Stages Of Hepatic Encephalopathy Research Articles

Diagnostic role of serum brain-derived neurotrophic factor in HCV cirrhotic patients with minimal hepatic encephalopathy with and without schistosomiasis

Abstract Background Liver cirrhosis (LC) advances from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis). Up to 80% of patients with LC may experience minimal hepatic encephalopathy (MHE), which is the first stage of hepatic encephalopathy (HE). Due to the lack of serum indicators, the diagnosis of MHE is frequently based on neuropsychometric tests. Therefore, this study aimed to evaluate the role of brain-derived neurotrophic factor (BDNF) as a diagnostic marker for MHE in HCV cirrhotic patients with or without hepatic schistosomiasis. Patients and methods The study consisted of 60 patients with divided into 3 groups (20 patients with HCV-related LC with overt HE, 20 patients with HCV-related LC without overt HE, and 20 patients with HCV-related LC and hepatic schistosomiases co-infection without overt HE) as well as 20 healthy controls. Patients without overt HE were evaluated for MHE by psychometric tests (trail making tests A and B). Serum BDNF was measured in all patients as well as healthy controls. Results Serum BDNF was found to be significantly lower in patients with LC regardless of etiology than in healthy controls; however, no statistically significant difference was found between patients with and without overt HE. Upon subdivision of patients without overt HE into “normal” and “deficient” using psychometric tests, serum BDNF was found to be significantly lower in patients with overt as well as those with “deficient” psychometric tests (have MHE). Serum BDNF had a sensitivity of 65.85% and specificity of 84.62%, and positive predictive value (PPV) was 82.0%, and negative predictive value (NPV) was 70.0% for diagnosis of MHE. Conclusion Serum BDNF concentration was found to be significantly lower in patients with deficient psychometric tests having either overt or covert HE which suggests that serum BDNF can be used as a diagnostic marker for MHE.

Association between Serum Electrolyte Level and Outcomes among Hospitalized Liver Cirrhosis Patients Presented with Hepatic Encephalopathy Admitted at a Tertiary Care Hospital

Background: Hepatic encephalopathy is the most common and debilitating complication among the patients with cirrhosis. Electrolyte derangement is greatly related to recurrence and outcome of patients hospitalized with hepatic encephalopathy. Objective: This study was aimed to find out the association between these two variables in our setting. Methodology: The study was a cross-sectional study and conducted among 100 patients admitted with hepatic encephalopathy. Diagnosis and staging of hepatic encephalopathy were done based on West Haven staging, and severity of liver cirrhosis by the MELD (Model for End-Stage Liver Disease) scoring, and the outcomes were determined by the condition of the patients during discharge. Baseline serum electrolyte level was done for all the study participants. Results: Among 100 patients, male-female ratio was 7:3 with an average (standard deviation) age 56.25(±14.8) years. Most common causes of hepatic encephalopathy were infection (40.0%), gastrointestinal bleeding (30.0%), electrolyte abnormality (30.0%). Outcomes of hepatic encephalopathy were complete recovery (75.0%), needed ICU admission (15.0%) and death (10.0%). This study found no co-relation between baseline electrolyte and complete recovery of these patients and no association with the outcome of the patients. Conclusion: Baseline serum electrolyte have no significant influence on recovery of the patients with hepatic encephalopathy with liver cirrhosis. Journal of Current and Advance Medical Research, January 2023;10(1):41-46

Investigation of therapeutic effects of rhubarb decoction retention enema on minimal hepatic encephalopathy in rats based on 16S rDNA gene sequencing and bile acid metabolomics

Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE), with high incidence and a high rate of clinically missed diagnosis. Early diagnosis of MHE and effective clinical intervention are of great importance. Rhubarb decoction (RD)-induced retention enema can effectively improve the cognitive function of patients with MHE, whereas disturbances in the enterohepatic circulation of bile acid (BAs) can induce MHE. However, the molecular mechanisms underlying the therapeutic effects of RD have not been examined from the perspective of intestinal microbiota and bile metabolomics. In this study, we investigated the effects of RD-induced retention enema on intestinal microbiota and bile metabolites in rats with CCl4- and TAA-induced MHE. RD-induced retention enema significantly improved liver function, reduced blood ammonia levels, alleviated cerebral oedema and restored cognitive function in rats with MHE. In addition, it increased the abundance of intestinal microbes; partially reversed the disorder in the composition of intestinal microbiota, including the Bifidobacterium and Bacteroides genera; and regulated BA metabolism, such as taurine combined with increased BA synthesis. In conclusion, this study highlights the potential importance of BA enterohepatic circulation for RD to improve cognitive function in MHE rats, providing a new perspective on the mechanism of this herb. The findings of this study will facilitate experimental research on RD and help to develop RD-based strategies for clinical application.

