Encephalopathy In Cirrhotic Patients Research Articles

Prevalence and risk factors for minimal hepatic encephalopathy in cirrhotic patients with different etiologies

AbstractAimsMinimal hepatic encephalopathy (MHE) significantly affects the prognosis of patients with cirrhosis. This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.MethodsThis multicenter, cross‐sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25, 2021, to January 10, 2023 (Trial registration: https://clinicaltrials.gov/[NCT05140837]). The patients' demographics, etiologies of cirrhosis, and laboratory test results were collected. The psychometric hepatic encephalopathy score (PHES) was determined in all patients to screen for MHE. Multivariate logistic analyses were performed to identify the risk factors for MHE.ResultsIn total, 736 patients with cirrhosis were analyzed. The prevalence of MHE was 42.0% (n = 309). The primary etiology among all patients was hepatitis B virus (HBV)‐related cirrhosis (71.9% [529/736]). The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis (57.1% [40/70]) than in those with HBV‐related cirrhosis (40.6% [215/529], p = 0.009) or hepatitis C virus (HCV)‐related cirrhosis (38.2% [26/68], p = 0.026). Age (odds ratio [OR], 1.042; 95% confidence interval [CI], 1.024–1.059; p < 0.001), duration of education (OR, 0.935; 95% CI, 0.899–0.971; p = 0.001), etiology (OR, 1.740; 95% CI, 1.028–2.945; p = 0.039), and high MELD‐Na scores (OR, 1.038; 95% CI, 1.009–1.067; p = 0.009) were independent risk factors for MHE. When patients with cirrhosis of different etiologies were analyzed separately, the results showed that age (OR, 1.035; 95% CI, 1.014–1.057; p = 0.001) and duration of education (OR, 0.924; 95% CI, 0.883–0.966; p = 0.001) were risk factors for MHE among patients with HBV‐related cirrhosis, whereas age (OR, 1.138; 95% CI, 1.033–1.254; p = 0.009) and creatinine concentration (OR, 16.487; 95% CI, 1.113–244.160; p = 0.042) were risk factors for MHE in patients with HCV‐related cirrhosis. No risk factors for MHE were found in patients with autoimmune cirrhosis. For patients with alcoholic cirrhosis, the platelet count (OR, 1.014; 95% CI, 1.000–1.027; p = 0.045) was a risk factor for MHE. The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies. Patients with HBV‐related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis (p = 0.007 and p < 0.001), better on Number Connection Test B than those with HCV‐related cirrhosis (p = 0.020), and better on the line tracing test than those with autoimmune cirrhosis (p = 0.037).ConclusionThe etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE. The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies. Further studies are required to verify these findings.

Recurrence of portosystemic encephalopathy in cirrhotic patients and its risk factors.

Recurrent episodes of Portal Systemic Encephalopathy (PSE), poses a significant burden of illness on the patients and healthcare system. The objective of this study was to assess the recurrence of PSE in cirrhotic patients after index episode of PSE and to identify various risk factors associated with it. A retrospective, single-centre study was conducted at Aga Khan University Hospital over a span of one year. Patients who were admitted first time with PSE and admitted within three months of index PSE were enrolled in the study. Variables assessed were demographic data, associated comorbid conditions, aetiology of cirrhosis, Child-Turcotte-Pugh (CTP) score, Model of End-Stage Liver Disease (MELD) score, PSE grade, laboratory tests, ascites with spontaneous bacterial peritonitis (SBP), variceal bleeding. Statistical analysis was done and variables of those who developed recurrence were compared with those who did not. Fifty one patients were recruited. Thirty three (64.7%) were readmitted with PSE. On comparative analysis of both groups; infection, Meld score, low albumin, and raised total bilirubin showed significant P-value (<0.05). Identification of risk factors during assessment can reduce the recurrence of PSE. We would recommend to validate result of our study on a large scale prospectively.

