HE is a major cause of poor quality of life in patients with cirrhosis. A simple diagnostic test to identify minimal hepatic encephalopathy (MHE) and predict future overt HE (OHE) is lacking. We aimed to evaluate if analysis of speech patterns using a modern speech platform (1) correlates with validated HE tests, (2) correlates with MHE, and (3) predicts future OHE.

In a two-center prospective cohort study of 200 outpatients with cirrhosis and 50 controls, patients underwent baseline speech recording and validated HE diagnostic testing with psychometric HE score. Patients were followed for 6 months to identify episodes of OHE. Seven hundred fifty-two speech variables were extracted using an automated speech analysis platform, reflecting the acoustic, lexical, and semantic aspects of speech. Patients with cirrhosis were median 63 years old (IQR 54, 68), 49.5% (99) were female. Over 100 speech variables were significantly associated with psychometric HE score ( p <0.05 with false discovery rate adjustment). A three-variable speech model (2 acoustic, 1 speech tempo variable) was similar to animal naming test in predicting MHE (AUC 0.76 vs. 0.69; p =0.11). Adding age and MELD-Na improved the accuracy of the speech model (AUC: 0.82). A combined clinical-speech model ("HEAR-MHE model") predicted time to OHE with a concordance of 0.74 ( p =0.06).

Automated speech analysis is highly correlated with validated HE tests, associated with MHE, and may predict future OHE. Future research is needed to validate this tool and to understand how it can be implemented in clinical practice.

Sarcopenia, characterized by loss of muscle mass and function, has gained importance in the evaluation of cirrhotic patients. Evidence suggests its role in adverse clinical outcomes, including minimal hepatic encephalopathy (MHE). This study aimed to investigate the association between sarcopenia and MHE in patients with cirrhosis.

We prospectively enrolled outpatients with cirrhosis to assess sarcopenia using the 2019 criteria from the Asian Working Group for Sarcopenia. MHE was diagnosed through the Psychometric Hepatic Encephalopathy Score.

Of the 210 cirrhotic patients (57.1% male, mean age 62.7 ± 9.6 years), 54 (25.7%) had sarcopenia, with 26 (12.3%) classified as severe. Thirty-seven patients (17.6%) were diagnosed with MHE. Sarcopenia prevalence was significantly higher in patients with MHE compared to those without MHE (45.9% vs. 21.4%). MHE was significantly associated with age, education level, Mini-Mental State Examination score, and a history of hepatic decompensation. No significant associations were found regarding gender, body mass index, comorbidities, sleep quality, and the etiology of cirrhosis. Multivariable logistic regression showed that MHE was significantly associated with age (adjusted odds ratio [aOR] 1.08, 95% CI 1.02-1.13), sarcopenia (aOR 3.29, 95% CI 1.44-7.50), history of overt hepatic encephalopathy (aOR 7.40, 95% CI 1.20-45.56), and variceal bleeding (aOR 3.13, 95% CI 1.38-7.10). Severe sarcopenia was also independently associated with MHE (aOR 3.64, 95% CI 1.32-10.05).

Sarcopenia is prevalent in cirrhotic patients and is associated with an increased risk of MHE. Our findings emphasize the importance of assessing sarcopenia to potentially mitigate MHE risk in managing patients with cirrhosis.

Patients with cirrhosis are at risk of developing hepatic encephalopathy (HE), which can present with a wide range of symptoms, including confusion, lethargy, inappropriate behavior, and altered sleep patterns. In addition to HE, patients with cirrhosis are at risk of developing mild cognitive impairment, dementia, and delirium, which have features closely resembling HE. Given the similar presentation of these conditions, misdiagnosis can and does occur. Mild cognitive impairment is common in individuals aged 50 years and older and can progress to dementia in those affected. Dementia and HE are both characterized by sleep disturbance and cognitive dysfunction, thus differentiating these conditions can be difficult. Furthermore, delirium can disrupt sleep patterns, and liver disease is recognized as a risk factor for its development. As HE is a cirrhosis-related complication, determining if a patient has undiagnosed cirrhosis is critical, particularly given the large number of patients with asymptomatic, compensated cirrhosis. Separately, underdiagnosis of minimal HE can occur even in patients with diagnosed liver disease, related, in part, to lack of testing. Given the availability of effective therapies for managing symptoms and preventing future episodes, accurate diagnosis of HE is essential.

Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with liver cirrhosis, leading to neurotoxic effects and hepatic encephalopathy (HE). HE manifestations can range from mild, subclinical disturbances in cognition, or minimal HE (mHE) to gross disorientation and coma, a condition referred to as overt HE. Many blood-based biomarkers reflecting these neurotoxic effects of ammonia and liver disease can be measured in the blood allowing the development of new biomarkers to diagnose cirrhosis patients at risk of developing HE. The effect of ammonia on the brain is modulated by severity of systemic inflammation, and both hyperammonemia and inflammation can induce oxidative stress, which may mediate the neurological alterations associated to HE. This review aims to provide the latest evidence on biomarkers of HE beyond ammonia. We present different approaches to predict overt HE based on the combination of blood ammonia with some analytical and clinical parameters. Magnetic resonance analysis of brain images could also provide sensitive diagnostic biomarkers based on neuroimaging parameters. Some reports suggest that markers of systemic inflammation, oxidative stress, and central nervous system-derived components, may serve as additional biomarkers of HE. The involvement of extracellular vesicles and microbiota in the pathophysiology of mHE and HE has recently acquired importance and it would be interesting to explore their usefulness as early biomarkers of the disease. It is important to have a biomarker or a combination of them for early diagnosis of mHE to improve its treatment and prevent progression to overt HE.

