Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient's family and significantly affects the patient's quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS. METHODS AND ANALYSIS: PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software. ETHICS AND DISSEMINATION: Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359208.

Preventing Readmissions of Hepatic Encephalopathy: Strategies in the Acute Inpatient, Immediate Postdischarge, and Longitudinal Outpatient Setting.

Hepatic encephalopathy (HE) is a strong predictor of early hospital readmission in patients with cirrhosis. Early hospital readmission increases health care costs and is associated with worse survival. Herein we provide an overview of strategies to prevent hospital readmissions in patients with HE, divided into 3 contexts: (a) acute inpatient, (b) immediate postdischarge, and (c) longitudinal outpatient setting.

Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Myosteatosis in cirrhotic patients has been evaluated in limited studies with conflicting results and no systematic review or meta-analysis have been performed in this setting. METHODS: We searched for all articles published until June 2023 to evaluate the prevalence of myosteatosis in cirrhosis and chronic liver disease. RESULTS: Seventeen studies focused on cirrhosis and five studies in patients with chronic liver disease were included: the overall pooled prevalence of myosteatosis was 46% [95% Confidence Interval (CI) 36-57%] and 33% (95% CI 15-59%), respectively (p = 0.35). Among the studies with cirrhosis, the prevalence of myosteatosis was higher in those using the body mass index-based definition of myosteatosis (56%), than gender-based (36%) or other criteria (21%) (p < 0.01); was higher in women than in men (61% vs 45%), in Child-Pugh class C than A or B (57% vs 49% vs 50%), in non-alcoholic fatty liver disease (NAFLD)- than viral-associated cirrhosis (57% vs 43%), but these differences were not statistically significant (p > 0.05). Cirrhotic patients with myosteatosis, compared to those without myosteatosis, had more frequently a previous history of hepatic encephalopathy (32% vs 15%, p = 0.04), less frequently a previous history of variceal bleeding (46% vs 65%, p < 0.01), were more likely to suffer from diabetes mellitus (27% vs 18%, p < 0.01), while they had higher mortality rates (40% vs 14%, p = 0.02). CONCLUSION: Myosteatosis is highly prevalent in patients with cirrhosis, particularly in those with NAFLD-associated cirrhosis. Myosteatosis is associated with hepatic encephalopathy, while it seems to have a negative impact on the outcome.

Interventional embolisation for patients with cirrhosis and recurrent or persistent hepatic encephalopathy related to spontaneous portosystemic shunts: protocol for a prospective, non-randomised controlled study.

INTRODUCTION: The presence of spontaneous portosystemic shunts (SPSS) has been identified to be associated with hepatic encephalopathy (HE) in patients with cirrhosis. Nevertheless, the role of interventional embolisation in managing such patients remains poorly defined. Consequently, this prospective controlled study aims to assess the efficacy and safety of interventional embolisation as a therapeutic approach for patients with cirrhosis and recurrent or persistent HE related to SPSS. METHODS AND ANALYSIS: Cirrhotic patients diagnosed with recurrent or persistent HE associated with SPSS will be recruited for this study, and assigned to either the interventional embolisation group or the standard medical treatment group. The efficacy endpoints encompass the evaluation of postoperative alleviation of HE symptoms and the incidence of overt HE recurrence during the follow-up period, as well as the duration and frequency of hospitalisations for HE, alterations in liver function and volume, and overall survival. The safety endpoints encompass both immediate and long-term postoperative complications. ETHICS AND DISSEMINATION: This study will be conducted in strict adherence to the principles of good clinical practice and the guidelines outlined in the Declaration of Helsinki. Ethical approval for the trial has been obtained from the Ethics Committee of Mengchao Hepatobiliary Hospital of Fujian Medical University (2023_013_02). Written informed consent will be obtained from all the participants by the treating physician for each patient prior to their enrolment. The documented informed consent forms will be retained as part of the clinical trial records for future reference. The study findings will be disseminated through publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300072189.

Metabolic disorder and functional disturbance in the central executive network in minimal hepatic encephalopathy.