Hyponatremia as A Prognostic Indicator for Hepatic Encephalopathy in Cirrhotic Patients

Hyponatremia as A Prognostic Indicator for Hepatic Encephalopathy in Cirrhotic Patients

Sub-Clinical Hepatic Encephalopathy in Cirrhotic Patients Subjected to Sedation with either Propofol or Midazolam‎

Sub-Clinical Hepatic Encephalopathy in Cirrhotic Patients Subjected to Sedation with either Propofol or Midazolam‎

Low adipose tissue index as an indicator of hepatic encephalopathy in cirrhotic patients following transjugular intrahepatic portosystemic shunt.

We aimed to investigate the predictive value of body compositions measured by CT, including skeletal muscle and adipose tissue, for hepatic encephalopathy (HE) in cirrhotic patients following transjugular intrahepatic portosystemic shunt (TIPS). Patients who underwent TIPS between November 2015 and April 2021 were included in this retrospective study. CT images taken at L3 were quantified for three body composition indexes (cm2/m2), visceral fat area index (VFAI), subcutaneous fat area index (SFAI), and skeletal muscle index (SMI) at baseline. Multivariable logistic regression models were conducted to assess associations between post-TIPS HE and body compositions. Nomograms based on the multivariable logistic regression models were developed and were evaluated from Calibration curves. Male patients had greater SMI, whereas SFAI and VFAI were higher in females (p < 0.001 for each). In sex stratified multivariate analyses after adjustment for other confounding variables, VFAI in males (p = 0.033) and SFAI in females (p = 0.003) were significant predictors of post-TIPS HE. Male patients with low VFAI (< 53.52cm2/m2) (OR 6.44; 95% CI 1.72-23.59; p = 0.006) and female patients with low SFAI (< 70.05cm2/m2) (OR 10.55; 95% CI 2.36-46.23; p = 0.002) had a higher risk of post-TIPS HE. Risk factors in the nomogram contributing to the male model included age, height, Child-Pugh score, and low VFAI; pre-albumin and low SFAI were contributed to female model. Body compositions could not only be noninvasively used for nutritional assessment, but also be utilized to predict HE risk of cirrhotic patients after TIPS.

Prevalence and Risk Factors of Covert Hepatic Encephalopathy in Cirrhotic Patients: A Multicenter Study in China.

We aimed to determine the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients from China and to investigate its risk factors. A multicenter prospective observational study was conducted from January 2021 to March 2022 in 16 centers to investigate the impact factors of CHE and establish a prognostic model for CHE episodes. Totally 528 patients were enrolled in the analysis. Based on the anomalies of both PHES and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Advanced age (OR = 1.043; 95% CI: 1.022-1.063, P < 0.001), low education level (OR = 0.891; 95% CI: 0.832-0.954, P = 0.001), poor Child-Pugh score (OR = 1.142; 95% CI: 1.029-1.464, P = 0.025), and high BUN concentration (OR = 1.126; 95% CI: 1.038-1.2221, P = 0.004) were associated with CHE episodes. According to the chronic Liver Disease Questionnaire (CLDQ), CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), which reflected the poor health-related quality of life (HRQoL). According to the stepwise Cox regression hazard model analysis, we established a nomogram for determining the probabilities of CHE episodes, and the AUC was 0.733 (95% CI: 0.679-0.788) in the training cohort and 0.713 (95% CI: 0.628-0.797) in the validation cohort. CHE was a common complication of cirrhosis in China. It is necessary to carry out more large-scale studies with longer follow-up periods to determine the natural history of Chinese CHE patients. This article is protected by copyright. All rights reserved.

Hepatic Encephalopathy in Cirrhotic Patients With Bacterial Infections: Frequency, Clinical Characteristics, and Prognostic Relevance

Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI. A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation. 172 patients (age 57±13, model of end-stage liver disease [MELD]-sodium 22±8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P= 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality. HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.

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.

Hepatic Encephalopathy in Cirrhotic Patients and Risk of Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-Analysis.

