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.

Hepatic encephalopathy (HE), an outcome of chronic liver disease is characterized by behavioral impairments. The present study investigated the role of HDAC-mediated transcriptional regulation causing behavioral impairments in the bile duct ligation (BDL) model of HE. Post-BDL surgery in rats, dynamic alterations in liver function tests, liver morphology were observed. In BDL rats, histological staining in brain demonstrated reduced neuronal viability and warped neuronal architecture. Additionally, BDL animals showed impaired spatial learning, memory, and increased anxiety in the open field, Barnes maze, and Y maze tests. Further, the Golgi cox staining revealed a significantly altered spine density and spine clustering patterns of granular neuron in dentate gyrus of BDL rats. Concordantly, a significant downregulation of memory encoding genes was also observed in BDL rats that may account for aberrant behavior. Molecular analysis of modifiers, such as HDAC, showed significant changes in the expression of HDAC3 and HDAC6 in both the cortex and hippocampus of BDL rats. Upregulation of HDAC3 promoted its localization on the promoter of genes like c-Fos, NPAS4, Arc, and others, likely causing their decreased expression. Our findings suggest that increased HDAC3 activity downregulates key synaptic plasticity and memory-related genes, potentially driving neurobehavioral changes in BDL rats.

Medical screening is employed to detect early signs of diseases in asymptomatic populations, potentially improving patient outcomes through early intervention. However, the psychosocial impact of screenings remains a field of discussion. Inconsistent findings from studies, mainly originally from cancer research, are not easily transferable to the context of liver screening. This study aimed to identify predictors of psychosocial consequences in asymptomatic adults screened for early-stage liver cirrhosis, thereby contributing to the current knowledge on screening impact.

We analyzed data from 487 participants who underwent a systematic liver disease screening in Germany from January 2018 to February 2021. The screening involved blood tests, advanced diagnostics, and potentially, liver biopsies. We used bootstrapped LASSO regression with 10-fold validation to evaluate the influence of various predictors on psychosocial outcomes measured by the Psychological Consequences of Screening Questionnaire (PCQ).

The results show that severity of comorbidities (beta =  0.44-2.72), subjective social status (beta =  -0.30--0.86), and social support (beta =  -0.33--0.98) were consistent predictors across all psychosocial outcome measures by not covering zero in the confidence intervals. Older age (beta =  -0.03--0.08), the existence of a steady partnership (beta =  -1.08--0.48) and higher health literacy regarding the application of medical information (beta =  0.33-0.48) were associated with less psychosocial dysfunction, indicating their protective roles to prevent psychosocial burden of screening.

The study underscores the importance of considering individual patient characteristics in predicting psychosocial consequences of medical screening. Medical practitioners should consider personalized communication strategies taking into account the individual context of patients. The protective role of social support and stable personal relationships suggests that integrating psychosocial support services within screening programs could mitigate negative outcomes. Furthermore, increasing patient health literacy might help to demystify the screening process and can reduce psychosocial burden even if patients come from a segment of lower subjective social status.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portal-systemic shunting with a significant impact on patients' quality of life and healthcare systems. This narrative review was elaborated by the Special Interest Group (SIG) "Gender in Hepatology" of the Italian Association for the Study of the Liver (AISF) and addresses the underexplored area of sex differences in HE, examining epidemiological trends, clinical manifestations and potential underlying mechanisms. Current evidence suggests that men and women may experience different prevalence rates, risk factors and disease progression due to biological and psychosocial factors. However, these differences remain poorly understood, with limited research on sex-specific outcomes, treatment adherence and psychological effects. Emerging data on body composition, gut microbiota and experimental models highlight potential mechanisms contributing to these differences. Given the evolving epidemiology of liver disease, this review highlights the need for targeted studies and sex-specific approaches in the management of HE to advance personalised medicine and improve outcomes.

Hepatic encephalopathy (HE) presents a significant challenge in liver transplantation (LT). On the one hand, LT can provide a curative treatment for HE by addressing its underlying cause, suggesting HE should be a strong indication for LT. Conversely, the severity of HE may reflect advanced liver disease and significant neurocognitive impairment, potentially complicating post-transplant outcomes and raising concerns about its suitability as an indication. This review will provide helpful insight to the hepatologist deciding whether HE should be considered an indication or a contraindication to liver transplantation in their patient. It gives an overview of the burden of HE pretransplant, HE's current status in the transplant listing process, and pre- and post-transplant cognitive issues to be mindful of. The main take-away messages are that pre-transplant HE should be managed aggressively, that neurodegenerative disorders and other differential diagnoses to HE should be thoroughly excluded, and that immunosuppressants can cause new onset cognitive issues post-transplant and should be monitored closely. In the future, objective measures of HE severity should be included in the MELD score to enhance the fairness and efficacy of transplant listings, ensuring those with cirrhosis complicated by HE receive timely and appropriate treatment.

