Chronic Hepatic Encephalopathy Research Articles

Short Working Memory Impairment Associated with Hippocampal Microglia Activation in Chronic Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a major neuropsychological condition that occursas a result of impaired liver function. It is frequently observed in patients with advanced liver disease or cirrhosis. Memory impairment is among the symptoms of HE; the pathophysiologic mechanism for this enervating condition remains unclear. However, it is possible that neuroinflammation may be involved, as recent studies have emphasized such phenomena. Therefore, the aim of the present study is to assess short working memory (SWM) and examine the involvement of microglia in a chronic model of HE. The study was carried out with male Wistar rats that were induced by repeated thioacetamide (TAA) administration (100 mg/kg i.p injection for 10 days). SWM function was assessed through Y-maze, T-Maze, and novel object recognition (NOR) tests, together with an immunofluorescence study of microglia activation within the hippocampal areas. Our data showed impaired SWM in TAA-treated rats that was associated with microglial activation in the three hippocampal regions, and which contributed to cognitive impairment.

Nutraceuticals rich in zinc and branched chain amino acids for improving quality of life in patients with chronic liver disease, hepatic encephalopathy, and geriatrics

The current paper aimed to highlight the role of nutraceuticals rich in zinc and branched chain amino acids (BCAAs) for improving the quality of life (QoL) in patients with chronic liver disease (CLD), hepatic encephalopathy (HE), and geriatrics. Well-done works based on evidence-based approach were studied thoroughly in order to define the CLD and HE and extract an informative and concise report with valuable knowledge about the important role of zinc and BCAAs as an adjuvant nutraceutical therapy included in the treatment protocol of the CLD and HE, with many health benefits for geriatrics health. Novel nutraceutical formulations structured on scientific basis according to official guidelines were outlined as beneficial dietary supplements containing whey protein as a functional food of milk derivatives with proven health benefits and valuable content (18%) of BCAAs, fortified with a bunch of vitamins, minerals, steviol glycosides (SGs) and natural flavors. It could be concluded the valuable role of zinc and BCAAs in improving QoL in patients with CLD, HE, and geriatrics.

Opsoclonus in Alcohol Withdrawal Syndrome with Chronic Liver Disease and Hepatic Encephalopathy

Opsoclonus in Alcohol Withdrawal Syndrome with Chronic Liver Disease and Hepatic Encephalopathy

Neurometabolism and brain morphometry in an adolescent female with an extra-hepatic congenital portosystemic shunt.

Chronic hepatic encephalopathy (CHE) has been reported both in patients with congenital porto-systemic shunts (CPSS) and chronic liver disease. CHE is difficult to recognize in children as there is no clear definition and its manifestations are highly variable. CHE is associated with variations in brain volumes and metabolites that have already been demonstrated using 1.5-3T MRI systems. However, the in-depth study of brain metabolism requires the high spectral resolution of high magnetic fields. We analyzed the neurometabolic profile, brain volumes and T1 relaxation times of a child with a CPSS using high field proton magnetic resonance spectroscopy (1H MRS, 7T) combined with MRI and compared it to an age-matched control group. We also evaluated the impact of shunt closure on neurocognitive symptoms using adapted neuropsychological tests. 7T MRS revealed a significant increase in glutamine compared to controls, a decrease in brain osmolytes, and a slight elevation in NAA concentrations. 7T MRI scans showed morphological abnormalities but no changes in the signal intensity of the globus pallidus. Neurocognitive testing revealed attention deficit disorder, language difficulties, and mild intellectual disability. Most of these areas improved after shunt closure. In this paediatric case of type B HE with normal fasting ammonia, neurometabolic profile was compatible with what has been previously shown in chronic liver disease, while also demonstrating an isolated glutamine peak. In addition, neurocognitive function partially improved after shunt closure, arguing strongly for shunt closure in both presymptomatic and symptomatic patients.