The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach. Dynamic functional connectivity across central executive network was calculated using sliding-window approach. Functional states were estimated by K-means clustering. Right dorsolateral prefrontal cortex metabolite ratios (i.e. glutamate and glutamine complex/total creatine, myo-inositol / total creatine, and choline / total creatine) were determined. Neurocognitive performance was determined by psychometric hepatic encephalopathy scores. Minimal hepatic encephalopathy patients had decreased myo-inositol / total creatine and choline / total creatine and increased glutamate and glutamine complex / total creatine in right dorsolateral prefrontal cortex (all P ≤ 0.020); decreased static functional connectivity between bilateral dorsolateral prefrontal cortex and between right dorsolateral prefrontal cortex and lateral-inferior temporal cortex (P ≤ 0.001); increased frequency and mean dwell time in state-1 (P ≤ 0.001), which exhibited weakest functional connectivity. Central executive network dynamic functional indices were significantly correlated with right dorsolateral prefrontal cortex metabolic indices and psychometric hepatic encephalopathy scores. Right dorsolateral prefrontal cortex myo-inositol / total creatine and mean dwell time in state-1 yielded best potential for diagnosing minimal hepatic encephalopathy. Dynamic functional disturbance in central executive network may contribute to neurocognitive impairment and could be correlated with metabolic disorder.

Impact of nutritional status on the outcome of transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review.

OBJECTIVES: Malnutrition and sarcopenia have been reported to adversely affect the outcome of patients with cirrhosis of the liver. There is an emerging body of evidence suggesting malnutrition and sarcopenia increase the risk of hepatic encephalopathy (HE) and mortality after transjugular intrahepatic portosystemic shunt (TIPS). The current systematic review aims to determine whether the body of evidence supports an association between nutritional status and post-TIPS outcomes in patients with cirrhosis. METHODS: Electronic databases of PubMed, Embase, and Scopus were searched from inception to June 3, 2023, for studies analysing the effect of nutritional status on post-TIPS outcomes in patients with cirrhosis. RESULTS: A total of 22 studies were included in the systemic review. Assessment of sarcopenia was done by skeletal muscle index (SMI) at the L3 level, transversal psoas muscle thickness, psoas muscle density, malnutrition as per ICD, relative sarcopenia with excess adiposity, lipid profile, controlling nutritional status score, body composition analysis, hospital frailty risk score, and visceral and subcutaneous fat area index. Ten out of 12 studies in this systematic review showed a significant association with the incidence of post-TIPS HE. Thirteen out of 14 studies reported that the presence of malnutrition was associated with increased odds of mortality following TIPS. One study reported sarcopenia as an independent predictor of liver failure, and another study reported that Pre-TIPS SMI was an independent predictor of substantial improvement in post-TIPS SMI. CONCLUSIONS: The current systematic review shows that the presence of pre-TIPS malnutrition or sarcopenia is an independent predictor of adverse outcomes after TIPS. Incorporating these parameters into present prediction models can provide additional prognostic information. ADVANCES IN KNOWLEDGE: Nutritional assessment should be part of the evaluation of patients planned for TIPS for prediction of adverse events after the procedure.

Association between sarcopenia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review and meta-analysis.

PURPOSE: The association between the presence of sarcopenia in patients with cirrhosis and the onset of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) is yet to be established. We conducted a systematic review and meta-analysis to provide a thorough summary of the available evidence on this association. METHODS: A thorough search of the literature was performed in the PubMed, EMBASE, and Web of Science databases. The protocol was duly registered on PROSPERO (CRD42023398856). The hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the occurrence of HE after TIPS were extracted from studies comparing cirrhotic patients with and without sarcopenia. These data were then combined using a random-effect model. RESULTS: A total of 1135 patients from seven cohort studies that met our eligibility criteria were included in the meta-analysis. Our findings indicate a significantly higher risk of post-TIPS HE among cirrhotic patients with sarcopenia compared to those without sarcopenia (HR, 2.35; 95% CIs 1.32-4.19; p = 0.004; I2 = 75%). The findings remained consistent across subgroups stratified by liver disease etiology, study location, and severity of hepatic dysfunction. CONCLUSION: The study demonstrated that sarcopenia was strongly linked to an increased likelihood post-TIPS HE among cirrhotic patients.

Short-latency reaction time and accuracy are impaired in patients with cirrhosis: An international multicenter retrospective study.

