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Role of astrocytes and microglia in hepatic encephalopathy associated with advanced chronic liver disease:lessons from animal studies

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Neural Regeneration Research 2025年第12期20卷 3461-3475页

作者： Wouter Claeys Anja Geerts Lien Van Hoecke Christophe Van Steenkiste Roosmarijn E.Vandenbroucke Department of Internal Medicine and Paediatrics Hepatology Research UnitGhent UniversityGhentBelgium Liver Research Center Ghent Ghent UniversityGhent University HospitalGhentBelgium Barriers in Inflammation VIB-UGent Center for Inflammation ResearchVIBGhentBelgium Department of Biomedical Molecular Biology Ghent UniversityGhentBelgium Department of Gastroenterology and Hepatology Ghent University HospitalGhentBelgium Department of Gastroenterology and Hepatology Antwerp UniversityAntwerpBelgium Department of Gastroenterology and Hepatology Maria Middelares HospitalGhentBelgium

hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in *** clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of ***,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral *** circulating neurotoxins are ammonia and inflammatory *** the brain,pathophysiology is less well understood,but is thought to be driven by glial cell *** are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia *** on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative ***,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain *** evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system ***,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell ***-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic *** this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.

关键词： ammonia astrocytes cirrhosis hepatic encephalopathy microglia neuroinflammation osmotic stress oxidative stress systemic inflammation

Gut microbiome composition in patients with liver cirrhosis with and without hepatic encephalopathy: A systematic review and metaanalysis

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World Journal of Hepatology 2025年第1期17卷 96-111页

作者： Xiao-Tong Xu Min-Jie Jiang Yun-Lai Fu Fang Xie Jian-Jun Li Qing-Hua Meng Beijing Institute of Hepatology Beijing YouAn HospitalCapital Medical UniversityBeijing 100069China Interventional Therapy Center for Oncology Beijing YouAn HospitalCapital Medical UniversityBeijing 100069China Department of Infectious Diseases Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina

BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are *** To study the gut microbiota characteristics of patients with liver cirrhosis with and without *** We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut *** to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without *** data were analyzed using RevMan and *** Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic *** The gut microbiomes of patients with liver cirrhosis with and without HE *** gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.

关键词： Gut microbiome Cirrhosis hepatic encephalopathy Review Meta-analysis

hepatic encephalopathy: An Update on the Pathophysiology and Therapeutic Options

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Journal of Clinical and Translational Hepatology 2017年第2期5卷 142-151页

作者： Saleh Elwir Robert S.Rahimi Annette C.and Harold C.Simmons Transplant Institute Baylor University Medical Center Dallas TX USA

hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities,seen in patients with liver dysfunction and/or portosystemic *** of the most debilitating complications of cirrhosis,encephalopathy affects 30-45% of *** addition to significantly affecting the lives of patients and their caregivers,it is also associated with increased morbidity and mortality as well as significant utilization of health care *** this paper,we provide an overview on the pathophysiology,diagnosis,management and newer therapies of hepatic encephalopathy.

关键词： hepatic encephalopathy Cirrhosis Lactulose Rifaximin

The Gut Microbiota in hepatic encephalopathy:From Recognition to Treatment

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Journal of Clinical and Nursing Research 2025年第1期9卷 259-272页

作者： Chenghe Ding NHC Key Laboratory of Nuclear Technology Medical Transformation Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang 621000China

The role of the gut microbiota in the pathogenesis and treatment of hepatic encephalopathy (HE) has garnered increasing attention due to significant advancements in understanding the gut microbiota over recent years. A growing body of evidence from laboratory and clinical studies highlights a substantial relationship between gut microbiota and HE. Identifying the role of gut microbiota in maintaining normal cognitive function, including its influence on the gut barrier and immune cells, is essential to elucidate the mechanisms underlying the development of HE. This understanding offers novel perspectives for its prevention and treatment. This paper provides a comprehensive review of the research progress concerning the gut microbiota, HE, and their interrelationship, along with current treatment methods for HE. Furthermore, it outlines the limitations and challenges associated with microbiota-based therapeutic research.

关键词： Gut microbiota hepatic encephalopathy Gut barrier Treatment

hepatic encephalopathy before and neurological complications after liver transplantation have no impact on the employment status 1 year after transplantation

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World Journal of Hepatology 2017年第10期9卷 519-532页

作者： Henning Pflugrad Anita B Tryc Annemarie Goldbecker Christian P Strassburg Hannelore Barg-Hock Jürgen Klempnauer Karin Weissenborn Department of Neurology Hannover Medical School Integrated Research and Treatment Centre Transplantation Department of Gastroenterology Hepatology and EndocrinologyHannover Medical School Department of Medicine I University Hospital Bonn Clinic for Visceral and Transplant Surgery Hannover Medical School