Parkinson’s mimicker in Acute and Chronic Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a neuropsychiatric spectrum mainly caused by cirrhosis, portosystemic shunt, or portal hypertension. It may also mimic the presentation of Parkinson’s disease, which can make clinical diagnosis a challenge. A 42-year-old man with underlying chronic hepatitis C with liver cirrhosis was initially admitted for chronic lower back pain. During admission, he appeared drowsy but was able to answer questions appropriately albeit with delayed and slow speech. He had bradykinesia without stigmata of chronic liver disease. Differentials at the time were hypoactive delirium and Parkinson’s disease. Blood results were normal. Magnetic resonance imaging (MRI) of the brain showed bilateral symmetrical hyperintensities at the inferior temporal lobes, medial thalamus, cingulate gyri, head of caudate nuclei, posterior limbs of internal capsules and insula on fluid-attenuated inversion recovery (FLAIR) sequence. On the T1 weighted imaging (T1WI) sequence, bilateral symmetrical hyperintensities were seen at globus pallidi, cerebral peduncles and periaqueductal regions extending to superior cerebellar peduncles. Based on imaging, a diagnosis of acute chronic hepatic encephalopathy was made. The patient was treated conservatively in the ward and was discharged with persistent Parkinsonism. In patients with neurological abnormalities where hepatic encephalopathy (HE) is least expected due to subtle symptoms, MRI could play an important role in eliciting the underlying cause, and extent of disease and for prognostication.

Interventional Radiology Management of Advanced Schistosomiasis: State of the Art

AbstractAdvanced schistosomiasis is an infectious disease, endemic in some regions, with long-term implications for patient care. It can be associated with conditions such as portal hypertension, variceal hemorrhage, chronic hepatic encephalopathy, and hepatocellular carcinoma. In this article, an overview of the most recent data about the role of interventional radiology in the management of these conditions will be presented, as well as the authors' experience on interventional management of schistosomiasis patients.

P17 The Beneficial Effect of Oral Cr Supplementation in an Early Childhood Rat Model of Chronic Hepatic Encephalopathy: In Vivo Longitudinal 1H and 31P Magnetic Resonance Spectroscopy Study

P17 The Beneficial Effect of Oral Cr Supplementation in an Early Childhood Rat Model of Chronic Hepatic Encephalopathy: In Vivo Longitudinal 1H and 31P Magnetic Resonance Spectroscopy Study

P8 Cognitive Impairment Associated With Cortical and Hippocampal Microglia Activation and Altered Synaptic Function in a Rat Model of Chronic Hepatic Encephalopathy

P8 Cognitive Impairment Associated With Cortical and Hippocampal Microglia Activation and Altered Synaptic Function in a Rat Model of Chronic Hepatic Encephalopathy

Development and validation of a dynamic online nomogram for predicting acute kidney injury in cirrhotic patients upon ICU admission.

Acute kidney injury (AKI) is one of the most common and deadly complications among cirrhotic patients at intensive care unit (ICU) admission. We aimed to develop and validate a simple and clinically useful dynamic nomogram for predicting AKI in cirrhotic patients upon ICU admission. We analyzed the admission data of 4,375 patients with liver cirrhosis in ICU from 2008 to 2019 in the intensive care unit IV (MIMIC-IV) database. The eligible cirrhotic patients were non-randomly divided into derivation (n = 2,188) and validation (n = 2,187) cohorts at a ratio of 1:1, according to the order of admission. The least absolute shrinkage and selection operator regression model was used to identify independent predictors of AKI in the derivation cohort. A dynamic online nomogram was built using multivariate logistic regression analysis in the derivation cohort and then validated in the validation cohort. The C-index, calibration curve, and decision curve analysis were used to assess the nomogram's discrimination, calibration, and clinical usefulness, respectively. The incidence of AKI in 4,375 patients was 71.3%. Ascites, chronic kidney disease, shock, sepsis, diuretic drugs, hepatic encephalopathy, bacterial infections, vasoactive drugs, admission age, total bilirubin, and blood urea nitrogen were identified using the multivariate logistic regression analysis as significant predictors of AKI upon ICU admission. In the derivation cohort, the model showed good discrimination (C-index, 0.786; 95% CI, 0.765-0.806) and good calibration. The model in the validation cohort yielded good discrimination (C-index, 0.774; 95% CI, 0.753-0.795) and good calibration. Decision curve analysis demonstrated that the dynamic online nomogram was clinically useful. Our study presents a dynamic online nomogram that incorporates clinical predictors and can be conveniently used to facilitate the individualized prediction of AKI in cirrhotic patients upon ICU admission.

Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study

The aim of the study – determining the immunohistochemical levels of the GFAP, GS and AQP4 in different regions of the human brain in the conditions of liver cirrhosis of different degree. Materials and methods. The study was performed on sectional material of 90 patients who suffered during lifetime from liver non-alcoholic cirrhosis of classes A (n = 30, group “A”), B (n = 30, group “B”) and C (n = 30, group “C”) according to Child–Pugh classification, including 59 (65.55 %) cases with clinical symptoms of I–IV grade hepatic encephalopathy. Cortex, white matter, hippocampus, thalamus, striopallidum, cerebellum, were examined using immunohistochemical method for evaluation of GFAP, GS and AQP4 levels. Results. GFAP expression gradually decreased from classes A to C of cirrhosis. The most expressed GFAP decline was found in class C in the cortex and thalamus (6.74- and 6.23-fold decrease). Contrary to GFAP, GS expression gradually increased along with aggravation of cirrhosis. The most prominent augmentation of GS was related in the cortex and thalamus in “C” group, respectively 4.34- and 4.26-fold increase. AQP4 levels also showed growing mode correlated with cirrhosis aggravation. The highest increase was found in the cortex and thalamus in “C” group (4.25- and 4.34-fold increase, respectively). Starting from class B, altered GFAP, GS, and AQP4 levels showed region-dependent relationships. GS and AQP4 were positively correlated in all 6 studied regions, while the inverse relationships were found between GFAP vs. GS and GFAP vs. AQP4 proteins. Conclusions. As early as in class A of cirrhosis, dynamic molecular alterations are occurred in the brain astrocytes, indicating the progressive development of astroglial remodeling with a violation of its cytoskeleton and redistribution of molecular domains within cells. This phenomenon is region- and time-specific; its signs get stronger with time from class to class, becoming most pronounced in class C. Among studied brain regions, cortex and thalamus are characterized by the most pronounced protein changes. Starting from class B, the remarkable relationship is seen between molecular changes of both direct and inverse type. Simultaneously emerging links might indicate synergistic involvement of these molecules in astroglial remodeling in chronic hepatic encephalopathy. Alterations in the mentioned astroglial molecular complex can serve both as a diagnostic marker of reactive astrogliosis during liver cirrhosis and represent a target for novel therapeutic approaches regarding encephalopathy in cirrhotic patients.

The potential role of lactulose pharmacotherapy in the treatment and prevention of diabetes.

The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Bifidobacterium as well as suppress the potentially pathogenic bacteria Escherichia coli. These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes via actions on the gut microbiota.

Transjugular intrahepatic portosystemic shunt for portal hypertension: 30 years experience from China.

Liver diseases are a major cause of illness and death worldwide. In China, liver diseases, primarily viral hepatitis, affect approximately 300 million people, thus having a major impact on the global burden of liver diseases. Portal hypertension is the most severe complication of chronic liver diseases, including ascites, hepatic encephalopathy and bleeding from gastroesophageal varices. Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of these complications. Since its introduction 30 years ago in China, the use of TIPS has evolved and has played an increasingly important role in the management of the complications of portal hypertension. This review will focus on the history, current application and management of complications of TIPS in China.

Protective effect of probiotics and ascorbic acid on bile duct ligation-induced chronic hepatic encephalopathy in rats.

Background and purpose:Hepatic encephalopathy (HE) is a brain dysfunction caused by acute and chronic hepatic failure. The pathogenesis of HE is unknown, although small intestinal bacterial overgrowth associated with chronic liver damage, hyperammonemia, and oxidative stress are considered major factors for HE. Effective lowering of circulating ammonia and neuroinflammation is the main strategy for preventing and treating HE in cirrhosis. In the present study, the protective effect of probiotics (Lactobacillus plantarum and Bacillus clausii) and ascorbic acid in combination was assessed in bile duct ligation (BDL)-induced chronic HE in rats.Experimental approach:Sprague Dawley rats were divided into five groups (n = 6). All groups were subjected to double ligation of the bile duct and fed a hyperammonemia diet, except group I (normal control). Groups III and IV were treated with a low and high dose of combination therapy, respectively, while group V was given lactulose. Four weeks post ligation, behavioral, biochemical, and neurochemical parameters were measured. The liver and brain were dissected for histopathology and protein analyses.Findings / Results:Combination therapy reduced plasma AST, ALT, ALP, and ammonia levels and attenuated hepatic inflammation/fibrosis in cirrhotic rats. Furthermore, combination therapy significantly improved behavioral parameters and restored the antioxidant enzyme activity. Histological changes were observed in the brain and liver of BDL animals.Conclusion and implications:The additive impact of probiotics and ascorbic acid on BDL-induced chronic HE in rats was mediated by a reduction in ammonia and oxidative stress, implying the therapeutic potential of combination therapy in HE.