Little is known about the interdependence of psychological distress among patients with decompensated cirrhosis and their caregivers.

In this cross-sectional study, we examined the interdependence of psychological distress (Hospital Anxiety and Depression Scale) among 127 patient-caregiver dyads using Actor-Partner Interdependence Modeling.

Among dyads, 26% had both partners reporting clinically significant anxiety and 18% reporting clinically significant depression. Caregiver anxiety significantly predicted patient depression (standardized β = 0.18, P = 0.03).

Psychological distress was prevalent and interdependent among dyads. These results underscore the need to develop interventions to reduce psychological distress in both patients with decompensated cirrhosis and their caregivers.

In this study, we focused on gaining an in-depth understanding on the attitudes and perceptions of hepatology healthcare professionals toward screening for cryptogenic hepatic encephalopathy (CHE), with the goal of providing references for the scientific and standardized implementation of CHE screening.

Based on the phenomenological research method, semi-structured in-depth interviews with nine medical professionals were conducted in March 2023 at the department of hepatology of a tertiary hospital in Taizhou city. The collected data was then integrated and analyzed using the Colaizzi seven-step method.

Three main themes and seven sub-themes were identified: Inadequate knowledge of relevant information (inadequate knowledge of CHE, inadequate knowledge of neuropsychological test tools for CHE); positive attitudes toward screening for cirrhosis CHE; and screening factors (limited human resources, lack of stringent rules from the management, inability to properly use neuropsychological test tools, lack of cooperation from patients and their families, and lack of auxiliary means of screening).

Hepatology medical care personnel had a favorable outlook on CHE screening, however there is room for improvement in both their level of knowledge and clinical work. As a result the administrative departments of hospitals should focus on the factors affecting the clinical work of hepatology medical care personnel and formulate corresponding countermeasures. Emphasis should be placed on the screening and management of CHE for early recognition, early intervention, improvement of quality of life, and effective prevention of hepatic encephalopathy.

This study investigates serum markers for short-term prognosis in hepatic encephalopathy patients.

Patients with hepatic encephalopathy face elevated mortality rates and bleak prognoses. However, effective prognostic models or indicators are lacking. This study aims to explore serum markers for predicting short-term prognosis in these patients.

We conducted a retrospective analysis of 552 patients with hepatic encephalopathy, categorizing 429 individuals meeting exclusion criteria into normal and high activated partial thromboplastin time (APTT) groups. We assessed 12-day and 25-day survival rates using Kaplan-Meier analysis and Cox regression models to examine associations between groups and outcomes.

Upon comparing baseline characteristics, the high APTT group exhibited significant disparities in acute kidney injury, sepsis, coagulation disorders, and ascites (p < 0.05). In the multivariate COX regression model, the hazard ratios [HRs; 95% confidence interval (CI)] of 12- and 25-day mortality were 1.012 (1.001, 1.022, p = 0.033) and 1.010 (1.002, 1.018, p = 0.013), respectively. We discovered that APTT demonstrated an independent association with prognosis. Our findings revealed that the ability of APTT to predict short-term prognosis surpasses that of the traditional MELD model. Regarding 12- and 25-day survival, Kaplan-Meier survival curves from these groups demonstrated a lower survival probability for patients in the high APTT group than the normal group (log-rank p < 0.05). The results of subgroup analysis and interaction analysis indicate that APTT is not influenced by other confounding factors.

A prolonged APTT suggests a poorer short-term prognosis in patients with hepatic encephalopathy.

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.

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.

Malnutrition in cirrhosis is associated with poor outcomes, leading to guidelines for a high protein, low sodium diet; however, there is no guidance regarding the implementation of diet education in clinical practice.

