Development Of Overt Hepatic Encephalopathy Research Articles

Serum zinc levels as predictors of covert hepatic encephalopathy in patients with liver cirrhosis.

Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions. This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated. CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211days, OHE developed in 18 patients (14.3%). The administration of more than 20mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207). Cirrhotic patients with serum zinc levels below 60µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20mg or more of furosemide.

Reduced risk of overt hepatic encephalopathy and death after transjugular intrahepatic portosystemic shunt in patients with hepatic venovenous communications

PurposeHepatic venovenous communications (HVVC) is detectable in more than one-third of cirrhotic patients, where portal hypertension (PHT) tends to present more severely. We aimed to explore the prognostic implications of HVVC in patients with sinusoidal PHT treated by transjugular intrahepatic portosystemic shunt (TIPS). MethodThe multicenter data of patients (2020–2022) undergoing balloon-occluded hepatic venography during TIPS were retrospectively analyzed. Pre-TIPS total bile acids (TBA) levels in portal, hepatic and peripheral veins were compared between groups. The primary endpoint was the development of overt hepatic encephalopathy (HE) within one year after TIPS. Results183 patients were eligible and classified by the presence (n = 69, 37.7 %) or absence (n = 114, 62.3 %) of HVVC. The agreement between wedged hepatic venous pressure and portal venous pressure was poor in HVVC group (intraclass correlation coefficients [ICC]: 0.141, difference: 13.4 mmHg, p < 0.001), but almost perfect in non-HVVC group (ICC: 0.877, difference: 0.4 mmHg, p = 0.152). At baseline, patients with HVVC had lower Model for end-stage liver disease scores (p < 0.001), blood ammonia levels (p < 0.001), TBA concentrations in the hepatic (p = 0.011) and peripheral veins (p = 0.049) rather than in the portal veins (p = 0.516), and a higher portosystemic pressure gradient (p = 0.035), suggesting more effective intrahepatic perfusion in this group. Within 1-year post-TIPS, HVVC group had a lower incidence of overt HE (11.7 % vs. 30.5 %, p = 0.004, HR: 0.34, 95 % CI: 0.16–0.74, absolute risk difference [ARD]: −17.4) and an improved liver transplantation-free survival rate (97.1 % vs. 86.8 %, p = 0.021, HR: 0.16, 95 % CI: 0.05–0.91, ARD: −10.3). ConclusionsFor patients with sinusoidal PHT treated by TIPS, the presence of HVVC was associated with a reduced risk of overt HE and a potential survival benefit.

Proton pump inhibitor use and risk of hepatic encephalopathy: A multicentre 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.

Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis.

There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality ofHE. We evaluated the outcomes by various parameters such as thequality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results alsodemonstrated a significant reduction in ammonia betweenL-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.

QuickStroop Predicts Time to Development of Overt Hepatic Encephalopathy and Related Hospitalizations in Patients With Cirrhosis

Cirrhosis-related neurocognitive impairment caused by covert or minimal hepatic encephalopathy (CHE) affects psychosocial function, increases risk of overt hepatic encephalopathy (OHE) development, and worsens survival.1,2 However, detection in clinical practice is challenging.2 One modality used for screening and prediction of outcomes related to cirrhosis is the EncephalApp Stroop, but it can require up to 10 minutes. Furthermore, the assessment comprises of distinct stages of difficulty, with an easier "Off" stage and a more challenging "On" stage.3 To alleviate these concerns, QuickStroop, which takes <1 minute, was developed. This uses only the first 2 runs of the Off stage of the EncephalApp Stroop, where number signs presented in red, green, or blue need to be matched quickly to their respective colors.4 A prior study showed these versions were comparable cross-sectionally to diagnose CHE.4 However, the utility of QuickStroop to predict cirrhosis-related outcomes is unclear.5-7 Our aim was to determine the ability of QuickStroop to determine time to development of OHE and OHE-related hospitalizations, all-cause hospitalizations, and death in outpatients with cirrhosis.

