Hepatic Encephalopathy In Patients Research Articles

History of depression is associated with higher prevalence of hepatic encephalopathy in patients with advanced liver disease

Introduction: Depression and hepatic encephalopathy are common in patients with advanced liver disease. Although these are distinct entities, they share several clinical features. In this analysis, we evaluated whether having a history of depression was associated with developing hepatic encephalopathy in patients with advanced liver disease Methods: We performed a retrospective cohort study of patients with cirrhosis referred for liver transplant. Patients were categorized into one of two groups: “history of depression” or “no history of depression.” Multivariable logistic regression was used to evaluate history of depression as a potential independent predictor of hepatic encephalopathy Results: A total of 447 patients were included, of which 158 (35%) had a history of depression and 233 (52%) had experienced hepatic encephalopathy. Hepatic encephalopathy was more common in patients with a history of depression (63% vs. 46%, p<0.01). On multivariate analyses, depression history was independently associated with hepatic encephalopathy (aOR 2.3, 95% CI 1.4-3.6), along with alcohol associated cirrhosis (aOR 2.0, 95% CI 1.3-3.2), history of ascites (aOR 3.5, 95% CI 2.1-5.9) and presence of a trans-jugular intra-hepatic shunt (aOR 9.2, 95% CI 2.6-32.6). The relationship between history of depression and hepatic encephalopathy remained significant in a subgroup of patients with alcohol associated liver disease (p=0.04). Among those with a history of depression, SNRI prescription was more common in the hepatic encephalopathy group (14% vs. 3%), and SNRI prescription was as an independent predictor of hepatic encephalopathy in the multivariable model (OR 4.8, 95% CI 1.0, 24.6) Conclusion: Patients with a history of depression were significantly more likely to experience hepatic encephalopathy. Patients with cirrhosis who have a history of depression should be closely monitored for the development of hepatic encephalopathy. Further research is needed to understand the nuances of this relationship and whether the use of certain psychiatric medications may modify the relationship between depression and hepatic encephalopathy.

Nutritional counseling improves mortality and prevents hepatic encephalopathy in patients with alcohol-associated liver disease.

Nutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol-associated liver disease. In this retrospective cohort study, we included 211 patients with alcohol-associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all-cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders. Among the patients (median age 67years; 88% men; and median Model for End-Stage Liver Disease score, 9), 86 (39%) were in the high-frequency (≥2) nutritional counseling group. The high-frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5years than the low-frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36-0.63) and overt HE (HR 0.64; 95% CI 0.42-0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19-0.59) and overt HE (HR 0.31; 95% CI 0.11-0.87). Nutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol-associated liver disease, thereby proving essential for the management of these patients.

Proton pump inhibitor use and risk of hepatic encephalopathy: a multicenter study

Background & AimsData on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicenter studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). MethodsData from patients with cirrhosis recruited at seven centers across Europe and the US were analyzed. MHE was defined by the Psychometric Hepatic Encephalopathy Score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation (LTx). Results1160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of the patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/LTx. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. ConclusionsPPI use is not associated with a higher risk of HE in patients with liver cirrhosis. On the basis of these findings, a prescription should currently not be prohibited in case of a generally accepted indication. Impact and implicationsData on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with liver cirrhosis. On the basis of these findings, a prescription of a PPI by a physician should currently not be prohibited in case of a generally accepted indication.

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

IntroductionHepatic 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,...

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

EncephalApp Stroop Test as a Screening Tool for the Detection of Minimal Hepatic Encephalopathy in Patients with Cirrhosis—Single-Center Experience

Background: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy. One of the neuropsychological tests that detects MHE is the Stroop test (via EncephalApp). The aim was to evaluate the Stroop test for the screening and diagnosis of MHE. Methods: This prospective case–control study was performed at the Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, and included patients with cirrhosis and MHE and healthy controls. In all patients, the presence of MHE was confirmed using the animal naming test. The Stroop test was performed on each participant, and the results were compared between the two groups. The test has two components, the “OFF” and “ON” states. Results: A total of 111 participants were included. The median OFF time did not differ between the two groups, 106.3 and 91.4, p &gt; 0.05. However, in patients with MHE, the median values of ON time and total time were significantly higher, with 122.3 vs. 105.3 and 228.0 vs. 195.6, respectively, p &lt; 0.05. Statistical significance between patients and controls in examined parameters was detected in younger participants and the group with higher educational levels. Conclusions: The Stroop test displayed limited sensitivity in Serbian patients. Age and education affect time measurements and test performance.

Neurofilament light chain but not glial fibrillary acidic protein is a potential biomarker of overt hepatic encephalopathy in patients with cirrhosis

Introduction and ObjectivesHepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). Materials and MethodsWe included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. ResultsICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). ConclusionsPlasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.