A mixed methods study enrolled 21 patients with cirrhosis and their caregivers. Semi-structured interviews on barriers and facilitators of dietary education and adherence were conducted. Demographic and clinical data were obtained, along with quantitative measures of dietary adherence, including 24-h food recall and spot urine sodium. Combined deductive and inductive coding was used to identify qualitative themes, along with a quantitative assessment of interviews. Quantitative data was reported using descriptive statistics with frequencies, mean and confidence intervals.

Participants were mostly male (16/21) with a mean age 57.8 years (SE 2.8) and MELD-Na 9 (SE 1.2). 4 themes emerged: 1. More than 50% of participants and caregivers endorsed no or inadequate diet education 2. They reported mostly negative experiences with dietary adherence with largest impact on social life 3. Facilitators of adherence included the presence of household support and fear of complications of cirrhosis 4. Overwhelmingly desired non-generic handouts and information. Dietary adherence was poor with only one participant meeting protein and sodium requirements based on food recall. Four participants who adhered to < 2000 mg sodium had inadequate daily caloric intake.

Dietary education is inadequate, and adherence to dietary recommendations is poor in patients with cirrhosis. Future studies should use these barriers and facilitators for intervention development.

Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension.

This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema.

This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.

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.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency with symptoms ranging from slight cognitive changes detectable only by neuropsychiatric testing to coma. Up to 60% of patients with cirrhosis have mild forms of HE and 35% will at some point experience overt HE. Even in its milder forms, HE impacts the patient's daily routines, self-sufficiency, quality of life, and, thereby, socio-economic status. HE is a condition affecting the whole household including formal and informal caregivers, who carry a heavy burden. Early identification, prophylaxis, and treatment of HE are essential for relieving patients and informal caregivers.

Various chronic liver diseases inevitably end up with cirrhosis of the liver, and this comes with a whole range of haematological complications. Therefore, this detailed review has discussed pathophysiology, clinical manifestations, diagnostic measures, and treatment plans for these anomalies. Closely related are conditions such as anaemia, thrombocytopenia, coagulopathy, leukopenia, and haemolytic disorders, which are known to contribute to morbidity and mortality in cirrhotic patients significantly. Therefore, we need to understand the causes of these problems to find ways of helping our patients better. For this reason, multidisciplinary management will be key in ensuring proper monitoring, timely intervention, and preventive measures for haematological abnormalities in cirrhosis. Additionally, there have been tremendous advancements in therapeutic options, like adjunctive therapies or haematopoietic growth factors, which hold much promise regarding patient outcomes. This article emphasizes the proactive management of haematological complications associated with cirrhosis while highlighting the need for further research coupled with collaboration aimed at strengthening prevention strategies, diagnostic methods, and curative interventions.

Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics.

We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms.

We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

Parental depression is a significant problem that negatively affects parents' welfare and influences family dynamics, children's academic and health behaviors, and mental health. However, there is limited evidence regarding the impact of the parental depression into the children's' psychological and physical wellbeing on Asian cultures. This study examined the psychological burdens and health behaviors of adolescent children with parents with depression in the Republic of Korea.

We conducted a cross-sectional study using data from the Korean National Health and Nutrition Examination Survey (KNHANES) spanning 2013 to 2021 to compare health behaviors and mental health outcomes between 203 adolescent children with parents diagnosed with depression and 3,856 control adolescents aged 12-19 years.

Following multivariate adjustments, the risk of depressive mood for more than two weeks was significantly increased in boys with parental depression (adjusted Odds Ratio [aOR] = 2.05, 95% Confidence Interval [CI] = 1.91-3.52) and adolescents with parents with moderate-to-severe depression (aOR = 2.60, 95% CI = 1.17-5.77). Adolescents with parental depression reported significantly worse subjective health status (aOR = 1.88, 95% CI = 1.05-3.36) and higher stress levels (aOR = 1.91, 95% CI = 1.33-2.76). Additionally, when parental depression was present and the time since depression diagnosis was more than five years, adolescents with parental depression exhibited even poorer subjective health status and higher stress levels.

The study found that adolescents whose parents experienced depression had poorer mental health than those whose parents did not have mental health issues. These findings emphasize the importance of providing support for the mental health of adolescents in families affected by parental depression.

Hepatic encephalopathy-a common and debilitating complication of cirrhosis-results in major health care burden on both patients and caregivers through direct and indirect costs. In addition to risk of falls, inability to work and drive, patients with hepatic encephalopathy often require hospital admission (and often readmission), and many require subacute care following hospitalization. The costs and psychological impact of liver transplantation often ensue. As the prevalence of chronic liver disease increases throughout the United States, the health care burden of hepatic encephalopathy will continue to grow.