Study of serum zinc level in liver cirrhosis and its correlation with stages of hepatic encephalopathy

Study of serum zinc level in liver cirrhosis and its correlation with stages of hepatic encephalopathy

Assessment of excessive daytime sleepiness in cirrhotic patients

Background. It is known that alterations of the sleep-wake cycle are present from the early stages of hepatic encephalopathy (starting with grade I on the West Haven criteria). However, minimal hepatic encephalopathy (which is not included in the West Haven criteria) defines the earliest form of HE, with no obvious clinical manifestations, but with subtle alterations in cognitive domains such as attention, visuo-spatial perception, psychomotor speed and response inhibition. Aim. To determine if liver cirrhosis in otherwise asymptomatic individuals (without clinically manifest hepatic encephalopathy) is associated with an increased risk of altered sleep rhythm or excessive daytime sleepiness. Additionally, to determine if this risk is correlated with liver disease severity or other clinical and biological parameters. Material and methods. Cross-sectional study involving 25 adult patients with liver cirrhosis. Patients were evaluated through a standard neurological examination and with the Epworth Sleepiness Scale. Liver disease severity was measured using the MELD and Child-Pugh scores. Blood ammonia levels were also measured. Results. Mean age of the patients was 50±12 years-old. There was a predominance of males (68%, n=17). Mean MELD score was 17±7 points. Mean Child-Pugh score was 8±2 points. Mean blood ammonia level was 34±17 μg/dL. Subjective daytime somnolence was reported by 24% of patients (n=6). Mean ESS score was 6±5 points. No correlation was noted between the ESS scores and liver disease severity as measured by the Child-Pugh and MELD scores. Only three patients (12%) scored over 10 points on the ESS (none of them obese) and were consequently diagnosed with excessive daytime sleepiness (EDS). This proportion falls into the accepted prevalence of EDS in the general population. Conclusions. In our study, liver cirrhosis was not associated with a higher prevalence of excessive daytime sleepiness than in the general population.

Progressive Brain Structural Impairment Assessed via Network and Causal Analysis in Patients With Hepatitis B Virus-Related Cirrhosis

ObjectivesThis research amid to elucidate the disease stage-specific spatial patterns and the probable sequences of gray matter (GM) deterioration as well as the causal relationship among structural network components in hepatitis B virus-related cirrhosis (HBV-RC) patients.MethodsTotally 30 HBV-RC patients and 38 healthy controls (HC) were recruited for this study. High-resolution T1-weighted magnetic resonance imaging and psychometric hepatic encephalopathy score (PHES) were evaluated in all participants. Voxel-based morphometry (VBM), structural covariance network (SCN), and causal SCN (CaSCN) were applied to identify the disease stage-specific GM abnormalities in morphology and network, as well as their causal relationship.ResultsCompared to HC (0.443 ± 0.073 cm3), the thalamus swelled significantly in the no minimal hepatic encephalopathy (NMHE) stage (0.607 ± 0.154 cm3, p <0.05, corrected) and further progressed and expanded to the bilateral basal ganglia, the cortices, and the cerebellum in the MHE stage (p < 0.05, corrected). Furthermore, the thalamus swelling had a causal effect on other parts of cortex-basal ganglia-thalamus circuits (p < 0.05, corrected), which was negatively correlated with cognitive performance (r = −0.422, p < 0.05). Moreover, the thalamus-related SCN also displayed progressive deterioration as the disease advanced in HBV-RC patients (p < 0.05, corrected).ConclusionProgressive deterioration of GM morphology and SCN exists in HBV-RC patients during advanced disease, displaying thalamus-related causal effects. These findings indicate that bilateral thalamus morphology as well as the thalamus-related network may serve as an in vivo biomarker for monitoring the progression of the disease in HBV-RC patients.