As a potential sequela of cirrhosis, hepatic encephalopathy (HE) significantly impacts the lives of patients and caregivers and places a substantial burden on the healthcare system. With an increasing incidence over time and a cumulative effect on cognition, HE adversely effects quality of life, morbidity and mortality in patients with cirrhosis. HE can range from minimal or covert (MHE/CHE) to overt and symptomatic (OHE). HE has profound impacts on the health and wellbeing of patients and their families and caregivers. Effective treatments could improve the quality of life for all those affected. In this article, we discuss the existing treatments for HE and focus on the potential role of albumin in the treatment of HE. Currently approved therapies for HE (lactulose and rifaximin) are focused on decreasing the formation of ammonia in the gastrointestinal tract. Among the many agents with alternative mechanisms being investigated for treatment of HE, albumin has been studied in clinical trials with acute (≤ 3 days), short-term (up to 2 weeks) prolonged (> 2 weeks) and long-term administration (months). Current studies indicate that acute or short-term administration of albumin does not provide significant benefit for patients with OHE. However, there is increasing evidence that prolonged or long-term albumin therapy can help improve cognition in OHE and prevent recurrence. Additional studies are needed to substantiate these positive findings for longer term administration of albumin in HE and to increase our comprehension of the pharmacologic basis of the effects of albumin.

Hepatic encephalopathy (HE) is a critical neuropsychiatric complication of liver cirrhosis with a significant impact on patient quality of life and survival. The global prevalence of cirrhosis and associated HE necessitates a comprehensive understanding of the condition and effective systems of care to optimize outcomes. This review addresses the epidemiology, classification, diagnosis, and management of HE, with an emphasis on systems of care that improve outcomes for people with HE. Current diagnostic challenges include differentiating cognitive deficits attributable to HE from those caused by other etiologies, highlighting the need for accurate diagnostic methods. Traditional psychometric tests, while valuable for diagnosing covert HE (CHE), are limited in their ability to predict overt HE (OHE) due to various confounding factors. As a result, non-psychometric tools have been developed to provide outcome-based predictions aligned with the clinical course of HE. The management of HE includes addressing precipitating factors, pharmacologic interventions to reduce ammonia levels, and supportive care, with lactulose and rifaximin playing a central role. Preventive strategies with the use of remote monitoring in the outpatient management of HE, integrating technology for real-time tracking of therapy compliance and symptom evolution, could contribute to reducing hospital readmissions and improving patient care.

Hepatic encephalopathy (HE) is a marker of poor prognosis in adults with chronic liver disease (CLD). We prospectively studied the prevalence and precipitants of HE in children with CLD as there is a paucity of literature on the same.

Children (1-18 years) admitted with CLD were examined daily for the presence and grading of HE (West Haven/Whittington grading). Precipitants were classified as infection, dyselectrolytemia, gastrointestinal bleeding, constipation and dehydration. Changes in grades of HE and outcome were noted.

One hundred and sixty children (age 120 [84-168] months) were enrolled. HE was present in 50 (31.2%) patients with a total of 61 episodes. Maximum grade of HE was grade I (n = 16), II (n = 23), III (n = 11) and IV (n = 11). Forty-two cases had single and 8 had recurrent (2-5) episodes. Median duration of HE episodes was 96 (72-192) hours. Precipitants were identified in 55/61 (90.2%) episodes with infection (45/61, 73.7%) and dyselectrolytemia (33/61, 54%) being the most common. Lower albumin and sodium, higher INR and presence of infection were significantly associated with presence of HE. Overall, HE resolved in 33 (54%) episodes, while it progressed and persisted in 28 (45.9%) episodes. Patients with HE had a poorer outcome (25/50 vs 13/110; P < 0.01) with both higher in-hospital (11/50 vs 9/110; P = 0.02) and 1-month post discharge (14/39 vs 4/101; P < 0.01) mortality than those without HE.

One-third of admitted CLD children have HE, with identifiable precipitants in 90% of cases. Children with HE have poorer liver functions, higher rate of infections and worse outcome than those without HE.

Although it is well admitted that cirrhotic patients display various causes of neurocognitive impairment (NI) hampering the diagnosis of covert hepatic encephalopathy (CHE), those are almost never investigated per se. The aims of this study were, in cirrhotic patients displaying cognitive complaints explored by a complete multimodal work-up, to assess: (1) the prevalence of CHE and/or that of other causes of NI and (2) their outcomes, according to the cause of NI.

Prospective cohort of cirrhotic patients referred in a dedicated clinic because of cognitive complaints. Work-up included a complete neuropsychological assessment, electroencephalogram (EEG) and brain magnetic resonance imaging with spectroscopy. The diagnosis of CHE was made by an adjudication committee involving the physicians/neuropsychologist.