Hepatic encephalopathy is a medical condition that stems from liver dysfunction, leading to the accumulation of toxins in the bloodstream. This can result in cognitive impairments, mood changes, and motor dysfunction. Its social impact includes challenges in employment, relationships, and daily functioning for affected individuals. Stigma and misunderstanding around the condition can further exacerbate the difficulties faced by both patients and their caregivers. Efforts to raise awareness, improve medical management, and provide support systems can help mitigate the social impact of hepatic encephalopathy.

Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population.

We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission.

Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04).

For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction.

In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann-Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses.

Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P < 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = -0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = -0.379, P = 0.033).

Metabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.

Cirrhosis patients have poor health-related quality of life (HRQoL). To enhance medical care and therapeutic approaches, it is crucial to identify factors that alter HRQoL in patients with cirrhosis. The present study aims to identify the potential factors affecting and promoting HRQoL in patients with liver cirrhosis. Four databases were extensively searched, including PubMed, Scopus, Embase, and Google Scholar. All original articles with liver cirrhosis and factor-altering HRQoL were included. The present study showed that elderly age, female gender, low family income, low body mass index (BMI), presence of anxiety and depression, presence of cirrhosis complications including ascites, hepatic encephalopathy (HE), and abnormal endoscopic findings, high disease severity score, presence of sarcopenia, disturbed sleep pattern, muscle cramps, poor sexual health, and increased levels of bilirubin, prothrombin time, and albumin-bilirubin ratio were the significant factors associated with lower HRQoL scores. Meanwhile, physical exercise, liver transplant, stem cell therapy, mindfulness, and the use of probiotics, rifaximin, and lactulose were associated with increased HRQoL scores. The present study recommends more prospective or randomized control trials with interventions including health education, yoga, psychotherapy, and other potential factors promoting HRQoL in patients with liver cirrhosis. The present study also emphasizes that the treating physician should consider taking HRQoL into account when prescribing medical therapy.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension and its' complications in liver cirrhosis, yet the development of hepatic encephalopathy (HE) remains a significant concern. This review covers the reported incidence, risk factors, and management strategies for post-TIPS HE over the past decade. Incidence varies widely (7-61%), with factors like age, liver function, hyponatremia, and spontaneous portosystemic shunts influencing risk. Procedural aspects, including TIPS timing, indication, and stent characteristics, also contribute. Pharmacological prophylaxis with lactulose and rifaximin shows promise, but current evidence is inconclusive. Procedural preventive measures, such as shunt embolization and monitoring portal pressure gradients, are explored. Treatment involves pharmacological options like lactulose and rifaximin, and procedural interventions like stent diameter reduction. Ongoing studies on novel predictive markers and emerging treatments, such as faecal microbiota transplant, reflect the evolving landscape in post-TIPS HE management. This concise review provides clinicians with insights into the multifaceted nature of post-TIPS HE, aiding in improved risk assessment, prophylaxis, and management for patients undergoing TIPS procedures.

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of cirrhosis and other chronic liver diseases (COCLDs).

To conduct a comprehensive and comparable updated analysis of the global, regional, and national burden of COCLDs due to NAFLD in 204 countries and territories from 1990 and 2019 by age, sex, and sociodemographic index.

Data on COCLDs due to NAFLD were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Numbers and age-standardized prevalence, death, and disability-adjusted life years (DALYs) were estimated through a systematic analysis of modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. The estimated annual percentage change was used to determine the burden trend.

In 2019, the global age-standardized prevalence rate of COCLDs due to NAFLD was 15022.90 per 100000 population [95% uncertainty interval (UI): 13493.19-16764.24], which increased by 24.51% (22.63% to 26.08%) from 1990, with an estimated annual percentage change of 0.78 (95% confidence interval: 0.74-0.82). In the same year, however, the age-standardized death rate and age-standardized DALYs per 100000 population were 1.66 (95%UI: 1.20-2.17) and 43.69 (95%UI: 31.28-58.38), respectively. North Africa and the Middle East had the highest prevalence rates of COCLDs due to NAFLD. The death rate increased with age up to the 95+ age group for both sexes. Males had higher numbers of prevalence, death rate, and DALYs than females across all age groups before the 65-69 age group. The sociodemographic index was negatively correlated with the age-standardized DALYs.