Diagnosis and Management of Pediatric Acute Liver Failure: ESPGHAN and NASPGHAN 2022

Guidelines for management of pediatric acute liver failure (PALF) were recently published by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). We, herein, update the readers about the diagnosis and management of PALF with emphasis on the changes in assessment and staging of hepatic encephalopathy, administration and goals of supportive therapy, frequency of monitoring, and management of complications.

Клиническое значение определения уровня аммония в диагностике печеночной энцефалопатии у пациентов с заболеваниями печени

The paper presents the results of a survey of 35 patients with liver diseases of various etiologies hospitalized in Gastroenterology Department of Republic Clinical Hospital in Kazan. The patients were distributed according to etiology: liver cirrhosis — 28 (80%), acute hepatitis — 5 (14.3%), after liver transplantation — 2 (5.7%). The patients underwent a complete clinical examination, and psychometric tests were additionally used to assess the stage of hepatic encephalopathy. Blood ammonium level was determined in all patients using the PocketChem BA PA-4140 blood ammonia meter. Connect-the-Numbers Test revealed encephalopathy in 97.1% of patients with liver diseases, while latent hepatic encephalopathy was observed in 47% cases. According to the West-Haven criteria, hepatic encephalopathy was diagnosed in 80% patients. Hyperammonemia was determined in 80% of patients with liver diseases. There was some relationship between the ammonium level and the stage of hepatic encephalopathy.

EFFECTS OF PROTON PUMP INHIBITORS ON THE DEGREE OF DEVELOPMENT OF LIVER ENCEPHALOPATHY IN PATIENTS WITH LIVER CIRROSIS

In this study, we attempted to determine whether proton pump inhibitor (PPI) use in patients with hepatic encephalopathy was predisposed to more severe stages of hepatic encephalopathy according to West Haven criteria. We found that chronic use of PPIs in patients with cirrhosis of the liver and gastroduodenal pathology was associated with significantly higher mean West Haven criteria for hepatic encephalopathy compared with patients who did not use PPIs. Our data also showed that patients with cirrhosis of the liver receiving PPIs have longer hospital stays, with increased morbidity and mortality during their hospital stay.

Results of using L-ornitin-L-aspartate in the treatment of hepatic encephalopathy in liver transplantation

The aim was to study the results of using various treatment regimens for hepatic encephalopathy for patients with liver cirrhosis before and after liver transplantation and the effect on the incidence and severity of hepatic encephalopathy in the perioperative period, and on the posttransplantation course.Material and methods. Fifty four patients with cirrhosis of various etiologies and the presence of significant hepatic encephalopathy undergoing living donor liver transplantation were included in the study. In the comparison group, patients took lactulose and rifaximin. In the main group, patients took lactulose and rifaximin in combination with L-ornithine-L-aspartate in the preoperative period, and L-ornithine-L-aspartate after liver transplantation for 5 days.Results. The use of L-ornithine-L-aspartate in the complex therapy of hepatic encephalopathy led to significantly reduced time of performing the Number Connection Test, the improvement of cognitive functions in patients by the Montreal Cognitive Assessment, a decreased incidence of stage II–III hepatic encephalopathy and an increased incidence of stage 0-I hepatic encephalopathy in the preoperative period. In the postoperative period, patients of the main group showed a rapid decrease in the severe stages of hepatic encephalopathy (stage II–III) towards less severe forms (stage 0–I) on the 3rd, 5th and 7th days after liver transplantation, and also a faster recovery of cognitive functions, an earlier adequate recovery of consciousness, muscle tone, an earlier possibility of extubation, a shorter length of stay in the intensive care unit, and a decreased postoperative hospital length of stay relatively to the patients of the comparison group.Conclusion. The use of L-ornithine-L-aspartate in the combination therapy for hepatic encephalopathy in the peritransplantation period leads to a significant decrease of the incidence and severity of hepatic encephalopathy, accelerates rehabilitation of patients, reduces postoperative hospital length of stay.