One hundred and twenty-three patients were included (alcohol/MASLD/virus in 63/53/14%, MELD = 11). Sixty-six per cent of them were diagnosed with CHE; among them, 73% exhibited also other causes of NI, mainly cerebrovascular diseases/psychiatric. Among patients without CHE, 48% and 59% displayed pathological Psychometric Hepatic Encephalopathy Score and animal naming test, respectively. Clinical improvement was observed in 77% of the patients re-evaluated after specific management. CHE, but not the other causes of NI, was independently associated with OHE occurrence.

Other causes of NI than CHE are frequent in patients with cirrhosis, and not ruled-out by the classical tests dedicated to CHE. Prognosis was influenced by the cause of NI. The management of patients even without CHE led to clinical improvement, underlining the need for a multifaceted approach of cirrhotic patients with cognitive complaints.

The transition from compensated to decompensated cirrhosis is crucial, drastically reducing prognosis from a median survival of over 10 years to 2 years. There is currently an unmet need to accurately predict decompensation. We systematically reviewed and meta-analysed data regarding biomarker use to predict decompensation in individuals with compensated cirrhosis.

PubMed and EMBASE database searches were conducted for all studies from inception until February 2024. The study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality of Prognosis Studies framework was used to assess the risk of bias. The meta-analysis was conducted with a random effects model using STATA software.

Of the 652 studies initially identified, 63 studies (n=31 438 patients) were included in the final review, examining 49 biomarkers. 25 studies (40%) were prospective with the majority of studies looking at all-cause decompensation (90%). The most well-studied biomarkers were platelets (n=17), Model for End-Stage Liver Disease (n=17) and albumin (n=16). A meta-analysis revealed elevated international normalised ratio was the strongest predictor of decompensation, followed by decreased albumin. However, high statistical heterogeneity was noted (l2 result of 96.3%). Furthermore, 21 studies were assessed as having a low risk of bias (34%), 26 (41%) moderate risk and 16 (25%) high risk.

This review highlights key biomarkers that should potentially be incorporated into future scoring systems to predict decompensation. However, future biomarker studies should be conducted with rigorous and standardised methodology to ensure robust and comparable data.

Polypharmacy and anticholinergic medications are associated with cognitive decline in elderly populations. Although several medications have been associated with HE, associations between medication burden, anticholinergics, and HE have not been explored. We examined medication burden and anticholinergics in patients with cirrhosis and their associations with HE-related hospitalization.

We conducted a retrospective cohort study of patients aged 18-80 with cirrhosis seen in hepatology clinics during 2019. The number of chronic medications (medication burden) and anticholinergic use were recorded. The primary outcome was HE-related hospitalization.

A total of 1039 patients were followed for a median of 840 days. Thirty-seven percent had a history of HE, and 9.8% had an HE-related hospitalization during follow-up. The mean number of chronic medications was 6.1 ± 4.3. Increasing medication burden was associated with HE-related hospitalizations in univariable (HR: 1.09, 95% CI: 1.05-1.12) and multivariable (HR: 1.07, 95% CI: 1.03-1.11) models. This relationship was maintained in those with baseline HE but not in those without baseline HE. Twenty-one percent were taking an anticholinergic medication. Anticholinergic exposure was associated with increased HE-related hospitalizations in both univariable (HR: 1.68, 95% CI: 1.09-2.57) and multivariable (HR: 1.71, 95% CI: 1.11-2.63) models. This relationship was maintained in those with baseline HE but not in those without baseline HE.

Anticholinergic use and medication burden are both associated with HE-related hospitalizations, particularly in those with a history of HE. Special considerations to limit anticholinergics and minimize overall medication burden should be tested for potential benefit in this population.

Portal hypertension has cerebral consequences via its causes and complications, namely hepatic encephalopathy (HE), a common and devastating brain disturbance caused by liver insufficiency and portosystemic shunting. The pathogenesis involves hyperammonemia and systemic inflammation. Symptoms are disturbed personality and reduced attention. HE is minimal or grades I to IV (coma). Bouts of HE are episodic and often recurrent. Initial treatment is of events that precipitated the episode and exclusion of nonhepatic causes. Specific anti-HE treatment is lactulose. By recurrence, rifaximin is add-on. Anti-HE treatment is efficacious also for prophylaxis, but emergence of HE marks advanced liver disease and a dismal prognosis.

To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks.

In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of ModelC-V, we compared it with four previous models, both in discrimination and calibration.

The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, ModelC-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups.

Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies.

The aim was to examine rifaximin plus lactulose efficacy in patients with cirrhosis at a risk of developing overt HE who were stratified by important baseline characteristics such as comorbid ascites or diabetes.

Pooled post hoc subgroup analysis of adults receiving rifaximin 550 mg twice daily plus lactulose or lactulose alone for 6 months in a phase 3 randomized, double-blind trial and a phase 4 open-label trial was conducted.

Rifaximin plus lactulose was more efficacious than lactulose alone for reducing the risk of overt HE recurrence and HE-related hospitalization in adults grouped by select baseline disease characteristics.