Globally, the age-standardized prevalence rate has increased during the past three decades. However, the age-standardized death rate and age-standardized DALYs decreased. There is geographical variation in the burden of COCLDs due to NAFLD. It is strongly recommended to improve the data quality of COCLDs due to NAFLD across all countries and regions to facilitate better monitoring of the burden of COCLDs due to NAFLD.

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.

Hepatic encephalophathy (HE) is a neuropsychiatric syndrome with a prevalence in the cirrhotic population ranging from 20 to 80%. HE is a cause of inappropriate hospitalization, caregiver burdening and increased social costs. There is need to create dedicated care pathways to better manage patients and support family caregivers. The data used for the preparation of this diagnostic therapeutic assistance path (DTAP) are based on a detailed analysis of the scientific literature published before June 30, 2022 (PubMed, Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted in particular the guidelines/ position papers of International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), Italian Association for the Study of the Liver (AISF), European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), Italian Society on Alcohol (Società Italiana di Alcologia [SIA]) and other relevant papers. DTAP was created based on the most recent recommendations of the international scientific literature. The present DTAP highlight the need for a multidisciplinary activity integrated with territorial medicine in close connection with caregivers. This guarantees improved therapeutic adherence, hospital readmission reduction, improved quality of life for patients and caregivers and a significant reduction in costs.

Introduction: Patients with cirrhosis have a decreased quality of life due to decompensations of their underlying disease. While liver transplantation (LT) has improved outcomes and quality of life for patients with cirrhosis, many patients die or are delisted before transplant. Despite high morbidity and mortality, palliative care (PC) services are underutilized for patients with cirrhosis. Methods: To evaluate current PC and advance care practices at LT centers, a survey was designed and sent to 115 U.S. LT centers. Results: Forty-two surveys were completed (37% response rate) with representation from all United Network for Organ Sharing regions. Nineteen institutions (46.3%) reported 100 or fewer waitlisted patients, while 22 (53.6%) reported more than 100. Twenty-five institutions (59.5%) reported 100 or fewer transplants performed in the last year and 17 (40.5%) reported more than 100. Nineteen transplant centers (45.2%) require patients to discuss advance directives as part of the LT evaluation, while 23 (54.8%) do not. Only 5 centers (12.2%) reported having a dedicated PC provider as part of their transplant team and only 2 reported requiring patients to meet with a PC provider as part of the LT evaluation process. Discussion: This study shows many LT centers do not engage their patients in advance directive discussions and highlights the underutilization of PC services in the LT evaluation process. Our results also show minimal advancement in the collaboration between PC and transplant hepatology over the last decade. Encouraging or requiring LT centers to hold advance directive discussions and incorporate PC providers into the transplant team is a recommended area for improvement.

Patient caregivers experience burden and distress that negatively impacts health-related quality of life (HRQOL). Mindfulness may alleviate caregiver burden but randomized trials of mindfulness activities on caregiver burden and distress are lacking.

Caregivers for patients with advanced liver disease were recruited from the Universities of Michigan and Pennsylvania (12/2019-12/2021) and followed for 8 weeks. Participants were randomized 1:1:1 to: written emotional disclosure for 4 weeks, resilience training for 4 weeks, or control (no active intervention). All completed assessments at baseline, week 4 and 8. The primary outcome was change in the Zarit Caregiver Burden Index-12 (ZBI) at week 8. Secondary outcomes included changes at week 4 and 8 in the ZBI, distress thermometer (DT), HRQOL visual analog scale (VAS), and caregiver captivity index (CCI).

Eighty seven caregivers were enrolled, 59(72%) completed the study. In unadjusted analyses at week 4, the burden measured by ZBI was not significantly different between arms, increasing by 0.6 ± 5.7 and 2.5 ± 5.2 points, for the written emotional disclosure and resilience training study arms, respectively, and by 2.9 ± 6.1 points in the control arm. At week 8, the non-significant ZBI change was - 1.0 ± 8.9, 2.8 ± 6.1, and 1.5 ± 7.4 for written emotional disclosure, resilience training, at week 8, respectively. The DT and VAS worsened in all arms, however, it worsened the least in the written emotional disclosure arm. In analyses adjusted for differences in baseline characteristics, the ZBI declined by - 4.21 ± 2.03(p = 0.04) in the emotional disclosure arm at week 4. This decrease was attenuated week 8, - 1.13 ± 2.6(p = 0.67). There were no significant differences in secondary outcomes save for resilience training reducing the CCI at week 4 by 1.36 ± 0.67(p = 0.04).