AIM: The inability to quickly react to an external event can lead to an increased risk for accidents (e.g., falls, car crashes) in patients with cirrhosis. The aim of this study was to determine whether a novel clinically feasible measure of simple reaction time (SRT) and reaction accuracy (RA)-a go/no-go task occurring within 400 ms-could differentiate patients with cirrhosis from controls. METHODS: This retrospective study included 160 patients with cirrhosis and 160 controls assessed between January 2010 and October 2022. SRT and RA were evaluated using a ruler drop paradigm and compared using propensity score matching. Factors distinguishing patients with cirrhosis from controls were assessed using logistic regression and receiver operating characteristics curve (ROC) analyses. RESULTS: Propensity score matching identified 112 participants in each group with comparable baseline characteristics. As compared with controls, patients with cirrhosis exhibited significantly prolonged SRT (200 vs. 174 ms; P < 0.001) and diminished total RA (63% vs. 73%; P < 0.001). After adjustment for confounding factors, SRT and RA independently identified patients with cirrhosis. ROC analyses showed that SRT more effectively identified patients with cirrhosis than did the number-connection test/trail-making test-B (area under the curve, 0.87 vs. 0.60; P < 0.001). CONCLUSIONS: Patients with cirrhosis demonstrated impairments in short-latency cognitive function. Given that SRT and RA are associated with balance, falls, and response to perturbation, these parameters may present a task-specific method to identify patients with cirrhosis at high risk of falls and motor vehicle crashes. Geriatr Gerontol Int 2024; 24: 25-31.

Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. METHODS: Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). RESULTS: A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. CONCLUSIONS: This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival.

Proton Pump Inhibitor Use and Complications of Cirrhosis Are Linked With Distinct Gut Microbial Bacteriophage and Eukaryotic Viral-Like Particle Signatures in Cirrhosis.

INTRODUCTION: Proton pump inhibitors (PPIs) modulate the progression of cirrhosis to hepatic encephalopathy (HE) and can affect the bacterial microbiome. However, the impact of PPI on the virome in cirrhosis using viral-like particle (VLP) analysis is unclear. METHODS: We determined the VLP in the stool microbiome in patients with cirrhosis cross-sectionally (ascites, HE, and PPI use analyzed) who were followed up for 6-month hospitalizations and through 2 clinical trials of PPI withdrawal and initiation. RESULTS: In a cross-sectional study, PPI users had greater ascites prevalence and 6-month hospitalizations, but VLP α diversity was similar. Among phages, PPI users had lower Autographviridae and higher Streptococcus phages and Herelleviridae than nonusers, whereas opposite trends were seen in ascites and HE. Trends of eukaryotic viruses (higher Adenoviridae and lower Virgaviridae/Smacoviridae) were similar for PPI, HE, and ascites. Twenty-one percent were hospitalized, mostly due to HE. α Diversity was similar in the hospitalized/nonhospitalized/not groups. Higher Gokushovirinae and lower crAssphages were related to hospitalizations such as HE-related cross-sectional VLP changes. As part of the clinical trial, PPIs were added and withdrawn in 2 different decompensated groups over 14 days. No changes in α diversity were observed. Withdrawal reduced crAssphages, and initiation reduced Gokushovirinae and Bacteroides phages. DISCUSSION: In cirrhosis, PPI use has a gut microbial VLP phage signature that is different from that in HE and ascites, and VLP changes are linked with hospitalizations over 6 months, independent of clinical biomarkers. Eukaryotic viral patterns were consistent across PPI use, HE, and ascites, indicating a relationship with the progression of cirrhosis. PPIs alone showed modest VLP changes with withdrawal or initiation. Distinct phage and eukaryotic viral patterns are associated with the use of PPIs in cirrhosis.

Comparative efficacy of early TIPS, Non-early TIPS, and Standard treatment in patients with cirrhosis and acute variceal bleeding: a network meta-analysis.

BACKGROUND: Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. MATERIALS AND METHODS: The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. RESULTS: Twenty-four RCTs (1894 patients) were included in the review. Compared with standard treatment, early TIPS [odds ratio (OR), 0.53; 95% credible interval (Cr), 0.30-0.94; surface under the cumulative ranking curve (SUCRA), 98.3] had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI, 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions. CONCLUSION: Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.