P29 Development of Overt Hepatic Encephalopathy Is Associated With an Abruptly Increased Risk of Death in Patients Hospitalized With an Acute Decompensation or Acute-On-Chronic Liver Failure

P29 Development of Overt Hepatic Encephalopathy Is Associated With an Abruptly Increased Risk of Death in Patients Hospitalized With an Acute Decompensation or Acute-On-Chronic Liver Failure

Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis

Neuropsychological and psychophysical tests are recommended to assess the risk of overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. In this study, we aimed to determine the role of neuropsychological or psychophysical tests and ammonia, and to develop a model (AMMON-OHE) to stratify the risk of subsequent OHE development in outpatients with cirrhosis. This observational, prospective study included 426 outpatients without previous OHE from three liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk and random survival forest analyses were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units. Significant differences were found in time-to-OHE (log-rank p <0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (hazard ratio 4.4; 95% CI 2.4-8.1; p <0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor of the development of OHE (hazard ratio 1.4; 95% CI 1.1-1.9; p= 0.015). The AMMON-OHE model (sex, diabetes, albumin, creatinine and AMM-ULN) showed a C-index of 0.844 and 0.728 for the prediction of a first episode of OHE in two external validation cohorts. In this study, we developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at the highest risk of developing a first episode of OHE. In this study, we aimed to develop a model to predict which patients with cirrhosis are at risk of developing overt hepatic encephalopathy (OHE). Using data from three units and including 426 outpatients with cirrhosis, we developed the AMMON-OHE model - comprising sex, diabetes, albumin, creatinine and ammonia levels - which demonstrated good predictive ability. The AMMON-OHE model performs better than PHES and CFF to predict the first episode of OHE in outpatients with cirrhosis. This model was validated in 267 and 381 patients from two independent liver units. The AMMON-OHE model is available online for clinical use.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt.

Skeletal muscle abnormalities, such as muscle mass depletion (sarcopenia) and fatty infiltration of the muscle (myosteatosis), are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt (TIPS). To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy (HE) and mortality after TIPS. The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved. The transversal psoas muscle thickness (TPMT) and psoas muscle attenuation (PMA) measured from the unenhanced abdominal computed tomography (CT) at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis, respectively. The area under curve (AUC) was used to evaluate the discriminative power of TPMT, PMA, and relevant clinical parameters. Fur-thermore, log-rank test was performed to compare the incidence of overt HE and survival between the different groups, and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models. A total of 108 patients were collected. Among these patients, 45.4% of patients developed overt HE after TIPS treatment. Furthermore, 32.4% and 28.7% of these patients were identified to have myosteatosis and sarcopenia, respectively. Myosteatosis (51.0% vs 16.9%, P < 0.001) and sarcopenia (40.8 vs 18.6%, P = 0.011) were found to be more frequent in patients with overt HE, when compared to patients without overt HE. The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE (AUC = 0.713 and 0.778, respectively) was higher when compared to the neutrophil lymphocyte ratio (AUC = 0.636). The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis, followed by patients with myosteatosis or sarcopenia, while this was the lowest in patients without sarcopenia and myosteatosis. In addition, sarcopenia and myosteatosis were inde-pendently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients. CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.

Effect of Selenium Deficiency on the Development of Overt Hepatic Encephalopathy in Patients with Chronic Liver Disease.

Selenium is an essential trace element to maintain good health. This retrospective study investigated the prevalence of selenium deficiency and its effect on overt hepatic encephalopathy (OHE) in patients with chronic liver disease (CLD). Patients who underwent serum selenium level measurement between January 2021 and April 2022 were enrolled. The factors associated with selenium deficiency (≤10 µg/dL) and the association between selenium deficiency and OHE were analyzed. Among 98 eligible patients, 24% were observed to have selenium deficiency, with a median serum selenium level of 11.8 µg/dL. The serum selenium levels were significantly lower in patients with cirrhosis than in those with chronic hepatitis (10.9 µg/dL vs. 12.4 µg/dL; p = 0.03). The serum selenium levels were negatively correlated with mac-2 binding protein glycan isomer, the FIB-4 index, albumin-bilirubin (ALBI) score, and Child-Pugh score. The ALBI score remained significantly associated with selenium deficiency (odds ratio, 3.23; 95% confidence interval [CI], 1.56-6.67). During a median follow-up period of 2.9 months, nine patients experienced OHE. Selenium deficiency was associated with OHE (hazard ratio, 12.75; 95% CI, 2.54-70.22). Selenium deficiency is highly prevalent in patients with CLD and is associated with an increased risk of OHE development.