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis.

Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.

НАСЛЕДСТВЕННАЯ НЕКОНЪЮГИРОВАННАЯ ГИПЕРБИЛИРУБИНЕМИЯ (СОЧЕТАНИЕ СИНДРОМА КРИГЛЕРА-НАЙЯРА II ТИПА И СИНДРОМА ЖИЛЬБЕРА)

Background. Enzymopathic jaundices are manifested by intermittent hyperbilirubinemia, no changes in the structure of the liver, no hemolysis, Rh-conflict as well as cholestasis being noted. These jaundices include Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II and Gilbert's syndrome. They are characterized by an autosomal recessive inheritance due to the presence of mutations and polymorphisms in uridine 5'-diphosphate-glucuronosyltransferase gene (UGT1A1) leading to a decrease of the enzyme activity or to its complete loss. Objective. To demonstrate the peculiarities of diagnosis and treatment of a rare case of hereditary unconjugated hyperbilirubinemia - a combination of Crigler-Najjar syndrome type II and Gilbert's syndrome. Material and methods. Clinical observation of a patient G. aged 19, who was examined and treated at the Department of gastroenterology of a multidisciplinary hospital in Moscow in January 2021. Results. The patient G. has had icteric sclerae and skin since birth; he occasionally suffers from easy fatigability and general malaise. Physical examination revealed no changes (except for icteric discoloration). An increase in unconjugated bilirubin up to 270 μmol/L (median - 170 μmol/L) was detected. The molecular genetic study of UGT1A1 gene identified mutations in exon 4 Val378Asp (2002) and Arg108Cys as well as polymorphism 6/7TA in the promoter region, confirming the diagnosis of autosomal recessive inherited disease – a combination of Crigler Najjar syndrome type II and Gilbert's syndrome (heterozygous state), complicated by the development of hepatic encephalopathy stage 2. There was noted a significant decrease in unconjugated bilirubin up to 170.5 μmol/L, as well as improvement in general condition – reduced fatigue and weakness during the treatment with microsomal enzyme inducer (phenobarbital) and hyperammonemia corrector (ornithine aspartate). Conclusions. The use of molecular genetic analysis allows tailoring strategies for patient-specific disease diagnostics, treatment and prevention. The preservation of quality of life within satisfactory level is achieved through elimination of adverse effects provoking the development of this syndrome and through control of risk factors.

A dynamic prediction model for prognosis of acute-on-chronic liver failure based on the trend of clinical indicators

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome, and sequential assessments can reflect its prognosis more accurately. Our aim was to build and validate a new scoring system to predict short-term prognosis using baseline and dynamic data in ACLF. We conducted a retrospective cohort analysis of patients with ACLF from three different hospitals in China. To construct the model, we analyzed a training set of 541 patients from two hospitals. The model’s performance was evaluated in a validation set of 130 patients from another center. In the training set, multivariate Cox regression analysis revealed that age, WGO type, basic etiology, total bilirubin, creatinine, prothrombin activity, and hepatic encephalopathy stage were all independent prognostic factors in ACLF. We designed a dynamic trend score table based on the changing trends of these indicators. Furthermore, a logistic prediction model (DP-ACLF) was constructed by combining the sum of dynamic trend scores and baseline prognostic parameters. All prognostic scores were calculated based on the clinical data of patients at the third day, first week, and second week after admission, respectively, and were correlated with the 90-day prognosis by ROC analysis. Comparative analysis showed that the AUC value for DP-ACLF was higher than for other prognostic scores, including Child–Turcotte–Pugh, MELD, MELD-Na, CLIF-SOFA, CLIF-C ACLF, and COSSH-ACLF. The new scoring model, which combined baseline characteristics and dynamic changes in clinical indicators to predict the course of ACLF, showed a better prognostic ability than current scoring systems. Prospective studies are needed to validate these results.