Predictors of clinical trajectories of patients with acutely decompensated cirrhosis. An external validation of the PREDICT study.

BACKGROUND AND AIMS: The PREDICT study recently showed that acutely decompensated (AD) patients with cirrhosis can present three different clinical phenotypes in the 90 days after admission: (1) pre-ACLF, developing acute-on-chronic liver failure (ACLF); (2) unstable decompensated cirrhosis (UDC), being re-admitted for AD without ACLF and (3) stable decompensated cirrhosis (SDC), not presenting readmission or ACLF. This study aimed to externally validate the existence of these three distinct trajectories and to identify predictors for the occurrence of each trajectory. METHODS: Baseline data, 3-month ACLF and readmission incidence and 1-year survival were analysed in a prospective cohort of patients admitted for AD. A multinomial multivariable model was used to evaluate the association between baseline features and clinical trajectories. RESULTS: Of the 311 patients enrolled, 55% met the criteria for SDC, 18% for UDC and 27% for pre-ACLF, presenting a significantly different 1-year mortality: pre-ACLF 65%, UDC 46%, SDC 21% (p < .001). The presence of hepatic encephalopathy (HE) was associated with UDC (p = .043), while the absence of ascites to SDC (p = .017). Among laboratory parameters, an increase in MELD-Na (p = .001) and C-reactive protein (p = .009) and a decrease in haemoglobin (p = .004) and albumin (p = .008) levels were associated with pre-ACLF. CONCLUSION: The present study confirms that AD patients have three different clinical trajectories with different mortality rates. Besides the severity of cirrhosis, the association with C-reactive protein supports the predominant role of systemic inflammation in ACLF pathophysiology. Finally, HE is associated with the UDC phenotype highlighting the need for better management of this complication after discharge.

Meld-sarcopenia score and skeletal muscle density predicts short-term readmission of patients with hepatic encephalopathy.

PURPOSE: To investigate whether the quality of skeletal muscle mass could predict short-term readmission in patients with hepatic encephalopathy (HE). METHOD: Patients with HE were enrolled from 2018 to 2022. Sarcopenia and myosteatosis were defined using the L3 skeletal muscle index (SMI) and skeletal muscle density (SMD) obtained from CT imaging. MELD-Sarcopenia score was calculated. Multivariable analysis and multiple linear regression were applied to identify predictors of 30-day readmission and length of hospitalization. RESULTS: 123 patients with HE were included. 55 (44.7%) and 87 (70.7%) patients were identified with sarcopenia and myosteatosis, respectively. Patients with sarcopenia exhibited a higher prevalence of myosteatosis, lower SMI and SMD (p < 0.05). Patients with myosteatosis were older, had a lower body mass index, a higher neutrophil-to-lymphocyte ratio and MELD-sarcopenia scores (p < 0.05). 10 (8.1%) patients were readmitted within 30 days. The readmitted group had a higher MELD-sarcopenia score (25.0 ± 6.6 vs. 19.5 ± 7.8, p = 0.034) and lower L3 SMD (28.3 ± 5.9 vs. 33.8 ± 6.9, p = 0.015). In the multivariable analysis, MELD-sarcopenia score (95% CI 1.388 [1.074-1.793], p = 0.012) and SMD (95% CI 0.778 [0.610-0.991], p = 0.042) were found to be significantly associated with the 30-day readmission of patients with HE. Age (p = 0.028), alcohol liver disease (p = 0.025), and hypertension (p = 0.003) were associated with the length of hospitalization for patients with HE. CONCLUSIONS: The MELD-sarcopenia score and SMD were identified as predictive factors for short-term readmission in patients diagnosed as HE.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Evaluating clinical outcomes and prognosis in patients with cirrhosis and portal hypertension: a retrospective observational cohort study.