Association of low serum 25-Hydroxy vitamin D [25(OH) d] with hepatic encephalopathy in patients with decompensated liver cirrhosis

Background and study aimsThe mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. Patients and methodsA total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). ResultsThe mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r = − 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). ConclusionA significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

Precipitating Factors and Outcomes of Hepatic Encephalopathy in Patients with Chronic Liver Disease

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric condition that significantly impacts patients with chronic liver disease (CLD), leading to hospital admissions and contributing to the economic burden on healthcare systems. The condition's pathogenesis involves various precipitating factors, yet its management remains challenging due to the multifaceted nature of its presentation. Objective: This study aims to identify the precipitating factors of HE in patients with CLD, assess the severity and outcomes of HE, and evaluate the correlation between precipitating factors and the severity and outcomes of HE in patients admitted to PNS Shifa Hospital, Karachi, Pakistan. Methods: A descriptive cross-sectional study was conducted over six months, from February 2022 to July 2022, at the Department of Medicine, PNS Shifa, Karachi. A total of 78 patients meeting the inclusion criteria were enrolled through convenience sampling. Informed consent was obtained from each participant. The severity of liver disease was assessed using the Child-Pugh Classification, and the presence and grade of HE were determined using the West Haven criteria. Precipitating factors of HE were evaluated, and patients were followed until discharge to assess the length of hospital stay and in-hospital mortality. Data were analyzed using SPSS version 25, focusing on descriptive and inferential statistics. Results: The mean age of the participants was 48.77 ± 13.37 years, with the duration of CLD averaging 3.19 ± 1.45 years. Hospital stays ranged from 1 to 7 days, with a median of 5.0 days. Child-Pugh classification revealed 35.9% of patients in Class A, 33.3% in Class B, and 30.8% in Class C. HE grades were distributed as follows: Grade I in 48.7%, Grade II in 24.4%, Grade III in 15.4%, and Grade IV in 11.5% of patients. In-hospital mortality was observed in 15.4% of cases. The most common precipitating factors identified were constipation (59.0%), followed by hypoglycemia (52.6%), and recent excessive paracentesis (48.7%). Conclusion: The study underscores the importance of identifying and managing precipitating factors of HE in patients with CLD to mitigate the severity of HE and improve patient outcomes. Constipation, hypoglycemia, and recent excessive paracentesis were the most prevalent precipitating factors, suggesting targeted interventions in these areas could reduce the incidence and severity of HE.

Erratum: Predicting hepatic encephalopathy in patients with cirrhosis: A UK-population based study and validation of risk scores.

Erratum: Predicting hepatic encephalopathy in patients with cirrhosis: A UK-population based study and validation of risk scores.

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.

Improved cognition after rifaximin treatment is associated with changes in intra- and inter-brain network functional connectivity

BackgroundRifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well.MethodsTwenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed.ResultsAfter rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers.ConclusionsThere was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.

The assessment and management of cirrhotic patients with encephalopathy.

Hepatic encephalopathy (HE) is a debilitating complication associated with both acute and chronic liver injury. It is associated with a greater risk of death than any other significant hepatic decompensation event. It manifests as a wide spectrum of neuropsychological abnormalities ranging from subtle impairments in higher cognitive function, to confusion and coma. The pathophysiological role of ammonia in the development of HE is well known, but there is increasing recognition that the gut microbiome, gut-derived systemic inflammation and development of infection can serve as drivers of HE in patients with cirrhosis. The development of HE portents to the severity of cirrhosis and the prognosis is poor without liver transplantation. A referral for liver transplantation should therefore be considered early in those who are eligible. This review covers the pragmatic assessment of HE in patients with cirrhosis, as well as the current evidence base for the best practice management of HE in such patients.

Prophylactic Lactulose Therapy in Patients with Cirrhosis and Upper Gastrointestinal Bleeding: A Meta-analysis of Randomized Trials.

Lactulose is the first-line drug for both treatment and secondary prophylaxis for overt hepatic encephalopathy (HE). The use of lactulose for the primary prophylaxis of HE in patients with cirrhosis and acute upper gastrointestinal bleeding (AUGIB) has been debated. Hence, we conducted this meta-analysis to assess the role of lactulose in HE prophylaxis in patients with cirrhosis and AUGIB. A comprehensive search of literature from inception to December 2022 was performed of three databases for randomized studies comparing lactulose and placebo in patients with cirrhosis and AUGIB. Risk ratios (RR) with 95% confidence intervals were calculated for all the dichotomous outcomes. A total of five studies were included in the final analysis, out of which three studies had a low risk of bias, and two had a moderate risk of bias. Lactulose therapy was associated with a significantly lower risk of OHE compared to placebo, with a RR of 0.38 (0.23-0.62) and a number needed to treat of 6. There was no difference in the risk of mortality between the groups, with a RR of 0.71 (0.29-1.76). The pooled incidence rates of overall adverse events (AEs) and diarrhea with the use of lactulose therapy were 53.2% (42.2- 64.2) and 34.7% (17.7-51.7), but a majority did not require drug discontinuation. The certainty of the evidence was moderate to low. Prophylactic lactulose reduces the incidence of HE after AUGIB but has no effect on mortality. Diarrhea and abdominal discomfort are common AEs but do not need drug discontinuation.