To investigate the impact of hepatic encephalopathy before orthotopic liver transplantation (OLT) and neurological complications after OLT on employment after OLT. METHODSOne hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the PSE-Syndrome-Test yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), completed a questionnaire concerning their occupation and filled in the short form 36 (SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight (59.6%) patients were recruited before OLT, while on the waiting list for OLT at Hannover Medical School [age: 48.7 ± 10.2 years, 45 (66.2%) male], and 46 (40.4%) patients were included directly after OLT. RESULTSBefore OLT 43.0% of the patients were employed. The patients not employed before OLT were more often non-academics (employed: Academic/non-academic 16 (34.0%)/31 vs not employed 10 (17.6%)/52, P = 0.04), had more frequently a history of hepatic encephalopathy (HE) (yes/no; employed 15 (30.6%)/34 vs not employed 32 (49.2%)/33, P = 0.05) and achieved worse results in psychometric tests (RBANS sum score mean ± SD employed 472.1 ± 44.5 vs not employed 443.1 ± 56.7, P = 0.04) than those employed. Ten patients (18.2%), who were not employed before OLT, resumed work afterwards. The patients employed after OLT were younger [age median (range, min-max) employed 47 (42, 18-60) vs not employed 50 (31, 29-60), P = 0.01], achieved better results in the psychometric tests (RBANS sum score mean ± SD employed 490.7 ± 48.2 vs not employed 461.0 ± 54.5, P = 0.02) and had a higher health-related quality of life (SF 36 sum score mean ± SD employed 627.0 ± 138.1 vs not employed 433.7 ± 160.8; P < 0.001) compared to patients not employed after OLT.

关键词： hepatic encephalopathy Employment Neurological complications Cognitive function Health-related quality of life Liver transplantation

Covert hepatic encephalopathy: Agreement and predictive validity of different indices

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World Journal of Gastroenterology 2014年第42期20卷 15756-15762页

作者： Sara Montagnese Esmeralda Balistreri Sami Schiff Michele De Rui Paolo Angeli Giacomo Zanus Umberto Cillo Giancarlo Bombonato Massimo Bolognesi David Sacerdoti Angelo Gatta Carlo Merkel Piero Amodio Department of Medicine University of Padova Department of Surgical Oncological and Gastroenterological Sciences University of Padova

AIM: To investigate the agreement and prognostic value of different measures of covert hepatic encephalopathy (CHE).

关键词： hepatic encephalopathy Electroencephalography Psychometry Ammonia Liver cirrhosis

Clinical scenarios for the use of S100β as a marker of hepatic encephalopathy

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World Journal of Gastroenterology 2016年第17期22卷 4397-4402页

作者： Andrés Duarte-Rojo Astrid Ruiz-Margáin Ricardo U Macias-Rodriguez Francisco Javier Cubero José Estradas-Trujillo Rosa Ma Munoz-Fuentes Aldo Torre University of Arkansas for Medical Sciences Little Rock AR 72205 United States Department of Gastroenterology Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City 14000 Mexico Department of Internal Medicine III University Hospital RWTH Aachen 52074 Aachen Germany Department of Immunology Complutense University School of Medicine 28040 Madrid Spain

AIM: To evaluate the association between serum concentrations of S100β in patients with cirrhosis and the presence of low grade hepatic encephalopathy (HE).METHODS: This was a cross-sectional study. The population was categorized into four groups healthy subjects, cirrhosis without HE, cirrhosis with covert hepatic encephalopathy (CHE) and cirrhosis with overt HE. Kruskal-Wallis, Mann Whitney’s U with Bonferroni adjustment Spearman correlations and area under the ROC were used as ***: A total of 61 subjects were included, 46 cirrhotic patients and 15 healthy volunteers. S100β values were different among all groups, and differences remained significant between groups 1 and 2 (P hepatic encephalopathy score in patients with cirrhosis without HE compared to the patients with cirrhosis with CHE (r = -0.413, P = 0.019). ROC curve analysis yielded > 0.13 ng/mL as the best cutoff value of S100β for the diagnosis of HE (sensitivity 83.3%, specificity 63.6%).CONCLUSION: Serum concentrations of S100β are higher in patients with cirrhosis than in healthy volunteers, and are further increased in the presence of hepatic encephalopathy. The results suggest that serum biomarkers such as S100β could help in the correct characterization of incipient stages of HE.

关键词： hepatic encephalopathy S100β protein Astrocyte Psychometric hepatic encephalopathy score Critical flicker frequency

hepatic encephalopathy with status epileptics: A case report

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World Journal of Gastroenterology 2006年第11期12卷 1793-1794页

作者： Hiroto Tanaka Hiroki Ueda Yohei Kida Hiroko Hamagami Tomikimi Tsuji Masakazu Ichinose The Third Department of Internal Medicine Wakayama Medical University 811-1 KimiideraWakayama City641-0015Japan the Department of Neuropsychology Wakayama Medical University 811-1 KimiideraWakayama City641-0015Japan

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epileptic us. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy （phenytoin sodium） and treatment for hepatic encephalopathy （Branched chain amino acids）. The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

关键词： Status epilepticus hepatic encephalopathy Decompensated liver cirrhosis Electroencephalogram

Multimodality magnetic resonance imaging in hepatic encephalopathy: An update

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World Journal of Gastroenterology 2014年第32期20卷 11262-11272页

作者： Xiao-Dong Zhang Long-Jiang Zhang Sheng-Yong Wu Guang-Ming lu Department of Medical Imaging Jinling Hospital Nanjing Clinical School Southern Medical University Department of Medical Imaging Jinling Hospital Medical School of Nanjing University Department of Radiology Medical Imaging Institute of Tianjin

hepatic encephalopathy(HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging(MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight ofthe increasingly important role of blood oxygen level dependent functional MRI.

关键词： hepatic encephalopathy Magnetic resonance imaging Magnetic resonance spectroscopy Diffusion weighted imaging Default-mode network Blood oxygenation level dependent functional magnetic resonance imaging