OBJECTIVE: Cirrhosis describes the end-stage of chronic liver disease. Irreversible changes in the liver cause portal hypertension, which can progress to serious complications and death. Only a few studies with small sample sizes have investigated the prognosis of cirrhosis with portal hypertension. We used electronic healthcare records to examine liver-related outcomes in patients with diagnosed/suspected portal hypertension. DESIGN: This retrospective observational cohort study used secondary health data between 1 January 2017 and 3 December 2020 from the TriNetX Network, a federated electronic healthcare records platform. Three patient groups with cirrhosis and diagnosed/suspected portal hypertension were identified ('most severe', 'moderate severity' and 'least severe'). Outcomes studied individually and as a composite were variceal haemorrhage, hepatic encephalopathy, complications of ascites and recorded mortality up to 24 months. RESULTS: There were 13 444, 23 299, and 23 836 patients in the most severe, moderate severity and least severe groups, respectively. Mean age was similar across groups; most participants were white. The most common individual outcomes at 24 months were variceal haemorrhage in the most severe group, recorded mortality and hepatic encephalopathy in the moderate severity group, and recorded mortality in the least severe group. Recorded mortality rate was similar across groups. For the composite outcome, cumulative incidence was 59% in the most severe group at 6 months. Alcohol-associated liver disease and metabolic-associated steatohepatitis were significantly associated with the composite outcome across groups. CONCLUSION: Our analysis of a large dataset from electronic healthcare records illustrates the poor prognosis of patients with diagnosed/suspected portal hypertension.

Quantitative susceptibility mapping in rats with minimal hepatic encephalopathy: Does iron overload aggravate cognitive impairment by promoting neuroinflammation?

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.

[Update points for the 2022 edition of the European Association for the Study of Liver Diseases Clinical Practice Guidelines for the Management of Hepatic Encephalopathy and comparison with China's 2018 edition guidelines].

The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.

MEFIB-Index and MAST-Score in the assessment of hepatic decompensation in metabolic dysfunction-associated steatosis liver disease-Individual participant data meta-analyses.

BACKGROUND: There are limited data regarding the longitudinal association between MEFIB-Index (MRE combined with FIB-4) versus MAST-Score (MRI-aspartate aminotransferase) and hepatic decompensation. AIM: To examine the longitudinal association between MEFIB-Index versus MAST-Score in predicting hepatic decompensation in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI-PDFF and were followed for hepatic decompensation. Cox-proportional hazard analyses were used to assess the association between MEFIB-Index versus MAST-Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment. RESULTS: This meta-analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB-Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST-Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow-up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB-Index [HR = 49.22 (95% CI: 6.23-388.64, p < 0.001)] and a positive MAST-Score [HR = 3.86 (95% CI: 1.46-10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB-Index (c-statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST-Score (c-statistic: 0.81, SE = 0.03) (p < 0.0001) in predicting hepatic decompensation. CONCLUSION: A combination of MRI-based biomarker and blood tests, MEFIB-Index and MAST-Score can predict the risk of hepatic decompensation in patients with MASLD.

Prevalence of delirium in gastroenterology/hepatology units: A cross-sectional study.

Prevalence rates of delirium amount to 22.0% within acute-care settings. In contrast, 30-40% of patients with liver cirrhosis may develop hepatic encephalopathy, a condition that has been classified as a syndrome of delirium, based on recent pathophysiology findings. However, the prevalence of delirium in gastroenterology and hepatology units is unknown.The aims of the study were (i) to identify delirium prevalence rates in inpatients of gastroenterology/hepatology wards, (ii) to analyze the delirium motor subtype, and (iii) to assess associations between delirium and patient characteristics.In this monocentric, cross-sectional, epidemiological study, point prevalence was assessed at six time points in three gastroenterology/hepatology units within a German university hospital. Delirium was assessed using the 4 'As' Test (4AT) and delirium subtype by the delirium motor subtype scale. Patient characteristics were collected from patient charts.The sample consisted of 188 patients, aged 18 to 98 years (mean age 64, n=110 male). Of them, 18.1% of patients showed delirium symptoms (61.8% hypoactive, 29.4% mixed, and 8.8% hyperactive). For the participants aged ≥65 years (n=96), prevalence of delirium amounted to 26.0%. Significant associations were observed between delirium and the following characteristics: age (p=0.001), length of hospital stay until assessment (p=0.043), cerebrovascular disease (p=0.002), dementia (p=0.010), diabetes mellitus with chronic complications (p=0.012), and gender (nonsignificant trend, p=0.050), while no association was detected between moderate or severe liver disease and delirium (p=0.414).In conclusion, overall prevalence rates of delirium were rather low and did not increase in patients with liver disease.