Clinical features of patients with acute-on-chronic liver failure and bacterial infection and influencing factors for prognosis

Objective To investigate the clinical features of infection in patients with acute-on-chronic liver failure (ACLF) and bacterial infection and the influencing factors for 90-day survival rate. Methods The patients with ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2015 were enrolled, and related clinical data were collected and analyzed, including infection time and site, microbial culture, biochemical parameters and inflammatory markers, and 28- and 90-day prognosis after infection. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The life-table method was used to plot survival curves. The indices affecting prognosis in the univariate analysis were further included in the multivariate logistic regression analysis. Results A total of 1074 patients with ACLF were admitted, among whom 609 had bacterial infection, and the incidence rate of bacterial infection was 56.7%. Among these 609 patients, 16 underwent liver transplantation within 90 days and related data statistics were obtained for the remaining 593 patients. As for infection site, among the patients with infection, 70.15% had abdominal infection, 41.15% had pulmonary infection, 11.97% had sepsis, 5.40% had urinary system infection, 4.89% had thoracic infection, and 8.6% had infection at other sites. Among the patients with infection, 64.76% had infection at a single site. The positive rates of microbial culture of ascites, phlegm, urine, and pleural effusion were 22.70%, 52.82%, 40.63%, and 35.71%, respectively. Escherichia coli was the most common bacterium in ascites and accounted for 43.82%; Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii accounted for 22.67%, 24.00%, and 22.67%, respectively, in phlegm; Escherichia coli, Klebsiella pneumoniae, and Staphylococcaceae accounted for 33.80%, 29.58%, and 15.49%, respectively, in blood culture. The 90-day survival rate after infection was 38.11% (226/593) in the patients with ACLF, and the multivariate logistic regression analysis showed that age (P=0.006), stage of hepatic encephalopathy (HE) (P Conclusion There is a high incidence rate of infection in patients with ACLF. The 90-day survival rate is relatively low, and the presence of AKI, HE stage III or above, and advanced liver failure may indicate poor prognosis.

Clinical and epidemiological characteristics of hepatic cirrhosis of hepatitis C virus etiology in the early stages of its formation

Background. Currently, the incidence of viral cirrhosis of the liver increases significantly, presenting an essential medical and social problem. This study aimed to clarify the clinical and epidemiological characteristics of hepatic cirrhosis of hepatitis C virus (HCV) etiology in the early stages of formation to improve the quality of diagnosis using a sample of patients from the regional hepatological center in Krasnodar (Specialized Clinical Infectious Diseases Hospital).&#x0D; Methods. In 2018, 1,307 patients with liver diseases of viral etiology were examined and treated at the hepatological center. A retrospective analysis of the monitoring results of 153 patients with hepatic cirrhosis of viral C etiology with HCV replication was performed; patients with mixed etiology of cirrhosis were excluded from the study. The enrolled participants included 89 women (58.2%) and 64 men (41.8%). The average age of the patients was 53.5 0.93 years. In accordance with the ChildPugh classification of hepatic cirrhosis, class A (I) was diagnosed in 92 (60.1%) patients, and class B (II) was revealed in 53 (34.6%) patients.&#x0D; Results. In 59.5% of cases, viral liver damage was first detected at the stage of outcome to cirrhosis. In 1/3 (32.5%) of the patients, the diagnosis of hepatic cirrhosis was established in the year of visit, and in another 27%, it was established during the first three years from the date of detection of hepatitis C markers. In less than in 1/5 (18.3%) of the patients, 924 years have passed from the discovery of hepatitis C markers to the establishment of hepatic cirrhosis. During the three-year follow-up period, the progression of cirrhosis with the transition to the next stage occurred in 6.5% of cases. In residents of Krasnodar Territory, among the leading epidemiological factors, including a monofactor epidemiological history and multifactorial nature with almost the same frequency, the alleged cause of infection was surgery (43%45%). Prosthetics, dental sanitation, and blood transfusion were indicated as possible infection factors with high incidence. Factors, such as drug addiction, childbirth, tattoos, occupational injuries in medical personnel, and abortions, were recorded in isolated cases. In the early diagnostics of compensated class A cirrhosis, the increased contents of alanine and aspartate aminotransferases showed diagnostic value. Mild increases in the levels of alpha-fetoprotein and direct bilirubin, moderate decreases in prothrombin index and platelets, dilation in the diameter of the portal (v. portae) and splenic (v. lienalis) veins to borderline values with an upper limit of norm with an increased size of the spleen, and esophageal varices, and development of the initial stage of hepatic encephalopathy were also noted. The presence of extrahepatic manifestations in 12% of the patients should be considered.&#x0D; Conclusion. Despite the high infection rate of the population with hepatitis C virus, late diagnostics of liver damage often occurred, and this finding is partly due to the late action of patients in seeking medical help. On the other hand, the widespread introduction of mandatory medical examination led to the active identification of sick people. For timely diagnosis, the presence of a history of risk factors for hepatitis infection must be considered, and attention must be focused on the abnormalities of blood biochemical parameters, ultrasound, and fibrogastroduodenoscopy data.