Fecal microbiota transplant is associated with lower risk of mortality, hepatic encephalopathy, ascites, and infection patients with severe alcohol-associated hepatitis: A systematic review and meta-analysis

Fecal microbiota transplant is associated with lower risk of mortality, hepatic encephalopathy, ascites, and infection patients with severe alcohol-associated hepatitis: A systematic review and meta-analysis

Higher scores in the Clinical Frailty Scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis

BackgroundFrailty increases the vulnerability to internal and external stressors and may therefore be an indicator of a higher frequency of cirrhosis complications. We aimed to investigate the association of the Clinical Frailty Scale (CFS) with covert (CHE) and overt HE (OHE) development in patients with cirrhosis. MethodsThis study analyzed data of 228 patients with cirrhosis. Frailty was assessed using CFS. Patients were examined for the presence of CHE (using PHES) at study inclusion and followed for OHE. ResultsMedian CFS was 3 and 26 (11 %) patients were at least pre-frail (CFS>3). In multivariable logistic regression analysis in patients without a history of OHE (n = 195), a higher CFS was associated with the presence of CHE at baseline (OR 1.6, p = 0.039). During follow-up, 42 (18 %) patients developed an episode of OHE. In multivariable competing risk regression analyses, a higher CFS was independently associated with the development of an OHE episode in the total cohort (sHR 1.97, p < 0.001) and in the subcohort of patients without a history of OHE (sHR 1.88, p = 0.008). ConclusionCFS appears to be a reliable tool to identify patients at higher risk of HE in whom intensified monitoring and treatment may be justified.

Establishment and validation of a nomogram model for riskprediction of hepatic encephalopathy: a retrospective analysis

To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63–0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541–0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer–Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ2 = 1.237587, P = 0.998, and for the validation set, χ2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.

Predicting hepatic encephalopathy in patients with cirrhosis: A UK population-based study and validation of risk scores.

HE is a common neurologic complication in cirrhosis associated with substantial disease and economic burden. HE symptoms are nonspecific and there are limited ways of identifying patients with cirrhosis at high risk of later developing HE. A risk score was previously developed to identify patients at risk of developing HE in a predominately male US cohort. Here, we evaluated the performance of the HE risk scores in a UK cohort study. Health care records from Clinical Practice Research Datalink and linked Hospital Episode Statistics were used to select patients with cirrhosis who were diagnosed with HE, confirmed by a diagnosis code for HE or a rifaximin-α prescription. The index date was the date of incident cirrhosis. The study period was from January 2003 to June 2019. A total of 40,809 patients with cirrhosis were selected in the UK cohort, of whom 59% were male. A total of 1561 patients were diagnosed with HE. Applying the UK cohort to the baseline sensitivity risk cutoff (≥-11) from the US cohort provided a sensitivity of 92% and a negative predictive value of 99%. Within a longitudinal model, applying a sensitivity cutoff of ≥-3 to this cohort gave a sensitivity of 89% and a negative predictive value of 99%. Using data from the UK, the previously developed HE risk scores were found to be reliable for selecting those most likely to progress to HE in patients with liver cirrhosis. Despite the HE risk scores originally being estimated using the data from a predominately male US cohort, the scores were validated and found to be generalizable to female patients.

Prevalence and Characteristics of Covert/Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Covert/minimal hepatic encephalopathy (C/MHE) is the mildest form of hepatic encephalopathy (HE), but it is closely related to the quality of life and prognosis of patients with cirrhosis. Currently, the epidemiological data of C/MHE have not been well described. We searched the PubMed, Embase, and Cochrane Library databases for relevant articles. We performed a random-effects meta-analysis of proportions to estimate the pooled prevalence of C/MHE in patients with cirrhosis. We also examined potential risk factors for C/MHE by comparing characteristics of patients with and without C/MHE. Finally, a total of 101 studies were included. The prevalence of C/MHE was 40.9% (95% confidence interval, 38.3%-43.5%) among patients with cirrhosis worldwide. The pooled C/MHE prevalence was 39.9% (95% confidence interval 36.7%-43.1%) based on studies using the psychometric HE score as a diagnostic tool. Meta-regression models showed that geographic region, sample size, mean age, sex ratio, and Child-Pugh classification were influencing factors for the heterogeneity of C/MHE prevalence. The presence of C/MHE was found to be associated with various factors including age, level of education, alcoholic etiology, Child-Pugh classification, MELD score, history of overt HE, presence of other complications, and laboratory tests related to impaired liver function. This study reports detailed data on the prevalence of C/MHE as well as clinical features associated with C/MHE, suggesting that C/MHE is one of the most common complications of liver cirrhosis.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.