Background Hepatic encephalopathy (HE) is a neurological and psychiatric syndrome. Recent evidence suggests that HE is not only a disease of the liver and brain but is also related to the gut. Small intestinal bacterial overgrowth (SIBO) is well known to be associated with cirrhosis, but the relationship between SIBO and HE is unclear. We conducted this comprehensive systematic review and meta-analysis to determine the association between SIBO and HE in cirrhotic patients. Methods We conducted a comprehensive literature search of all studies on the association of SIBO and HE in cirrhotic patients using the PubMed and Embase electronic databases. Studies were screened, and relevant data were extracted and analysed. We calculated the number of cases of SIBO in patients with HE and controls. We then compared the prevalence of SIBO between the two groups to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Funnel plots were constructed to identify potential publication bias. Results Six studies with 414 participants (219 HE patients and 195 controls) met the inclusion criteria. The prevalence of SIBO in cirrhotic patients with HE was significantly higher than that in those without HE. The combined OR was 4.43 (95% CI 1.73-11.32, P = 0.002). The heterogeneity was moderate (I2 = 66%), and the funnel plot suggested no significant publication bias. Subgroup analysis showed that the OR was 1.95 (95% CI 0.63–6.09) in studies using the lactulose breath test (LBT) and 7.60 (95% CI 3.50–16.50) in studies using the glucose breath test (GBT). The prevalence of SIBO in cirrhotic patients was also related to the severity of liver disease. Conclusions Our meta-analysis identified a strong association between SIBO and HE, and the risk of SIBO was 4.43 times higher among cirrhotic patients with HE than among those without HE. SIBO could be a predisposing factor for the development of HE in cirrhotic patients. Therefore, the importance of SIBO should be emphasized in patients with HE.

Frequency of Complications by Serum Sodium Level among Patients with Liver Cirrhosis

Background: Cirrhosis is a life-threatening and incurable condition. It is a leading cause of death and disease all over the globe. Fluctuations in blood sodium levels are a common consequence of advanced cirrhosis Objective: To determine frequency of complications by serum sodium level among patients with liver cirrhosis. Methodology: This descriptive Cross sectional study was carried out at the Department of Medicine, Khyber Teaching Hospital, Peshawar from Mar 1, 2021 to Aug 31, 2021. The severity of cirrhosis was measured using Child-Pugh Scores for all patients after a thorough history and examination. Blood samples from all patients were obtained under stringent aseptic conditions and sent to the hospital laboratory. The level of sodium in the serum was tested under the observation of a pathologist having more than 10 years of pathology experience. Results: In our study, amongst 210 subjects, 125 (59.52%) were males whereas 85(40.48%) were females. The spontaneous bacterial peritonitis among liver cirrhosis was observed in 42(20%) patients and Encephalopathy was observed in 48(22.9%) cases. Conclusion: Low levels of sodium in serum are a prevalent trait in individuals with cirrhosis, according to the findings of this research. Serum sodium concentrations ˂130 meq/l is associated with an increased risk of Spontaneous Bacterial Peritonitis and hepatic encephalopathy in cirrhotic patients. Keywords: Serum sodium, Hepatic Encephalopathy, Spontaneous Bacterial Peritonitis

Controlling nutritional status score as a new indicator of overt hepatic encephalopathy in cirrhotic patients following transjugular intrahepatic portosystemic shunt