Written emotional disclosure may reduce caregiver burden in the short term among caregivers for patients with cirrhosis.

NCT04205396.

Health literacy is low among patients with chronic liver disease (CLD) and associated with poor health outcomes and increased health care use. Lucy LiverBot, an artificial intelligence chatbot was created by a multidisciplinary team at Monash Health, Australia, to improve health literacy and self-efficacy in patients with decompensated CLD.

The aim of this study was to explore users' experience with Lucy LiverBot using an unmoderated, in-person, qualitative test.

Lucy LiverBot is a simple, low cost, and scalable digital intervention, which was at the beta prototype development phase at the time of usability testing. The concept and prototype development was realized in 2 phases: concept development and usability testing. We conducted a mixed methods study to assess usability of Lucy LiverBot as a tool for health literacy education among ambulatory and hospitalized patients with decompensated CLD at Monash Health. Patients were provided with free reign to interact with Lucy LiverBot on an iPad device under moderator observation. A 3-part survey (preuser, user, and postuser) was developed using the Unified Acceptance Theory Framework to capture the user experience.

There were 20 participants with a median age of 55.5 (IQR 46.0-60.5) years, 55% (n=11) of them were female, and 85% (n=17) of them were White. In total, 35% (n=7) of them reported having difficulty reading and understanding written medical information. Alcohol was the predominant etiology in 70% (n=14) of users. Participants actively engaged with Lucy LiverBot and identified it as a potential educational tool and device that could act as a social companion to improve well-being. In total, 25% (n=5) of them reported finding it difficult to learn about their health problems and 20% (n=4) of them found it difficult to find medical information they could trust. Qualitative interviews revealed the conversational nature of Lucy LiverBot was considered highly appealing with improvement in mental health and well-being reported as an unintended benefit of Lucy LiverBot. Patients who had been managing their liver cirrhosis for several years identified that they would be less likely to use Lucy LiverBot, but that it would have been more useful at the time of their diagnosis. Overall, Lucy LiverBot was perceived as a reliable and trustworthy source of information.

Lucy LiverBot was well received and may be used to improve health literacy and address barriers to health care provision in patients with decompensated CLD. The study revealed important feedback that has been used to further optimize Lucy LiverBot. Further acceptability and validation studies are being undertaken to investigate whether Lucy LiverBot can improve clinical outcomes and health related quality of life in patients with decompensated CLD.

Liver disease is associated with substantial morbidity and mortality, likely incurring financial distress (i.e. healthcare affordability and accessibility issues), although long-term national-level data are limited.

Using the National Health Interview Survey from 2004 to 2018, we categorised adults based on report of liver disease and other chronic conditions linked to mortality data from the National Death Index. We estimated age-adjusted proportions of adults reporting healthcare affordability and accessibility issues. Multivariable logistic regression and Cox regression were used to assess the association of liver disease with financial distress and financial distress with all-cause mortality, respectively.

Among adults with liver disease (n = 19,407) vs. those without liver disease (n = 996,352), those with cancer history (n = 37,225), those with emphysema (n = 7,937), and those with coronary artery disease (n = 21,510), the age-adjusted proportion reporting healthcare affordability issues for medical services was 29.9% (95% CI 29.7-30.1%) vs. 18.1% (95% CI 18.0-18.3%), 26.5% (95% CI 26.3-26.7%), 42.2% (95% CI 42.1-42.4%), and 31.6% (31.5-31.8%), respectively, and for medications: 15.5% (95% CI 15.4-15.6%) vs. 8.2% (95% CI 8.1-8.3%), 14.8% (95% CI 14.7-14.9%), 26.1% (95% CI 26.0-26.2%), and 20.6% (95% CI 20.5-20.7%), respectively. In multivariable analysis, liver disease (vs. without liver disease, vs. cancer history, vs. emphysema, and vs. coronary artery disease) was associated with inability to afford medical services (adjusted odds ratio [aOR] 1.84, 95% CI 1.77-1.92; aOR 1.32, 95% CI 1.25-1.40; aOR 0.91, 95% CI 0.84-0.98; and aOR 1.11, 95% CI 1.04-1.19, respectively) and medications (aOR 1.92, 95% CI 1.82-2.03; aOR 1.24, 95% CI 1.14-1.33; aOR 0.81, 95% CI 0.74-0.90; and aOR 0.94, 95% CI 0.86-1.02, respectively), delays in medical care (aOR 1.77, 95% CI 1.69-1.87; aOR 1.14, 95% CI 1.06-1.22; aOR 0.88, 95% CI 0.79-0.97; and aOR 1.05, 95% CI 0.97-1.14, respectively), and not receiving the needed medical care (aOR 1.86, 95% CI 1.76-1.96; aOR 1.16, 95% CI 1.07-1.26; aOR 0.89, 95% CI 0.80-0.99; aOR 1.06, 95% CI 0.96-1.16, respectively). In multivariable analysis, among adults with liver disease, financial distress (vs. without financial distress) was associated with increased all-cause mortality (aHR 1.24, 95% CI 1.01-1.53).