Minimal hepatic encephalopathy (MHE) is a pervasive frequent complication of cirrhosis of any etiology. The diagnosis of MHE is difficult as the standard neurologic examination is essentially within normal limits. None of the symptoms and signs of overt HE is present in a patient with MHE, such as confusion, disorientation, or asterixis. Progress has been made in diagnostic tools for detection of attention and cognitive deficits at the point of care of MHE. The development of MHE significantly impacts quality of life and activities of daily life in affected patients including driving motor vehicles and machine operation.

Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid-lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, antiproliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and nonviral etiologies of CLD and hepatocellular carcinoma (HCC), and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

Hepatic encephalopathy (HE) is a severe complication of cirrhosis, independently associated with a poor survival. The objectives of this study were to describe the prevalence of overt hepatic encephalopathy (OHE) requiring hospitalization, and the healthcare pathways and outcomes of patients hospitalized for OHE in France. Data from the French Hospital-Discharge Database (Programme de Medicalisation des Systemes d'information, PMSI) within the 5-year period from 2014 to 2018 were analysed. Since the disease lacks a PMSI code in the ICD-10, an identification algorithm was developed. The analysis identified 57,191 patients with OHE including 48,566 patients (85 %) who had been hospitalized twice or more during the study period. Each year, an average of over 20,000 patients were hospitalized in France for OHE as the primary or secondary reason for hospitalization. Among these patients, between 11,500 and 13,500 had been hospitalized at least twice in that year with an average of 3.4 hospitalisations per year. 25 % of admissions occurred following consultation at the emergency unit. Among hospitalisations, 15 % involved admission to the critical care resuscitation unit or intensive care. For all patients identified as suffering from OHE and hospitalized, the 5-year mortality was 46.5 % (26,621 patients). This pioneering study revealed that, in France, despite a probable underestimation of OHE episodes due to the lack of specific PMSI coding, the prevalence of OHE was very high, with frequent recurrences and readmissions, and high mortality.

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.

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.

Poor patient-reported outcomes (PROs) are common in cirrhosis, including poor sleep and health-related quality of life (HRQOL). HE is a major driver of poor PROs. Many clinicians initiate lactulose therapy to address poor PROs. PRO-triggered therapy, however, has not been studied till date.

We conducted a 28-day randomized trial of crystalline lactulose therapy (20 g BID) compared with no HE-directed therapy in 52 patients with cirrhosis, portal hypertension, no prior HE, and high Work Productivity and Activity Impairment scores (0-10) attributed to cirrhosis. The primary outcome was change in global HRQOL measured with Short Form-8 Health Survey. Secondary outcomes included change in Animal Naming Test score, Work Productivity and Activity Impairment, and sleep quality (scored "very bad" to "very good").

Overall, 52 patients underwent randomization; 3 subjects withdrew from the crystalline lactulose arm (1 before medication initiation, 1 due to an unrelated condition, and 1 due to high baseline bowel movements). The average age was 60 years, the average Model for Endstage Liver Disease-Sodium score was 10.5, and 56% of the patients had ascites. Baseline bowel movements were 2.3/day, with 35% of the patients having Bristol Stool Scale >4. At 28 days, there was no improvement in HRQOL: patients receiving crystalline lactulose had an 8.1-point (95% CI: 3.7-12.4) increase compared with 6.6 (95% CI: 2.3-10.8) in the control group ( p = 0.6). Lactulose was associated with a significantly ( p = 0.002) increased Animal Naming Test score (3.7, 95% CI: 2.1-5.4) versus the control group (0.2, 95% CI: -1.7, 1.4). Lactulose users reported more good sleep (92% vs. 52%, p = 0.001) and lower activity impairment (3.0 vs. 4.8, p = 0.02).

Lactulose improves sleep and activity impairment in patients with poor PROs. We did not observe any improvement in global HRQOL after 28 days using the Short Form-8 Health Survey instrument.

The clinical course of patients with liver cirrhosis and adherence to hepatocellular carcinoma (HCC) screening guidelines are not well studied in the Netherlands. We investigated this and potential risk factors for decompensation and transplant-free survival (TFS) in a large regional cohort.

We performed a retrospective cohort study of patients with confirmed liver cirrhosis in Amsterdam, the Netherlands. Clinical parameters, decompensation events, development of HCC, and medication use were extracted from medical records.

In total, 681 hospitalized and outpatients were included. Mortality risk was increased by: age (aHR 1.07, p < 0.01), smoking (aHR 1.83, p < 0.01), decompensated initial presentation (aHR 1.43, p = 0.04) and increased MELD (aHR 1.07, p < 0.01). PPI use tended to increase mortality risk (aHR 1.35, p = 0.05). The risk of future decompensation was increased with increased age (aHR 1.02, p < 0.01), decompensated initial presentation (aHR 1.37, p = 0.03) and alcohol misuse as etiology (aHR 1.34, p = 0.04). Adequately screened patients for HCC had a longer TFS compared to patients who were not (48 vs 22 months), p < 0.01).

In patients with cirrhosis, decompensation at initial presentation was associated with an increased risk of future decompensation and mortality. Alcoholic cirrhosis was associated with an increased risk of future decompensation. Adequate HCC surveillance was associated with markedly better survival.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40-50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.