Clinical-neuropsychological features of the hepatic encephalopathy formation

35 patients with different stages of the hepatic encephalopathy on the background of the chronic hepatitis at the age of 45.2 ± 5.8 years were examined. The investigation complex included neurological, psychometric (numbers connection test, SDMT number-symbol test, Schulte tables, Montreal cognitive function evaluation scale, HADS scale), and instrumental (EEG and MRI of the brain) examination. The findings showed that early clinical manifestation of hepatic encephalopathy included mild cognitive impairments, sleep disturbances (initial manifestations of impaired consciousness), emotional disorders (asthenic syndrome, anxiety) and impaired fine motor movements (changes of handwriting and fine coordination). According of the psychometric testing results the signs of the hepatic encephalopathy latent stage were detected including an impairment of the attention (due to numbers connection test results), a decrease of the cognitive processes speed and a violation of visual short-term memory (SDMT), difficulty in delayed reproduction of the information, a violation of fine motor movements (change handwriting). Disturbance of the brain bioelectrical activity was characterized by slowing the frequency of the alpha rhythm, an increase in the slow-wave activity index, smoothed zonal differences, and recording of hypersynchronous alpha waves or three-phase waves, which were determined already in the early stages of the disease. Comparing the psychometric testing data and the neuroimaging results, it was noted that the identified cognitive disorders, including those at the latent stage of hepatic encephalopathy, were accompanied by the frontal and parietal lobes cortex hypotrophy and the subcortical structures damage. Progression of the hepatic encephalopathy was accompanied by increased cognitive, emotional, motor and sleep disorders, which was confirmed by the results of psychometric testing, and also coincided with the functional and morphological disorders worsening of the brain according to the neurophysiological and neuroimaging examinations.

FEATURES OF CEREBRAL HEMODYNAMICS AND MANIFESTATIONS OF HEPATIC ENCEPHALOPATHY IN CIRRHOSIS OF VIRAL ETIOLOGY AT DIFFERENT COMPENSATION STAGES WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION

Aim . To study the features of the parameters of cerebral hemodynamics in extra and intracranial regions in viral hepatic cirrhosis A, B, C classes according to Child-Pugh with different serum levels of interleukin-2, interleukin-6 and tumor necrosis factor alpha and preserved left ventricular ejection fraction for improvement of diagnostics of stages of chronic hepatic encephalopathy. Material and methods . 107 patients with viral cirrhosis A, B, C classes according to Child-Pugh with different serum levels of interleukin-2, interleukin-6 and tumor necrosis factor alpha were included into the study. The parameters of hemodynamics in common carotid and middle cerebral arteries of the first order of both hemispheres as well as the parameters of echocardiography were studied in all patients. Evaluation of hepatic encephalopathy stages was carried out by the West-Haven symptoms scale and the Reitan test (Number Connection Test) according to the recommendations of the Working group of the XI-th World Gastroenterology Congress. Results . Reduction in the compensation of hepatic cirrhosis A and C classes was accompanied by a thickening of the intima-media complex in the common carotid arteries from 0.69±0.21 mm to 0.79±0.35 mm, respectively. The hemispheric asymmetry of the mean linear blood flow velocity tended to increase from 25.1±2.42% in cirrhosis A class to 39.5±7.94% in cirrhosis C class. The greatest disorders of the hemodynamics in the middle cerebral arteries were observed in hepatic cirrhosis C class due to changes in the linear blood flow velocity parameters, increase in the hemispheric asymmetry of the average linear flow rate up to 33.9±10.5%, reduction in resistance and pulsatility indices to 0.49±0.22 and 1.02±0.21, respectively. Conclusion . Chronic hepatic encephalopathy of all stages can occur in the presence of discirculatory disorders with the development of chronic cerebrovascular insufficiency in viral hepatic cirrhosis A, B, C classes with different serum levels of interleukin-2, interleukin-6 and tumor necrosis factor alpha and preserved systolic function of the left ventricle. The duration of the Number Connection Test more than 200 s, blood flow hemispheric asymmetry more than 40%, decrease in blood flow velocity parameters and vascular resistance indices in the middle cerebral artery below the reference values are associated with a poor prognosis of hepatic encephalopathy. The degrees of cognitive and discirculatory disorders are related with the stages of hepatic cirrhosis compensation. An increase in the degree of cognitive impairments (from ability to logical thinking and attention to disorientation in time and space) is observed in discirculatory disorders and decrease in the stage of cirrhosis compensation.