Adults with liver disease face greater financial distress than adults without liver disease and adults with cancer history. Financial distress is associated with increased risk of all-cause mortality among adults with liver disease. Interventions to improve healthcare affordability should be prioritised in this population.

Adults with liver disease use many medical services, but long-term national studies regarding the financial repercussions and the effects on mortality for such patients are lacking. This study shows that adults with liver disease are more likely to face issues affording medical services and prescription medication, experience delays in medical care, and needing but not obtaining medical care owing to cost, compared with adults without liver disease, adults with cancer history, are equally likely as adults with coronary artery disease, and less likely than adults with emphysema-patients with liver disease who face these issues are at increased risk of death. This study provides the impetus for medical providers and policymakers to prioritise interventions to improve healthcare affordability for adults with liver disease.

Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome. Often, HE causes cognitive and motor dysfunctions due to an acute or chronic insufficiency of the liver or a shunting between the hepatic portal vein and systemic vasculature. Liver damage induces peripheral changes, such as in the metabolism and peripheral inflammatory responses that trigger exacerbated neuroinflammation. In experimental models, anti-inflammatory strategies have demonstrated neuroprotective effects, leading to a reduction in HE-related cognitive and motor impairments. In this scenario, a growing body of evidence has shown that peripheral and central nervous system inflammation are promising preclinical targets. In this review, we performed an overview of FDA-approved drugs and natural compounds which are used in the treatment of other neurological and nonneurological diseases that have played a neuroprotective role in experimental HE, at least in part, through anti-inflammatory mechanisms. Despite the exciting results from animal models, the available data should be critically interpreted, highlighting the importance of translating the findings for clinical essays.

Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non-absorbable antibiotic that inhibits urease-producing bacteria and reduces absorption of dietary and bacterial ammonia.

To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non-absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non-absorbable disaccharide.

We searched the Cochrane Hepato-Biliary Group Clinical Trials Register, CENTRAL, MEDLINE, Embase, three other databases, the reference lists of identified papers, and relevant conference proceedings. We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials. Searches were performed to January 2023.

We included randomised clinical trials assessing prevention or treatment of hepatic encephalopathy with rifaximin alone, or with a non-absorbable disaccharide, versus placebo/no intervention, or a non-absorbable disaccharide alone.

Six authors independently searched for studies, extracted data, and validated findings. We assessed the design, bias risk, and participant/intervention characteristics of the included studies. We assessed mortality, serious adverse events, health-related quality of life, hepatic encephalopathy, non-serious adverse events, blood ammonia, Number Connection Test-A, and length of hospital stay.