<h2>Summary</h2><h3>Background & aims</h3> The Controlling Nutritional Status (CONUT) score is designed to assess the immune-nutritional status of patients. Poor nutritional status and inflammation may facilitate the development of hepatic encephalopathy (HE) in cirrhotic patients. However, it remains unknown whether the CONUT score is related to and can be used as a predictive marker for HE. The aim of this study was to investigate the association and predictive value of the CONUT score for overt hepatic encephalopathy (OHE) in cirrhotic patients following transjugular intrahepatic portosystemic shunt (TIPS). <h3>Methods</h3> A retrospective study of 77 patients with cirrhosis having undergone TIPS was performed at The First Hospital of Shanxi Medical University. Relevant patient data were collected from the medical records, and logistics regression analyses were performed to estimate the association between CONUT score and OHE. Restricted cubic spline models were further used to examine the shapes of the dose-response association. The area under curve (AUC) represented the test discriminative power of CONUT score and relevant clinical parameters. The Kaplan-Meier curve was used to compare the patient risk of OHE according to the cut-off CONUT score. <h3>Results</h3> During a median follow-up of 13 months, 41 patients (53.2%) experienced OHE events. The optimal cut-off value for the CONUT score of OHE was 5, with sensitivity and specificity values of 0.927 and 0.528, respectively (AUC = 0.815). The predictive power of CONUT score was higher than that of neutrophil lymphocyte ratio (NLR), Model for End-Stage Liver Disease (MELD) score, and Child-Pugh score based on time-dependent receiver operating characteristic (ROC) analysis. The high CONUT group (CONUT score ≥ 5) had significantly higher OHE prevalence (P < 0.001) than the low CONUT group (CONUT score < 5). The CONUT score was an independent predictor of OHE following TIPS (Odds Ratio (OR) = 7.3; 95% CI: 2.1–25.6; P = 0.002). Restricted cubic spline models showed that with an increasing CONUT score, the ln-transformed OR of OHE risk followed an increasing trend (P for overall association < 0.05). Meanwhile, logistic regression analysis with step method showed that history of OHE, blood ammonia, CONUT score, international normalised ratio (INR) and bilirubin were independent predictors of OHE following TIPS. <h3>Conclusion</h3> To our knowledge, this is the first study demonstrating that the CONUT score was directly correlated with OHE risk, and could serve as a reliable prognostic marker of OHE risk in cirrhotic patients following TIPS. The results suggest it could be beneficial in the evaluation and management of OHE.

The role of functional magnetic resonance imaging of the brain in the evaluation of hepatic encephalopathy in cirrhotic patients.

Hepatic encephalopathy (HE) is a complication of liver failure, with neurological manifestations ranging from minimal HE (MHE) to deep coma (overt HE). To demonstrate the role of functional magnetic resonance imaging (magnetic resonance spectroscopy [MRS] and apparent diffusion coefficient [ADC] value) in the assessment and grading of HE in cirrhotic patients. A prospective cohort study was conducted on three groups: group I - 20 healthy controls, group II - 25 cirrhotic patients with MHE, and group III - 25 cirrhotic patients with overt HE. Each group was subjected to MRS, diffusion-weighted imaging, and neuropsychological examinations. At 1H-MRS, the glutamate/glutamine complex (Glx), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and creatine (Cr) were determined in the basal ganglia or thalamus. The metabolic ratios and ADC values of Glx/Cr, MI/Cr, Cho/Cr, and NAA/Cr were determined. The brain metabolite Glx increased with a significant correlation to HE grade (p = 0.001). Other brain metabolites, such as Cho and mI, decreased significantly (p = 0.001). Two brain metabolites (NAA and Cr) remained unchanged across all HE grades and the control group (p = 0.47 and 0.38, respectively). There was an increase in the Glx/Cr ratio and a decrease in the mI/Cr and Cho/Cr ratios. In addition, ADC values were significantly higher in cirrhotic patients with HE than in the control group. ADC values and 1H-MRS are imaging modalities that have the potential to detect MHE and grade HE in cirrhotic patients.

Using machine learning methods to predict hepatic encephalopathy in cirrhotic patients with unbalanced data

ObjectiveHepatic encephalopathy (HE) is among the most common complications of cirrhosis. Data for cirrhosis with HE is typically unbalanced. Traditional statistical methods and machine learning algorithms thus cannot identify a few classes. In this paper, we use machine learning algorithms to construct a risk prediction model for liver cirrhosis complicated by HE to improve the efficiency of its prediction. MethodWe collected medical data from 1,256 patients with cirrhosis and performed preprocessing to extract 81 features from these irregular data. To predict HE in cirrhotic patients, we compared several classification methods: logistic regression, weighted random forest (WRF), SVM, and weighted SVM (WSVM). We also used an additional 722 patients with cirrhosis for external validation of the model. ResultsThe WRF, WSVM, and logistic regression models exhibited better recognition ability for patients with HE than traditional machine learning models (sensitivity> 0.70), but their ability to identify patients with uncomplicated HE was slightly lower (specificity approximately 85%). The comprehensive evaluation index of the traditional model was higher than those of other models (G-means> 0.80 and F-measure> 0.40). For the WRF, the G-means (0.82), F-measure (0.46), and AUC (0.82) were superior to those of the logistic regression and WSVM models, which means that it can better predict the incidence of HE in patients. ConclusionThe WRF model is more suitable for the classification of unbalanced medical data and can be used to construct a risk prediction and evaluation system for liver cirrhosis complicated with HE. The probabilistic prediction models of WRF can help clinicians identify high-risk patients with HE.