It remains challenging to identify covert hepatic encephalopathy and predict progression to overt hepatic encephalopathy. Psychometric testing is a widely used diagnostic modality, but it is often inaccurate and difficult to implement in diverse populations, making it a less than ideal assessment. Alternatively, by using easily accessible data from the electronic health record, simple clinical assessment tools, and patient-reported outcomes, we may be better able to predict hepatic encephalopathy across multiple populations. Furthermore, incorporation of patient-reported outcomes into our diagnostic toolset not only aids detection of covert hepatic encephalopathy and prediction of overt hepatic encephalopathy, but also allows us to target therapies and track their impact. Herein, we outline a potential algorithm based on these easily integrated tools to promote patient risk-stratification and early therapeutic intervention.

Hepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for cirrhosis patients. This study aimed to develop and validate machine learning (ML) models to predict 28-day mortality for patients with HE.

A retrospective cohort study was conducted in the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients from MIMIC-IV were randomized into training and validation cohorts in a ratio of 7:3. Training cohort was used for establishing the model while validation cohort was used for validation. The outcome was defined as 28-day mortality. Predictors were identified by recursive feature elimination (RFE) within 24 h of intensive care unit (ICU) admission. The area under the curve (AUC) and calibration curve were used to determine the predictive performance of different ML models.

In the MIMIC-IV database, 601 patients were eventually diagnosed with HE. Of these, 112 (18.64%) experienced death within 28 days. Acute physiology score III (APSIII), sepsis related organ failure assessment (SOFA), international normalized ratio (INR), total bilirubin (TBIL), albumin, blood urea nitrogen (BUN), acute kidney injury (AKI) and mechanical ventilation were identified as independent risk factors. Validation set indicated that the artificial neural network (NNET) model had the highest AUC of 0.837 (95% CI:0.774-0.901). Furthermore, in the calibration curve, the NNET model was also well-calibrated (P = 0.323), which means that it can better predict the 28-day mortality in HE patients. Additionally, the performance of the NNET is superior to existing scores, including Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease-Sodium (MELD-Na).

In this study, the NNET model demonstrated better discrimination in predicting 28-day mortality as compared to other models. This developed model could potentially improve the early detection of HE with high mortality, subsequently improving clinical outcomes in these patients with HE, but further external prospective validation is still required.

Proton pump inhibitors (PPIs) are commonly prescribed to prevent and treat upper gastrointestinal ulceration and bleeding. Studies have identified increased incidence of spontaneous bacterial peritonitis and hepatic encephalopathy (HE) in cirrhosis patients taking PPIs. However, results are conflicting, and as PPIs are prescribed for variceal bleeding, a major risk factor for infection and HE, it is challenging to discern whether these associations are causal.

In this post-hoc analysis of the ATTIRE trial, we pooled all patient data to investigate the effects of PPI use on clinical outcomes. ATTIRE was a multicentre, open-label, randomised trial of targeted 20% human albumin solution (HAS) daily infusions versus standard care involving 777 adults with decompensated cirrhosis hospitalised with acute complications and albumin <30 g/L. Study recruitment was between Jan 25, 2016, and June 28, 2019, at 35 hospitals across England, Scotland, and Wales. Key exclusion criteria were advanced hepatocellular carcinoma with life expectancy <8 weeks and patients receiving palliative care. In ATTIRE, patients were grouped by PPI use at trial entry. We studied infection and HE at baseline and incidence of hospital acquired infection, new onset HE, renal dysfunction and mortality. We attempted with propensity score matching to account for differences in disease severity.

Overall PPI use at baseline was not associated with increased incidence of infection, renal dysfunction or mortality, but was associated with significantly increased incidence of grade III/IV HE during hospital stay (P = 0.011). This was only significant for those taking intravenous PPIs and these patients had >10 times the incidence of variceal bleeding and near double the 28-day mortality compared to non-PPI patients. However, propensity score matching was not possible as there was such a strong selection of patients for PPI use, that we could not find sufficient non-PPI patients to match to. We found no impact of PPI use on plasma markers of bacterial translocation, infection or systemic inflammation.

Our real-world data from a completed randomised trial show that PPIs are widely prescribed in the UK and judicious use appears safe in patients hospitalised with decompensated cirrhosis. However, patients prescribed PPIs had fundamentally different phenotypes to those not prescribed PPIs, a form of confounding by indication, which should be strongly considered when interpreting studies and making recommendations about their use.

Wellcome Trust and Department of Health and Social Care.

Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.

To establish an early warning model of hepatic encephalopathy in patients with liver cirrhosis based on psychological testing.

Data including patient demographics, number connection test-A (NCT-A), digit symbol test (DST), Model for End-Stage Liver Disease (MELD) scores were collected for patients admitted to a tertiary hospital in Shanghai with liver cirrhosis between January and December 2019. Patients were divided into two groups based on the development of hepatic encephalopathy (the hepatic encephalopathy group and non-hepatic encephalopathy group). Risk factors for hepatic encephalopathy in patients with liver cirrhosis were determined by using the binary logistic regression. We developed a predictive model in accordance with the STARD statement criteria (Supplementary File S1) with a cut-off value determined by receiver operating characteristic (ROC) curve analysis and calculation of the Youden index.