A Study to Assess Prevalence and Drug Utilization Pattern in Hepatic Impairment Patients with or without Comorbidities in a Tertiary Care Teaching Hospital

<p style="text-align: justify;"><strong>Background: </strong>The liver is the core of metabolic activity in the body. Around 50% of the classes of drugs are known to be hepatotoxic. Thus prescribing medications in patients with liver disease is indeed a challenging task.<strong> Objectives:</strong> To study the prevalence and to carry out the drug utilization evaluation of the therapy prescribed among hepatic impairment patients. <strong>Methodology:</strong> A prospective observational study was carried out for six months among inpatients of the medicine department of Chigateri district hospital. Patients were enrolled on the basis of inclusion criteria; data was collected using a data collection form and results were analyzed using MS Excel. <strong>Results: </strong>A total of 160 patients were enrolled, the most prevalent condition was alcoholic liver disease (<em>n</em>=66, 41.25%) followed by chronic liver disease (<em>n</em>=47, 29.38%) and hepatic encephalopathy (<em>n</em>=12, 7.5%). Out of 1466 drugs been prescribed, 795 drugs were used specifically for hepatic impairment. Drugs used to treat oedema (diuretics) were most commonly prescribed (<em>n</em>=198, 25%) followed by gall stone dissolution agents (<em>n</em>=124, 16%) and sugars (<em>n</em>=97, 12%). <strong>Conclusion: </strong>Alcoholic liver disease was the most prevalent hepatic condition, followed by chronic liver disease. The diuretics were the most widely used hepato-specific drugs among the patients. <p style="text-align: justify;"><strong>Key words:</strong> Drug utilization pattern, Hepatic impairment, Abstinence, Diuretics.

English

Major sources of the vascular supply of the gastrointestinal tract are the celiac trunk (CT) and superior mesenteric artery (SMA) which are the main proximal branches of the abdominal aorta. The CT gives rise to three branches normally as follows: left gastric artery (LGA), common hepatic artery (CHA) and splenic artery (SA). The branching pattern of the CT is considered as the most literature explained anatomical pattern.1 After the CT, the abdominal aorta gives the second named branch as superior mesenteric artery. Vascular variations of the celiac trunk and superior mesenteric artery are common and had been described earlier.2 These variations are caused due to the aberrant embryological development of splanchnic arteries. The incidence of hepato-spleno-mesenteric trunk has been reported by various authors as 0.68 %,3 0.7 %,4 0.3 %,5 0.4 %,6 or 1 %.7 The importance of knowledge of these variations lies in preplanning of invasive surgical techniques, organ transplantation, diagnosis, prevention, and management of some metastatic tumours and to overcome the catastrophic consequences like bowel ischemia due to common trunk.8 Hence a better understanding of these anatomical variations is considered vital for surgeons or radiologists for appropriate planning and conduction of surgical procedures or interventions.9 Most of the anatomical variations in abdominal aorta branches are asymptomatic and incidental findings while imaging for other aetiologies. But the identification of such vascular variations is of utmost importance in clinical practice. The Hepatospleno-mesenteric trunk [HSMT] is one of those variations and was less frequently reported. The authors describe a case report of the hepato-spleno-mesenteric trunk which was incidentally detected in the multi detector computed tomography study of the abdomen of a 54-year-old male patient who had been diagnosed to have chronic liver disease and hepatic encephalopathy. The origin of the HSMT [with a diameter of 11mm] occurs from the abdominal aorta at the level of the L2 vertebral body and is divided into the hepatosplenic trunk [diameter of 7 mm] and superior mesenteric artery [diameter of 7.5 mm] after coursing for a length of 28 mm. The hepatosplenic trunk ascends superiorly for a length of 20 mm and divided into two terminal branches: common hepatic (6 mm) and splenic artery (6 mm).