ATP-binding cassette transporters expression in rats with cirrhosis and hepatic encephalopathy

Pathophysiology of acute encephalopathy in cirrhotic patients is not completely understood. Factors implicated include ammonia, inflammation, various metabolic disorders and drug toxicity. Recent studies have evidenced an increased permeability of the blood-brain barrier (BBB) in models of chronic liver disease and encephalopathy, either to solutes, or to leukocytes. A modification of the expression of BBB ATP-Binding Cassette (ABC) transporters, actively transporting endogenous and exogenous components through the BBB, has been described in models of acute liver failure. We hypothesized that a modification of ABC transporters expression may contribute to drug-induced acute encephalopathy in cirrhosis. A rat model of cirrhosis induced by Bile Duct Ligation (BDL) was studied, and compared to a SHAM rat model. Rats were sacrificed and brains studied after decapitation. Genic expression of ABC transporters, including P-gp, BCRP, MRP1, MRP2, MRP4 and MRP5 was evaluated by RT-qPCR on isolated brain microvessels. Encephalopathy was assessed 6 weeks after surgery by a trail suspension test and an Open Field Test. BDL rats developed a histologically proven cirrhosis and displayed a higher ammonemia than SHAM rats (183 µmol/L vs 53 µmol/L, p=0.0003). BDL rats presented with encephalopathy shown by neurobehavioral tests. MRP2 was not detected neither in BDL nor in SHAM rats. There was a decrease in the genic expression of MRP5 6 weeks after surgery. Expressions of P-gp, BCRP, MRP1 and MRP4 were not different between the 2 groups. We suggest that acute encephalopathy in cirrhotic BDL rats may be associated to a modification of ABC transporter MRP5 on the BBB, that could be responsible for a decrease clearance of neurotoxic agents.

Role of lactulose for prophylaxis against hepatic encephalopathy in cirrhotic patients with upper gastrointestinal bleeding: A randomized trial.

We aimed toassess the efficacy of lactulose as prophylaxis against hepatic encephalopathy (HE) in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB). We conducted a randomized, double-blinded, placebo-controlled, multicenter study from October 2012 to February 2014. Cirrhotic patients presenting with AUGIB (aged 18-80years, without HE at the time of admission) were enrolled and randomized to receive blinded medications (both physically indistinguishable), labeled "Lactulose A" and "Lactulose B" for 5days along with standard treatment depending on the type of bleeding (variceal and nonvariceal). The primary endpoint was the development of overt HE according to the West-Haven criteria. Modified intention-to-treat analysis was performed. Forty-six patients completed the protocol: Lactulose A (placebo, n= 22) and Lactulose B (lactulose, n= 24). There was no significant difference in baseline characteristics and clinical outcomes between the two groups. Nine (19.6%) patients developed HE: five (22.7%) in the placebo group and four (16.7%) in the lactulose group (p= 0.718). One patient (2.2%) died inlactulose group. All patients tolerated the medication and no significant difference in adverse effects was detected (59.1% inplacebo vs. 50.0% inlactulosegroup, p= 0.536). On multivariate analysis, increased baselineChild-Turcotte-Pugh (CTP) score (odds ratio [OR] 2.176; 95% confidence interval [CI] 1.012-4.681, p= 0.047) and presence of diarrhea (OR 16.261; 95% CI 1.395-189.608, p= 0.026) were independent risk factors for the development of HE. Five-day lactulose is ineffective as prophylaxis against HE in cirrhotic patients with AUGIB. Unnecessarytreatment with laxatives should be avoided in these patients. Clinical trial registry number TCTR20200526003 (retrospectively registered).

