts A, Van Vlierberghe H, Lefere S, Van Imschoot G, et al.. A mouse model of hepatic encephalopathy: bile duct ligation induces brain ammonia overload, glial cell activation and neuroinflammation. . 2022. PMID 36266427 · DOI · PMC9585018
- Iwasa T, Miwa T, Utakata Y, Oi M, Asakura M, Onishi T, et al.. Development of overt hepatic encephalopathy increases mortality in patients with cirrhosis: a multicenter retrospective cohort study. . 2026. PMID 41107663 · DOI · PMC12791057
- Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al.. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014. PMID 25042402 · DOI
- Arroyo V, Angeli P, Moreau R, Jalan R, Clària J, Trebicka J, et al.. The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis. J Hepatol. 2021. PMID 33301825 · DOI
- Rose CF, Amodio P, Bajaj JS, Dhiman RK, Montagnese S, Taylor-Robinson SD, et al.. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol. 2020. PMID 33097308 · DOI
- Wijdicks EF. Hepatic Encephalopathy. N Engl J Med. 2016. PMID 27783916 · DOI
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022. PMID 35724930 · DOI
- Weissenborn K. Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic Principles. Drugs. 2019. PMID 30706420 · DOI · PMC6416238
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 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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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.