A total of 417 patients with liver cirrhosis were included in the present study. Of these, 33 out of 66 patients with abnormal psychological tests had hepatic encephalopathy during hospitalisation. In contrast, 6 out of 317 patients with normal psychological tests had hepatic encephalopathy. Logistic regression analysis identified age, MELD score, and abnormal psychological tests as risk factors for hepatic encephalopathy in patients with liver cirrhosis. The area under the ROC curve for our prediction model for hepatic encephalopathy in patients with liver cirrhosis was 0.950 and the largest calculated Youden index was 0.804, which corresponds to a cut-off value is 0.0307.

Greater age, higher MELD score and abnormal psychological tests were significantly associated with increased risk of hepatic encephalopathy indicating early warning systems and identification of abnormal psychological tests are important components of the clinical nursing care process for cirrhotic patients. Our early warning model based on psychological testing can provide a basis for nursing observation and prevention of hepatic encephalopathy.

Risk assessments for hepatic encephalopathy according to liver function and psychological tests, in addition to traditional neurological observations and dietary guidance, have utility in decreasing the incidence of hepatic encephalopathy.

Covert hepatic encephalopathy (CHE) adversely affects clinical outcomes in patients with liver cirrhosis, although its diagnosis is difficult. This study aimed to establish a simple CHE screening model based on blood-related biochemical parameters.

This retrospective study enrolled 439 patients who were assessed for CHE using a neuropsychiatric test between January 2011 and June 2019. A simple CHE (sCHE) score was calculated with hypoalbuminemia (≤ 3.5 g/dL) and hyperammonemia (≥ 80 μg/dL) as 1 point each. The association between sCHE score and CHE or overt hepatic encephalopathy (OHE) was assessed using logistic regression and Fine-Gray competing risk regression models.

Of 381 eligible patients, 79 (21%) were diagnosed with CHE. The distribution of sCHE scores was 48% with 0 point, 33% with 1 point, and 19% with 2 points. Patients with sCHE score ≥ 1 point had a higher prevalence of CHE than those with sCHE score of 0 (27% vs. 14%, P = 0.002). A cut-off value of 1 point showed high discriminative ability for identifying CHE, with a sensitivity of 0.67, specificity of 0.56, positive predictive value of 0.27, and negative predictive value of 0.86. During the median follow-up period of 2.2 years, 58 (15%) patients developed OHE. Multivariate analysis showed that sCHE score ≥ 1 (sub-distribution hazard ratio [SHR], 2.69; 95% confidence interval [CI], 1.41-5.15) and CHE (SHR, 2.17; 95% CI, 1.26-3.73) independently predicted OHE.

The sCHE score is a useful screening model for identifying patients with CHE and for predicting OHE occurrence.

The incidence of, risk factors for, and outcomes after the development of ascites are poorly described for contemporary patients with cirrhosis.

We examined data for a 20% random sample of US Medicare enrollees with cirrhosis and Part D prescription coverage from 2008 to 2019, excluding patients with heart failure and diuretic use prior to cirrhosis. Among 63,364 persons with cirrhosis, we evaluated the incidence of ascites using an Aalen-Johansen estimator. We evaluated risk factors for ascites, mortality, and mortality after ascites using multistate modeling. We determined the associations with each outcome for an array of medication exposures including nonselective beta-blockers, antiviral therapy, statins, rifaximin, anticoagulants, and metformin.

The cumulative incidence of ascites was 5.1%, 9.5%, and 10.7% and 1, 3, and 5 years overall. The corresponding data for ascites requiring paracentesis were 1%, 2.1%, and 2.4%. Persons aged < 65 years, with alcohol-related cirrhosis, varices, or HE, are most likely to develop ascites. The risk of ascites was higher for persons taking any NSBB (including carvedilol) but lower for those taking atorvastatin (but not other statins) and antiviral therapy for Hepatitis C. Incident ascites was associated with increased risk of death, HR 27.6 95%CI(21.7-35.1). Survival following ascites was 1.08 years (interquartile range, IQR, 0.26-2.75), 0.38 years (IQR0.1-1.3) for those requiring paracentesis. Lipophilic statins were the only medications associated with lower mortality after ascites requiring paracentesis.

Ascites is associated with a high risk of death. Very few candidate therapies are associated with the reduction in the risk of ascites and mortality after ascites development.

Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We sought to determine whether race and ethnicity were associated with rifaximin prescriptions.

We examined data for a 20% random sample of United States Medicare enrollees with cirrhosis and hepatic encephalopathy treated with outpatient lactulose and Part D prescription coverage from 2011-2019. Beginning at the time of first diagnosis, we evaluated time to first prescription of rifaximin accounting for competing risks (Fine-Gray, yielding subdistribution hazard ratios [sHRs]) and cumulative rifaximin exposure using a gamma hurdle model (yielding exposure length ratios). We aimed to determine the association of race and ethnicity with each outcome, adjusting for demographics, clinical factors, and other features of clinical management.