Comparative Evaluation of Neuropathological Lesions Progression in Different Brain Areas in A Rat Model of Chronic Hepatic Encephalopathy

Hepatic encephalopathy (HE) is considered a serious clinical complication of acute and chronic liver injury. Previous researches elucidated HE but the characterization of neuropathology in different brain areas is limited. The present study is conducted to evaluate the progression of neuropathological lesions in different brain areas in a rat model with liver fibrosis induced by thioacetamide (TAA). For this experiment, 20 male rats were divided into two groups control and TAA-treated group that was I.P injected twice a week with 100 mg/kg.b.w TAA dissolved in saline for 3 months. Three rats from each group were euthanized after 3 months and the liver specimens were collected for ensuring the development of a rat model for liver fibrosis. The remained rats were kept without further treatment with TAA for 2 months, rats were carefully monitored for abnormal signs. After the end of the experimental period, rats were euthanized and the brains were collected for histopathological examination. Microscopic examination of the brain revealed various neuropathological lesions that varied in severity between different brain areas. The most severe lesions were recorded in the midbrain and pons while mild lesions were detected in the cerebral cortex and striatum. The brain lesions comprised varied degrees of neuronal degeneration with marked astroglial and microglial reactions in the different brain regions. The obvious inflammatory reaction indicates that neuroinflammation plays an important role in the mediation of HE.

Comparative Evaluation of Neuropathological Lesions Progression in Different Brain Areas in A Rat Model of Chronic Hepatic Encephalopathy

Comparative Evaluation of Neuropathological Lesions Progression in Different Brain Areas in A Rat Model of Chronic Hepatic Encephalopathy

Embolization of a paraumbilical shunt by the transparaumbilical venous approach and one-sheath inverse method: A case report

We describe treatment of a 53-year-old man with chronic hepatic encephalopathy. Contrast-enhanced computed tomography demonstrated a recanalized paraumbilical vein as a portosystemic shunt connecting the left branch of the portal vein and bilateral iliac veins. Percutaneous embolization was performed. The paraumbilical vein was punctured under ultrasonographic guidance; a 7-Fr sheath was inserted in the cranial direction. The hepatic side of the shunt was embolized with a vascular plug. The sheath direction was inverted to the caudal side; the pelvic side of the shunt was then embolized with another vascular plug. This report demonstrates that the percutaneous transparaumbilical venous approach is useful and safe for portosystemic shunt intervention. Moreover, the one-sheath inverse method was useful for embolization of upstream and downstream sides of the puncture site.

P: 78 Mechanism of Alzheimer Type II Astrocyte Development: Implication for the Defective Neuronal Integrity and Neurobehavioral Deficits Associated With Chronic Hepatic Encephalopathy

BACKGROUND: Chronic hepatic encephalopathy (CHE) is a major neurological condition that occurs following chronic liver failure (CLF) following drug-induced hepatotoxicity, viral hepatitis, or exposure to various hepatotoxins. CHE is characterized by mental confusion, behavioral changes, and motor disturbances. The molecular basis for CHE remains elusive. The presence of Alzheimer type II astrocytes (AT2A) is the only histopathological findings observed in CHE. However, little is currently known regarding its development, and its involvement in the pathogenesis of CHE. METHODS: Astrocytic glia maturation factor and other inflammatory factors were measured by western blots, immunohistochemistry, and by ELISA. AT2A was analyzed by histopathology. RESULTS: We identified increased levels of astrocytc glia maturation factor (GMF), a factor strongly implicated in neuroinflammation and in the overexpression of various inflammatory factors (IL-1β, TNF-α, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), matrix metalloproteinase-3 (MMP-3), prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2), as well as reduced levels of α-tubulin and glial fibrillary acidic protein, along with increased levels of aggregated nuclear protein lamin a/c in the thioacetamide-induced rat model of CHE. Further, we identified reduced levels of neuronal proteins, PSD95, synaptophysin, and NMDA-nr1. Moreover, synaptic density and dendritic complexity are reduced post-CLF. Since elevated blood/brain ammonia levels have been strongly implicated in the pathogenesis of CHE, while exposure of cultured astrocytes to ammonia was shown to develop AT2A, we utilized this in vitro system to delineate mechanisms by which ammonia contributes to the development of AT2A. We found increased levels of GMF, aggregated nuclear protein lamin a/c, and inflammatory factors (IL-1β, TNF-α, IL-6, CXCL1, MMP-3, PGE2 and COX2), as well as reduced levels and oxidized forms of α-tubulin in astrocytes post-ammonia treatment, which was similar to that found in vivo. Further, exposure of cultured neurons to conditioned media (CM) from ammonia-treated astrocytes (AT2A), but not ammonia per se, resulted in reduced levels of neuronal PSD95, synaptophysin and NMDA-nr1, as well as reduced synaptic density and dendritic complexity. Noteworthy, pharmacological inhibition of GMF, or silencing GMF by CRISPR reversed the defective neuronal integrity post-exposure of neurons to CM from ammonia-treated astrocytes in vitro. CONCLUSIONS: These findings strongly suggest that increased levels of GMF post-CLF may negatively impact neuronal integrity that may ultimately contribute to the neurobehavioral/cognitive and motor deficits observed in CHE. We anticipate that our studies aimed at a better understanding of the molecular mechanisms involved in the development of AT2A, and its impact on neuronal integrity in CHE, will greatly facilitate the identification of agents capable of ameliorating this debilitating condition.