Handgrip strength stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis.

Handgrip strength (HGS) is a simple and convenient method to assess nutrition status in patients with cirrhosis. This retrospective study aimed to investigate the utility of HGS for predicting patients with covert hepatic encephalopathy (CHE) and patients at high risk of overt hepatic encephalopathy (OHE). We reviewed 963 patients with cirrhosis and consequently enrolled eligible 270 patients. HGS was measured using a digital grip dynamometer. CHE was diagnosed using a computer-aided neuropsychiatric test. Factors associated with CHE were estimated using the logistic regression model. Predictors associated with OHE occurrence were analyzed using the Fine-Gray competing risk regression model. Of the 270 eligible patients, reduced HGS was observed in 102 (38%), reduced muscle mass in 107 (40%), and CHE in 53 (20%). Multivariate analysis showed that serum ammonia levels (odds ratio [OR], 2.23; 95% CI, 1.14-4.36; P = 0.014) and reduced HGS (OR, 3.68; 95% CI, 1.93-7.03; P < 0.001) were independently associated with CHE. During the median follow-up period of 24.5 months, 43 (16%) patients experienced OHE. After adjusting for possible confounding factors, multivariate analysis showed that reduced HGS (subdistribution hazard ratio, 2.36; 95% CI, 1.27-4.38; P = 0.007) was a significant predictor in the development of OHE. Patients with reduced HGS had a higher prevalence of CHE and a higher risk for OHE occurrence than those with normal HGS. The measurement of HGS could be a simple bedside modality to stratify the patients' risk for CHE and OHE.

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).

Zinc deficiency predicts overt hepatic encephalopathy and mortality in liver cirrhosis patients with minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) is associated with poor outcomes and the development of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis (LC). Zinc plays a key role in the detoxification of ammonia, a risk factor of hepatic encephalopathy. This study aimed to investigate whether zinc deficiency predicts OHE occurrence and mortality in LC patients with MHE. This retrospective study included 100 LC patients with MHE. MHE was diagnosed using a computer-aided neuropsychiatric test. Predictors associated with the development of OHE were analyzed using the Fine-Gray competing risk regression model. Cox proportional hazards regression analysis was carried out to evaluate the risk factors of mortality. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. Of the 100 LC patients with MHE, 41% had zinc deficiency (<60μg/dl). Zinc deficiency was observed more frequently in the patients with reduced liver function reserve. During the median follow-up period of 9.9months, 16% of the patients with MHE developed OHE. The patients with zinc deficiency had a higher risk of OHE than those without zinc deficiency (p=0.03). Zinc deficiency was also associated with poor survival (p=0.004). Multivariate analyses showed that zinc predicts the development of OHE (subdistribution hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.92-0.99; p=0.008) and mortality (HR, 0.96; 95% CI, 0.93-0.99; p=0.02), independently of liver function reserves. Zinc deficiency is likely to be a predictor of both OHE development and mortality in LC patients with MHE.

Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial)

IntroductionCirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common...

Covert hepatic encephalopathy and spontaneous portosystemic shunts increase the risk of developing overt hepatic encephalopathy.

The aim of the study was to evaluate the presence of covert hepatic encephalopathy (cHE) and its characteristics according to the presence of spontaneous portosystemic shunts (SPSS) and their influence on the development of overt hepatic encephalopathy. Secondary analysis of a multicentre study, which evaluated the association between SPSS and complications of cirrhosis. The present study population includes those patients who also underwent cHE diagnostic evaluation. Presence of SPSS was evaluated by cross-sectional imaging and quantified by total SPSS-area. Logistic and Cox-regression competing risk analyses were performed. About 65 patients were included of age 58 (IQR 50-66), MELD 15 (IQR 10-20), with alcoholic liver disease 63%. Thirty-two patients (49%) had cHE, had higher MELD [16 (IQR 12-24) vs 13 (IQR 9-17), P=.027], a greater proportion of SPSS [n=18 (56%) vs n=8 (24%); P=.008] and a higher total cross-sectional SPSS-area [28.3 (0-94.2) vs 0 (0-14.1); P=.005]. On multivariate analysis MELD [OR 1.11 (95% CI 1.01-1.21)] and presence of SPSS [OR 3.95 (95% CI 1.22-12.80)] were independently associated to cHE at baseline. During follow-up cHE was an independent predictor of oHE [cHE: HR 6.93 (95% CI 2.64-18.20). The effect of cHE on the development of oHE was greater in patients with SPSS [only cHE: HR 5.66 (95% CI 1.82-17.62), cHE and SPSS: HR 8.63 (95% CI 3.15-23.65)]. cHE is independently associated to the presence of SPSS (and total cross-sectional SPSS-area) and MELD. Furthermore, the presence of SPSS seems to increase the risk of cHE of developing of overt hepatic encephalopathy.