Overall, 29,095 patients were diagnosed with HE and treated with lactulose, of whom 13,272 were prescribed rifaximin. Compared to White patients, Black patients were least likely to receive any prescription for rifaximin (sHR 0.70; 95% CI 0.65-0.76). Asian and Hispanic patients were also less likely to receive rifaximin compared to White patients. Black patients also received fewer doses of rifaximin (exposure length ratio 0.90; 95% CI 0.82-0.98). Hispanic patients also received fewer doses (0.88; 95% CI 0.80-0.98). Out-of-pocket spending on rifaximin per person-year was higher for Black and Hispanic than White patients. Out-of-pocket medication spending was associated with reduced odds of filling a rifaximin prescription. Black and Hispanic patients were least likely to be referred to a gastroenterologist.

In a national cohort of patients with HE, we observed stark racial and ethnic disparities in the use of rifaximin, an approved therapy for the improvement of HE-specific outcomes. Access to gastroenterologists and cost controls may reduce disparities.

Hepatic encephalopathy is a serious problem that can affect people with cirrhosis. When someone develops hepatic encephalopathy, there are 2 main treatments. The first-line treatment is called lactulose. If episodes of hepatic encephalopathy happen on lactulose, another treatment called rifaximin is recommended. In this study, we found that compared to White patients, Black and Hispanic patients are less likely to be prescribed rifaximin, receive fewer rifaximin refills, spend more on rifaximin, and have less access to subspecialists who are familiar with rifaximin. We conclude that efforts to address the cost of rifaximin and access to gastroenterologists could help improve these disparities.

Overt hepatic encephalopathy (OHE) is a serious complication of liver disease. We aimed to develop a dynamic nomogram for estimating the probability of 30-day transplant-free mortality in patients with OHE and hepatitis B-related cirrhosis (HBC).

We identified 402 patients with OHE and HBC at the Beijing Ditan Hospital between January 2011 and July 2016. Independent risk factors were determined using multivariate Cox proportional hazards regression analysis. A dynamic nomogram was established to predict the probability of 30-day transplant-free mortality. The discrimination and clinical usefulness of the nomogram were estimated using the area under the receiver operating characteristic (AUC) and calibration curves, and decision curve analysis. A prospective cohort of 208 patients was enrolled for validation.

The model for end-stage liver disease (MELD) score and neutrophil-to-lymphocyte ratio (NLR) were independently associated with the 30-day transplant-free mortality. The AUC values of the nomogram were 0.881 and 0.879 in the derivation and validation cohorts, respectively, and the discrimination ability was superior to that of the established models. The calibration plot fitted the predicted survival and observed probabilities well. The incidence of mortality was 2.0% (3/151) in patients with MELD scores < 23 and NLR < 4, and 55.4% (41/92) in those with MELD scores ≥ 23 and NLR ≥ 4.

The dynamic nomogram can predict the risk of 30-day transplant-free mortality in patients with OHE and HBC. Patients with MELD scores ≥ 23 and NLR ≥ 4 have a high mortality rate and should be admitted to intensive care.

Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes.

We conducted a narrative review of the literature focusing on the most recent advances.

We review the aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, and the current landscape of clinical trials for non-alcoholic steatohepatitis. We review the current standard of care and latest developments in the management of hepatic encephalopathy (HE), ascites and hepatorenal syndrome. We evaluate the promise and drawbacks of chemopreventative therapies that have been examined in trials and observational studies which may reduce the risk of hepatocellular carcinoma and cirrhosis complications. Finally, we examine the therapies which address the non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue.

The improvement of clinical and patient-reported outcomes for patients with cirrhosis is possible by applying evidence-based pharmacotherapeutic approaches to the prevention and treatment of cirrhosis complications.

In patients with cirrhosis and chronic liver disease, acute-on-chronic liver failure is emerging as a major cause of mortality. These guidelines indicate the preferred approach to the management of patients with acute-on-chronic liver failure and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.

Overt hepatic encephalopathy is a generally reversible neurologic complication of cirrhosis. Overt hepatic encephalopathy has been associated with poor hospitalization- and mortality-related outcomes, which is important given increasing hepatic encephalopathy-related hospitalizations over time. The aim of this narrative review is to provide an overview of hospital- and mortality-related outcomes in patients with overt hepatic encephalopathy and the pharmacologic therapies that may improve these outcomes. Guideline-recommended prophylaxis with lactulose (first-line therapy) or secondary prophylaxis with rifaximin plus lactulose decreases hospital admissions and mortality rates. Rifaximin or lactulose treatment was beneficial for reducing the hospitalization rate in patients with hepatic encephalopathy compared with no treatment. Further, retrospective studies have shown that rifaximin with or without lactulose was effective for decreasing the number of hepatic encephalopathy episodes, hepatic encephalopathy-related hospitalizations, and duration of hospitalization. Ornithine phenylacetate, an ammonia-reducing agent currently in development, is also being investigated in hospitalized patients with hepatic encephalopathy. Overall, data support that prophylaxis for the prevention of hepatic encephalopathy recurrence improves outcomes in patients with cirrhosis and a history of hepatic encephalopathy.

Hepatic encephalopathy (HE) is characterized by recurrence and poor quality of life. Acute-on-chronic liver failure (ACLF) mainly occurs in patients with chronic liver diseases and often presents with HE. Several predictive models have been proposed to predict the outcomes of these patients. Our study is aimed at identifying associated risk factors and the prognostic accuracies of predictive models in HE patients with or without ACLF.