P: 68 Brain Regional Susceptibility to Oxidative Stress in a Rat Model of Chronic Hepatic Encephalopathy: In-Vivo 1H MRS, Ex-Vivo ESR Spectroscopy and Histology Findings

BACKGROUND: Oxidative stress (OS) is believed to be an important feature in the pathogenesis of chronic hepatic encephalopathy (CHE).1 In CHE impaired ammonium clearance by the diseased liver leads to brain glutamine accumulation. In-vitro, affected ammonium detoxification together with glutamine induces reactive-oxygen-species (ROS) generation associated with astrocyte impairment.2,3 ROS play an important role in cellular signalling, synaptic-plasticity, learning and memory. When in excess, they cause cellular damage.4,5 Systemic oxidative stress was previously shown in bile-duct-ligated rats (BDL). Using in-vivo-longitudinal 1H-MRS we previously observed the indirect presence of OS as a decrease of brain Asc in the hippocampus and cerebellum of BDL rats (model of CHE).6 We aimed to validate these findings using for the first time ex-vivo electron spin (ESR) spectroscopy and histological measures to assess OS levels. METHODS: In-vivo-1H-MRS: Cerebellum/hippocampus of adult rats were scanned before BDL and after every 2-weeks up to week 6 (n = 18) at 9.4T-MR (Varian/Magnex-Scientific) using SPECIAL-sequence 7 (TE = 2.8 ms). Ex-vivo-ESR: ESP300E (Bruker-BioSpin) was used for intracellular superoxide anion detection. Hippocampus/cerebellum were extracted at 6weeks post-BDL/sham-surgery (n = 9), incubated in medium with 10 mM-CMH-cell-permeable spin-trap (Noxygen GmbH). Immunohistochemistry (ICH): GPX1 (anti-oxidative-enzyme) staining was performed (n = 6). RESULTS: The increase in plasma NH4+ and bilirubin confirmed the presence of chronic liver disease. A ∼80% increase in brain glutamine was measured at week6, while Asc showed a stronger decrease in cerebellum (−32% at week 6, P &lt; 0.001) (Figure 1a). ESR revealed differences in redox-state between the two brain regions (∼31% higher in cerebellum, P &lt; 0.004) (Figure 1b). However, the relative change in both regions between BDL and shams was similar ∼42%. The significant increase of hippocampal/cerebellar OS in BDL (P &lt; 0.01, P &lt; 0.001) corroborate the 1H-MRS findings of decreased Asc concentrations (Figure 1a). ICH with GPX1-enzyme,8,9 revealed an increase activity in Purkinje and granular-cell-layer of BDL cerebellum (Figure 1c). Purkinje-cells also showed shrinking soma (BDL: 8.04 ± 1.8 µm2, sham: 12.5 ± 1.2 µm2, P &lt; 0.00001). Elevated GPX1 in cerebellum suggests that GSH-synthesis may increase (confirmed by increased GSH in 1H MRS, Figure 1a) in response to OS-related injury. Elevated OS might suggest that ROS could lead to brain functions disruption.10–12 CONCLUSIONS: Our results showed for the first time the presence of central OS in BDL rats at 6-weeks post-surgery. Changes varied according to brain region and proved a different susceptibility of cerebellum and hippocampus to CHE, reflected by a relationship between increased OS and interrupted antioxidant-defence-system. OS is involved in the propagation of cellular injury and may be an important factor in the aetiology of the CHE.