Impact of non-selective ß-blockers on hepatic encephalopathy in patients with liver cirrhosis

BackgroundNon-selective β-blockers (NSBB) are frequently used for the treatment of portal hypertension and gastroesophageal varices in patients with liver cirrhosis; however prospective studies investigating the potential association between NSBB use and hepatic encephalopathy (HE) are still scarce. We investigated the potential association between NSBB use and the presence of covert HE (CHE) as well as the development of overt HE (OHE). Methods224 patients with liver cirrhosis were included into this cohort study at two German centers and followed for a median of 364 days. CHE was diagnosed by pathological results in the PHES. Predictors for the presence of CHE or the development of OHE were analyzed using logistic-regression or cox-regression models. Results39% of patients were treated with NSBB and CHE was detected in 34% of patients at study inclusion. In logistic regression analysis, NSBB use, higher MELD score and a history of OHE were independently associated with the presence of CHE. Cumulative incidence of OHE was considerably higher in NSBB users than in non-users (p<0.001). In Cox-regression models NSBB use, presence of CHE, lower albumin and higher MELD score were independently associated with the development of OHE in the whole cohort as well as in the subgroup of patients with decompensated liver cirrhosis. NSBB use was independently associated with higher risk of mortality or need for liver transplantation in decompensated patients but not in the total cohort. ConclusionNSBB use seems to be associated with the presence of CHE as well as the development of OHE in patients with decompensated liver cirrhosis.

Incidence and Bedside Predictors of the First Episode of Overt Hepatic Encephalopathy in Patients With Cirrhosis.

Hepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for patients with cirrhosis. We aimed to determine the risk of and predictors for HE in contemporary patients. We prospectively enrolled 294 subjects with Child A-B (70% Child A) cirrhosis and portal hypertension without previous HE from July 2016 to August 2018. The primary outcome was the development of overt HE (grade >2). We assessed the predictive power of model for end-stage liver disease-sodium (MELD-Na) score, the Inhibitory Control Test, the Sickness Impact Profile score, and the Bilirubin-Albumin-Beta-Blocker-Statin score. We also derived a novel predictive model incorporating MELD-Na score, impact of cirrhosis on daily activity (Likert 1-9), frailty (chair-stands per 30 seconds), and health-related quality of life (Short-Form 8, 0-100). The cohort's median age was 60 years, 56% were men, and the median MELD-Na score was 9. During a follow-up of 548 ± 281 days, 62 (21%) had incident overt HE with 1-year probability of 14% ± 2%, 10% ± 2%, and 25% ± 5% for Child A and B. The best model for predicting the risk of overt HE included MELD-Na, Short-Form 8, impact on activity rating, and chair-stands within 30 seconds. This model-MELDNa-Actvity-Chairstands-Quality of Life Hepatic Encephalopathy Score-offered an area under the receiver operating curve (AUROC) for HE development at 12 months of 0.82 compared with 0.55, 0.61, 0.70, and 0.72 for the Inhibitory Control Test, Sickness Impact Profile, Bilirubin-Albumin-Beta-Blocker-Statin, and MELD-Na, respectively. The AUROC for HE-related hospitalization was 0.92. This study provides the incidence of HE in a well-characterized cohort of contemporary patients. Bedside measures such as activity, quality of life, and physical function accurately stratified the patient's risk for overt HE.

Association between diabetes mellitus and hepatic encephalopathy in patients with cirrhosis.