Performance of albumin-bilirubin score in prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding

BackgroundHepatic encephalopathy exacerbates the morbidity, delays hospital discharge, and increases the rate of readmissions of cirrhotic patients, particularly those are admitted by acute variceal bleeding. We evaluated the performance of albumin-bilirubin score in prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding, in comparison to Child-Pugh and MELD scores. This prospective cohort study was conducted on 250 cirrhotic patients who were consecutively presented by acute variceal bleeding in the period from January to December 2020 at Tanta university emergency hospital. Albumin-bilirubin, Child-Pugh, and MELD scores were measured at admission, and then all patients were followed up for 4 weeks after endoscopic bleeding control for possible occurrence of hepatic encephalopathyResultsAlbumin-bilirubin, Child-Pugh, and MELD scores had significant performances in prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding; in this regard, albumin-bilirubin score had the highest accuracy (AUC 0.858, CI 0.802-0.914, sig 0.000) followed by Child-Pugh score (AUC 0.654, CI 0.574–0.735, sig 0.001) and then MELD score (AUC 0.602, CI 0.519–0.686, sig 0.031). The cumulative incidence of hepatic encephalopathy in cirrhotic patients with albumin-bilirubin grade 3 was found to be significantly more than that present in albumin-bilirubin grade 2; most of these hepatic encephalopathy cases occurred in the first 2 weeks of follow-up period.ConclusionsAlbumin-bilirubin score has a significant performance in risk prediction of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding better than Child-Pugh and MELD scores. Albumin-bilirubin grades could be used as a risk stratifying tool to triage cirrhotic patients who will benefit from early discharge after bleeding control and those patients who will benefit from prophylactic measures for hepatic encephalopathy.

Evaluation of different diagnostic modalities of minimal hepatic encephalopathy in cirrhotic patients: case-control study.

IntroductionMinimal hepatic encephalopathy (MHE) represents one of the most overlooked complications of liver cirrhosis.Aim of the studyTo compare the utility and efficacy of different MHE diagnostic modalities.Material and methodsThis case-control study was conducted on hepatitis C virus (HCV)-related compensated cirrhotic patients. The Psychometric Hepatic Encephalopathy Score (PHES) was used to assign patients to MHE and controls. All patients were subjected to plasma ammonia, serum 3-nitrotyrosine (3-NT), critical flicker frequency (CFF), and the modified inhibitory control test (ICT).ResultsCFF was significantly lower in the control group (38.5, 40 Hz, p = 0.003). The unweighted lures on ICT were 8.7, 4.9 in MHE and controls (p < 0.001). Moreover, ammonia was higher in the MHE group (89, 61.5 µmol/l, p < 0.001). 3-NT was also higher in the MHE group (31.5, 13.7 nmol/l, p < 0.001) respectively. CFF at cutoff < 39 Hz had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 57.5%, 77.5%, 71.9% and 64.6%, respectively; in modified ICT, at cutoff > 5 unweighted lures the values were 87.5%, 80%, 81.4% and 86.5%, respectively; in ammonia, at cutoff ≥ 76.45 µmol/l the values were 65%, 72.5%, 70.3% and 67.4%, respectively; for 3-NT at cutoff ≥ 14.15 nmol/l the values were 85%, 82.5%, 82.9% and 84.6%, respectively. The accuracy for MHE diagnosis was 67.5%, 83.3%, 68.8%, 83.8% relying on CFF, 3-NT, ammonia, and ICT respectively. On multivariate analysis, CFF < 39 Hz (OR = 10.2, p = 0.04), modified ICT > 5 unweighted lures (OR = 43.2, p = 0.002), and serum 3-NT levels ≥ 14.15 nmol/l (OR = 50.4, p < 0.001) were independent predictors of MHE.Conclusions3-NT and ICT are advantageous to reveal MHE in compensated liver cirrhosis, while CFF can be only used as adjuncts, with humble merits of ammonia.