Acute hepatic failure with encephalopathy in children

Introduction: Hepatic encephalopathy is a serious and likely to be reversible neurophyschiatric state in the patient of liver failure. Acute hepatic failure is a life-threatening condition in children. Objectives: The study analyses the clinical spectrum, prognosis and factors determining the prognosis of children with acute hepatic failure and associated encephalopathy in a tertiary level hospital. Methodology: Thirty two children (18 males and 14 females) were presented with the diagnosis over a two year period. It is a Prospective study. Results: The commonest cause of acute hepatic failure was hepatitis A virus found in 30% of cases. Only 30% (9 out of 32) children could be survived, in which mostly came in hepatic encephalopathy Stage I and II. Hemorrhagic manifestations were significantly more (P=0.002) in died in contrast to survived. Conclusion: Hepatic failure is a condition associated with high mortality primarily in absence of hepatic transplantation facilities. Focus of efforts should be in providing preventive steps such as immunization and society education.

Abnormal cortical synaptic plasticity in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) represents the earliest stage of hepatic encephalopathy (HE). MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, while obvious clinical manifestations are lacking. In the present study, we aimed at assessing whether subjects with MHE showed alterations in synaptic plasticity within the motor cortex. Previous findings suggest that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. We employed therefore the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Fifteen patients with MHE and 15 age- and sex-matched cirrhotic patients without MHE were recruited. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min. In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude. On the contrary, in patients with MHE the MEP amplitude was slightly reduced after PAS. These findings demonstrated that associative sensorimotor plasticity, an indirect probe for motor learning, is impaired in MHE patients.

Resting-state functional connectivity abnormalities correlate with psychometric hepatic encephalopathy score in cirrhosis

Background & aimsNeurocognitive impairment is a common complication of cirrhosis and regarded as the important characteristic for early stage of hepatic encephalopathy (HE). This study aimed to investigate the changes in brain network centrality of functional connectivity among cirrhotic patients and uncover the mechanisms about early HE. MethodsTwenty-four cirrhotic patients without overt HE and 21 healthy controls were enrolled and underwent resting-state fMRI and Psychometric Hepatic Encephalopathy Score (PHES) tests. Whole-brain functional network was constructed by measuring the temporal correlations of every pairs of brain gray matter voxels; and then voxel-wise degree centrality (DC), an index reflecting importance of a node in functional integration, was calculated and compared between two groups. A seed-based resting-state functional connectivity (RSFC) analysis was further performed to investigate abnormal functional connectivity pattern of those regions with changed DC. ResultsCompared with controls, the cirrhotic patients had worse performances in all neurocognitive tests and lower PHES score. Meanwhile, patients showed decreased DC in bilateral medial prefrontal gyrus and anterior cingulate cortex, left middle frontal gyrus, and bilateral thalamus; while increased DC in right middle occipital gyrus and parahippocampal gyrus/inferior temporal gyrus. The seed-based RSFC analyses revealed that the relevant functional networks, such as default-mode and attention networks, visual network, and thalamo-cortical circuits, were disturbed in cirrhotic patients. The DC changes were correlated with PHES score in patient group. ConclusionsOur findings further confirm brain network disorganization in cirrhotic patients with neurocognitive impairments and may provide a new perspective for understanding HE-related mechanisms.