Diabetes mellitus may lead to increased serum ammonia and systemic inflammation thereby promoting hepatic encephalopathy (HE). To investigate the potential association between diabetes mellitus/glycaemic control and the presence of covert HE as well as the development of overt HE in a prospective setting. A total of 240 patients with liver cirrhosis were included into this prospective cohort study and followed for a median of 17 months. Covert HE was diagnosed by pathological results in the Portosystemic Hepatic Encephalopathy Score. Predictors for the presence of covert HE or the development of overt HE were analysed using logistic regression or Cox-regression models. At study inclusion, 65 patients (27.1%) presented with diabetes mellitus and covert HE was detected in 33.3%. Patients with diabetes mellitus had a more preserved liver function as compared to patients without diabetes mellitus (MELD 9 vs 10; P=0.043). In regression analyses after adjustment for confounders, diabetes mellitus was independently associated with the presence of covert HE at study inclusion and the development of overt HE during follow-up. These associations were confirmed in separate propensity-score-weighted regression models. In subgroup analyses, patients with worse glycaemic control (HbA1c >= 6.5%) had a pronounced risk for covert HE (OR 2.264, 95% CI 1.002-5.118) and overt HE (HR 4.116, 95% CI 1.791-9.459). Diabetes mellitus may associate with higher risk for the presence of covert HE and the development of overt HE in patients with liver cirrhosis. Adequate glycaemic control may be a potential target to attenuate this important complication.

Raised serum Interleukin-6 identifies patients with liver cirrhosis at high risk for overt hepatic encephalopathy.

Systemic inflammation is a driving force for the development of hepatic encephalopathy and recent studies demonstrated that elevated Interleukin-6 (IL-6) serum levels are associated with the presence of minimal hepatic encephalopathy in patients with liver cirrhosis. To test the hypothesis that IL-6 is a suitable marker to identify patients with liver cirrhosis at high risk for the development of overt hepatic encephalopathy. 201 patients were included into this prospective cohort study and were followed for a mean time of 322days. Covert hepatic encephalopathy was diagnosed according to the West-Haven criteria (hepatic encephalopathy grade 1) and with the portosystemic encephalopathy (PSE) test. The cumulative incidence of overt hepatic encephalopathy was higher in patients with IL-6 levels above the median of 9pg/mL than in patients with IL-6 levels at or below the median (35.6% vs 1.9%, P<.001). After adjustment for covert hepatic encephalopathy, history of overt hepatic encephalopathy, C-reactive protein (CRP) and model for end-stage liver disease (MELD), IL-6 levels above the median remained independently associated with the development of overt hepatic encephalopathy. The predictive performance of IL-6 regarding the development of overt hepatic encephalopathy during the next 180days (AUROC, 0.931) was numerically higher than that of MELD (AUROC, 0.841) or CRP (AUROC, 0.835). In patients without prior overt hepatic encephalopathy, the predictive performance of IL-6 (AUROC, 0.966) was even significantly higher than that of MELD (AUROC 0.843) or CRP (AUROC 0.850). The ideal cut-off for IL-6 in this setting was 23.5pg/mL with a sensitivity and specificity of 89.3% and 89.5% respectively. IL-6 serum levels are closely linked to the development of overt hepatic encephalopathy in patients with liver cirrhosis.

P: 17 The Two-year Outcome in Patients With MHE and Sarcopenia on Mortality and the Development of OHE