Assessment of Precipitating Factors and Outcomes of Hepatic Encephalopathy in Cirrhotic Patients

Background: Hepatic encephalopathy (HE) is one of the major complications of liver cirrhosis (LC). It’s defined as a reversible neuropsychiatric event of liver cirrhosis. Up to fifty percent of cirrhotic patients will suffer from at least one attack of HE. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. The current study aimed to assess outcome of hepatic encephalopathy. Patients and methods: Over one year duration, 100 patients with HE were enrolled. All patients were subjected to full history taking and full examination. Patient with central nervous system lesion, metabolic disorders or post-ictal state was excluded. Abdominal ultrasound and ascitic fluid examination were performed in all patients. Patients were followed and their outcome was recorded. Results: Mean age of patients was 53.19 ±3.6 years and the majority of patients were males. Hepatitis C infection was the most frequent cause of LC. The main precipitating factor for HE was infection (29%) followed by hematemesis (24%) and constipation (19%). In 19 (19%) patients, there was evidence of ascitic fluid infection. Out of studied patients; 81 (81%) patients were alive. It was noticed that hematemesis and infection were significantly higher in dead patients. Conclusion: hepatic encephalopathy is a serious event in patients with LC. Major precipitating factors were infection, hematemesis and constipation. Infection and hematemesis are usually associated with poor outcome.

Intractable hepatic encephalopathy in cirrhotic patients: mid-term efficacy of balloon-occluded retrograde portosystemic shunt obliteration.

To evaluate the efficacy and intermediate-term outcome of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hepatic encephalopathy (HE) secondary to portosystemic shunt (PSS) in cirrhotic patients. Institutional review board (IRB) approval was obtained for this study and hospital records of patients who underwent BRTO, from August 2011 to August 2015, were analyzed. Based on the inclusion and exclusion criteria, 39 patients (age, 54.07 ± 9.1years (37-67years); 33 males and 6 females) with cirrhosis and spontaneous PSS were included. Clinical and laboratory parameters and HE grade were evaluated in all patients before and after the procedure. Forty sessions of BRTO were attempted in 39 patients. Follow-up imaging revealed complete obliteration of the treated PSS in all patients with clinical success in 37 patients (94.9%). The 1-, 2-, 3-, 4-, 5-, 6-, and 7-year HE-free survival rates among responders were 91.7%, 91.7%, 88.8%, 85.5%, 80.8%, 80.8%, and 80.8% respectively and overall survival rates were 89.7%, 82.1%, 76.9%, 74.4%, 74.4%, 64.8%, and 64.8% respectively. Logistic regression highlighted Child-Turcotte-Pugh (CTP) score at 6months as a positive predictive factor of HE recurrence with a cutoff of ≥ 9. Five patients (12.8%) had fever and leukocytosis and 1 (2.6%) patient developed spontaneous bacterial peritonitis after the procedure. BRTO is an effective treatment for refractory HE in cirrhotics secondary to large PSS with a few possible complications. • BRTO is an effective and safe treatment for refractory HE, arising from PSS in cirrhotic patients. • Patients with preserved liver function show better outcome and CTP score is the most important predictor of relapse during follow-up.

Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients.

BACKGROUNDLiver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.AIMTo investigate the relationship between the use of proton pump inhibitors (PPIs) and HE in patients with cirrhosis.METHODSThis is a single center, retrospective analysis. Patients were included in the study with an admitting diagnosis of HE. The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria. The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course. Secondary outcomes included rate of infection, gastrointestinal bleeding within the last 12 mo, mean ammonia level, and model for end-stage liver disease scores at admission.RESULTSThe HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group (P = 0.001). The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers (P = 0.046). Twenty-seven (31.8%) patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group (16.7%) (P = 0.138). Finally, 10 (11.8%) patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group (2.8%) (P = 0.220).CONCLUSIONChronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.