Patients with liver cirrhosis were retrospectively enrolled. Risk factors were evaluated by multivariate regression analyses. The predictive capabilities of models were calculated using the receiver operating characteristic (ROC) curve analyses and compared by the DeLong tests. Outcomes were defined as in-hospital mortality, HE severity, and ACLF occurrence.

In multivariate regression analyses, serum biomarkers neutrophil and total bilirubin (TBIL) were independently correlated with in-hospital death. Alanine aminotransferase (ALT) and blood urea nitrogen (BUN) were independent serum biomarkers associated with HE severity. Hemoglobin, TBIL, BUN, and international normalized ratio (INR) were significant indicators associated with ACLF incidence. For prediction of in-hospital mortality, Child-Pugh was superior to the others in the whole patients, while NLR showed the best capability in the ACLF group.

In cirrhotic patients present with HE, BUN is a risk factor associated with HE severity and ACLF incidence. Child-Pugh and NLR scores may be effective prognosticators in patients with HE.

The purpose of the present document is to provide detailed information on the correct and optimal use of digital media to ensure continuity of care for gastroenterological patients in everyday clinical practice, in health emergencies and/or when the patient cannot reach the hospital for other reasons. During the recent COVID-19 pandemic, telemedicine has allowed many patients with chronic diseases to access remote care worldwide, proving to be the ideal solution to overcome restrictions and carry out non-urgent routine follow-ups on chronic patients. The COVID-19 pandemic has therefore made organizational and cultural renewal essential for the reorganization of healthcare in order to ensure greater continuity of care with a minimum risk of spreading the virus to users, practitioners and their families. These AIGO recommendations are intended to provide Italian gastroenterologists with a tool to use this method appropriately, in compliance with current legislation, in particular the proper approach and procedures for conducting a remote examination using a video conferencing tool, the so-called televisit. In the near future, telemedicine may contribute to a possible reorganization of healthcare systems, through innovative care models focusing on the citizen and facilitating access to services throughout the entire Country.

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 (<60 μg/dl). Zinc deficiency was observed more frequently in the patients with reduced liver function reserve. During the median follow-up period of 9.9 months, 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.

Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007-11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068-1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151-0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.

We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score.

Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS.

Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group.

The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.

Rifaximin is recommended as treatment for hepatic encephalopathy (HE) that targets intestinal bacterial flora. Although combined use with synthetic disaccharides is the standard of care worldwide, the therapeutic effects of rifaximin for overt encephalopathy (OHE) in Japanese patients have not been examined sufficiently. We examined the therapeutic effects of rifaximin for OHE in Japanese patients.

A total of 76 patients who developed OHE of West Haven grade II or higher at least once within the 12 months before starting rifaximin were included. Blood ammonia levels and the incidence of OHE during the 12 months before and after starting rifaximin therapy were compared in a before-and-after study. Rifaximin efficacy and predictors of efficacy were also examined.

Post-treatment blood ammonia levels were significantly lower than pretreatment levels. The mean annual number of OHE incidents and intravenous branched-chain amino acid preparations used per patient were significantly lower after starting rifaximin therapy (2.51 vs. 0.76 times/year, p < 0.001; and 71.9 vs. 20.7 preparations/year, p = 0.003, respectively). The cumulative incidence of hospitalizations associated with HE significantly decreased after rifaximin therapy (hazard ratio 0.187; p < 0.001). The efficacy rate, defined as the proportion of patients without OHE during the administration of rifaximin for 1 year after starting rifaximin therapy, was 65.8%. Serum albumin ≥2.7 g/dl was an independent predictor of efficacy.

Rifaximin was associated with decreased blood ammonia levels, lower incidence of OHE, and fewer hospitalizations in Japanese patients with HE. In addition, serum albumin level was an important predictor on efficacy of rifaximin.

Hepatic encephalopathy (HE) is a common complication of cirrhosis resulting in relapsing-remitting mental status changes ranging from deficits in executive function to coma. Incident HE is associated with an abrupt increase in mortality¹ and frequent hospitalization.² To further the understanding of the burden and impact of HE at the population level, valid algorithms are required to identify patients in administrative data. An International Classification of Diseases (ICD)-9 code is specific for HE (572.2), offering a 0.92 positive predictive value (PPV) and 0.36 negative predictive value (NPV).³ When applied in an algorithm to patients with ICD-9 codes for cirrhosis (eg, 571.5), Kanwal et al⁴ found a PPV and NPV of 0.86 and 0.87. Unfortunately, the switch to ICD-10 in 2015 rendered algorithms validated using ICD-9 invalid. Kaplan et al⁵ previously showed that lactulose and rifaximin use correlated with grade of HE for Child classification. Herein, we validate a diagnostic coding algorithm for HE using ICD-10 and medication records.

Hepatic encephalopathy (HE) is a common complication of cirrhosis that results in unpredictable neuropsychiatric symptoms and increases the risk of death and disability. In the current issue of Clinical and Translational Gastroenterology, Fabrellas et al. report on a qualitative study that assesses the psychological impact of HE on both patients and their informal caregivers. Both patients and caregivers report diminished quality of life driven by disruptive anxiety and feelings of fear and sorrow. There is a need to optimize therapy for encephalopathy and to address the shared psychological impact of HE experienced by both patients and caregivers.

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.