BACKGROUND: Hepatic encephalopathy is a significant complication of liver cirrhosis that is associated with a worse prognosis but also a poorer quality of life. The combination of sarcopenia and hepatic encephalopathy has a cascading and deleterious effect on both conditions. The aim of this study was to evaluate the long-term outcomes in patients who have minimal hepatic encephalopathy (MHE) and sarcopenia on mortality and the development of overt hepatic encephalopathy (OHE). METHODS: In this prospective trial, patients with liver cirrhosis at The Prince Charles Hospital were enrolled and followed for an average two years. An extensive exclusion criterion was used to reduce confounding factors; this included: active psychiatric condition, IVDU/drug use, neurological conditions, current significant alcohol intake, stroke, dementia, ongoing infection, language barrier, active malignancy, vision impairment, uncontrolled sleep apnoea, electrolyte disturbance and grade 1–4 encephalopathy. The diagnosis of MHE was Encephalapp Stroop test (Stroop) &gt;190, Psychometric hepatic encephalopathy score (PHES) &lt; −4 and Critical Flicker Frequency (CFF) &lt;39. The diagnosis of sarcopenia was completed using hand grip strength comparing to standard deviation data based on sex and age. A subset of participants underwent a DEXA scan to assess for lean body mass. Participant's clinical and electronic notes were assessed to evaluate mortality and the development of OHE. RESULTS: A total of 187 patients with a diagnosis of cirrhosis were approached for recruitment in the trial. 98 patients were excluded, whilst 17 patients declined. A total of 72 participants were enrolled in the trial. 37 participants had MHE whilst 35 participants did not have MHE. 16 participants had sarcopenia and MHE, whilst 14 participants had sarcopenia with no MHE. Over the average two year follow up, participants who did not have MHE and were not sarcopenic did not develop overt hepatic encephalopathy. Whilst participants with MHE and Sarcopenia had a significantly higher risk of developing OHE and mortality as can be seen in Figure 1 P value &lt;0.05. The Stroop test had the highest sensitivity 70% [CI 47%–86%] whilst the CFF had the highest specificity 78 % [CI 66%–87%] P value 0.005. In the subset analysis of patients who underwent a DEXA scan to assess lean body mass, this was not able to predict the risk of developing OHE. CONCLUSIONS: MHE and Sarcopenia assessment can be easily completed as a bedside clinical test to predict the long-term risk of mortality and the development of overt hepatic encephalopathy.

P: 28 Decreased Mean Kurtosis in the Putamen Is a Diagnostic Feature of Minimal Hepatic Encephalopathy in Patients With Cirrhosis

BACKGROUND: To prevent development of overt hepatic encephalopathy, early intervention for minimal hepatic encephalopathy (MHE) based on accurate diagnosis is essential. This study evaluated to investigate whether magnetic resonance diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) could detect brain microstructure abnormalities in MHE. The aim was to confirm whether brain microstructure abnormalities detected by magnetic resonance imaging were used as diagnosis of MHE. METHODS: Thirty-two subjects were prospectively examined with a 3-T MR scanner. Tract-based spatial statistics and region of interest analyses of diffusion imaging were performed to compare mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values between patients with/without minimal hepatic encephalopathy. Diagnostic performance for detection of MHE was assessed with the receiver operating characteristic analysis. RESULTS: Ten subjects were diagnosed as MHE by neuropsychological testing. After exclusion of unsuitable subjects, we analyzed 9 subjects with MHE and 14 subjects without MHE. There were no significant differences in the sex, age, and etiology of liver cirrhosis (alcohol/HCV/NAFLD; 4/3/2 vs 7/3/4, P = 0.87) in the MHE group and non-MHE group. In TBSS, compared with FA and MD, MK detected the broadest area with significant changes in the white matter of patients with MHE (MK, 54.8%; FA, 34.3%; MD, 4.0%, respectively). Regarding ROI analysis in the basal ganglia, FA values of the caudate nucleus (CN), putamen (Put), and globus pallidus (GP) were significantly lower in the MHE group (0.15, 0.19, and 0.29, respectively) when compared with the non-MHE group (0.16, 0.21, and 0.32, respectively) (P = 0.012, 0.002, and 0.0001, respectively). In contrast, MD values in the basal ganglia showed no apparent differences between the groups. Subsequently, we performed ROC analysis on the sites where significant differences were found in the ROI analysis. Among the metrics, MK values of the Put achieved AUROC of 0.90, and sensitivity, specificity, positive predictive value, and negative predictive value of more than 80% (0.89, 0.86, 0.80, and 0.92, respectively) between the MHE and non-MHE groups. In conclusion, mean kurtosis on the putamen was a useful finding to distinguish patients with MHE among subjects with liver cirrhosis. CONCLUSIONS: DKI detects changes in the cerebral white matter and basal ganglia regions of the patients with MHE more sensitively than DTI. MK values in the putamen can be a useful marker for diagnosing MHE from cirrhotic patients without MHE.