We included 41 trials involving 4545 people with, or at risk for, developing hepatic encephalopathy. We excluded 89 trials and identified 13 ongoing studies. Some trials involved participants with more than one type of hepatic encephalopathy or more than one treatment comparison. Hepatic encephalopathy was classed as acute (13 trials), chronic (7 trials), or minimal (8 trials), or else participants were considered at risk for its development (13 trials). The control groups received placebo (12 trials), no/standard treatment (1 trial), or a non-absorbable disaccharide (14 trials). Eighteen trials assessed rifaximin plus a non-absorbable disaccharide versus a non-absorbable disaccharide alone. We classified 11 trials as at high risk of overall bias for mortality and 28 for non-mortality outcomes, mainly due to lack of blinding, incomplete outcome data, and selective reporting. Compared to placebo/no intervention, rifaximin likely has no overall effect on mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.50 to 1.38; P = 48, I2 = 0%; 13 trials, 1007 participants; moderate-certainty evidence), and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.99, 95% CI 0.49 to 1.97; P = 0.97, I2 = 0%; 10 trials, 786 participants; low-certainty evidence). However, there is likely a reduction in the overall risk of mortality when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.69, 95% CI 0.55 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) = 22; P = 0.001, I2 = 0%; 14 trials, 1946 participants; moderate-certainty evidence). There is likely no effect on the overall risk of serious adverse events when comparing rifaximin to placebo/no intervention (RR 1.05, 95% CI 0.83 to 1.32; P = 68, I2 = 0%; 9 trials, 801 participants; moderate-certainty evidence) and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.97, 95% CI 0.66 to 1.40; P = 85, I2 = 0%; 8 trials, 681 participants; low-certainty evidence). However, there was very low-certainty evidence that use of rifaximin plus a non-absorbable disaccharide may be associated with a lower risk of serious adverse events than use of a non-absorbable disaccharide alone (RR 0.66, 95% CI 0.45 to 0.98; P = 0.04, I2 = 60%; 7 trials, 1076 participants). Rifaximin likely results in an overall effect on health-related quality of life when compared to placebo/no intervention (mean difference (MD) -1.43, 95% CI -2.87 to 0.02; P = 0.05, I2 = 81%; 4 trials, 214 participants; moderate-certainty evidence), and may benefit health-related quality of life in people with minimal hepatic encephalopathy (MD -2.07, 95% CI -2.79 to -1.35; P < 0.001, I2 = 0%; 3 trials, 176 participants). The overall effect on health-related quality of life when comparing rifaximin to non-absorbable disaccharides is very uncertain (MD -0.33, 95% CI -1.65 to 0.98; P = 0.62, I2 = 0%; 2 trials, 249 participants; very low-certainty evidence). None of the combined rifaximin/non-absorbable disaccharide trials reported on this outcome. There is likely an overall beneficial effect on hepatic encephalopathy when comparing rifaximin to placebo/no intervention (RR 0.56, 95% CI 0.42 to 0.77; NNTB = 5; P < 0.001, I2 = 68%; 13 trials, 1009 participants; moderate-certainty evidence). This effect may be more marked in people with minimal hepatic encephalopathy (RR 0.40, 95% CI 0.31 to 0.52; NNTB = 3; P < 0.001, I2 = 10%; 6 trials, 364 participants) and in prevention trials (RR 0.71, 95% CI 0.56 to 0.91; NNTB = 10; P = 0.007, I2 = 36%; 4 trials, 474 participants). There may be little overall effect on hepatic encephalopathy when comparing rifaximin to non-absorbable disaccharides (RR 0.85, 95% CI 0.69 to 1.05; P = 0.13, I2 = 0%; 13 trials, 921 participants; low-certainty evidence). However, there may be an overall beneficial effect on hepatic encephalopathy when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.58, 95% CI 0.48 to 0.71; NNTB = 5; P < 0.001, I2 = 62%; 17 trials, 2332 participants; low-certainty evidence).

Compared to placebo/no intervention, rifaximin likely improves health-related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health-related quality of life, or hepatic encephalopathy compared to non-absorbable disaccharides. However, when used in combination with a non-absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high-quality trials are needed.

(1) Background: Little is known about facilitators of and barriers to palliative care referral for people with hepatocellular carcinoma (HCC). The objective of this study is to identify facilitators and barriers of palliative care referral described by HCC-treating clinicians. (2) Methods: Semi-structured interviews (n = 16) were conducted with HCC-treating clinicians at two centers, focusing on referral patterns, palliative care needs, and disease course. A code book was created, axial coding was used to code all interviews, and selective coding was used to identify facilitators and barriers of palliative care referral. (3) Results: Facilitators included helpfulness at times of transition; help with management of certain symptoms; provision of psychosocial support; and positive experiences with referral. Barriers included feasibility concerns; lack of information about palliative care and who is appropriate; lack of symptoms requiring outside referral; and concerns that palliative care conveys loss of hope. (4) Conclusions: Participants noted the helpfulness of palliative care at specific points in the disease trajectory and cited barriers related to feasibility, lack of need, lack of awareness, and loss of hope. The results show actionable issues that can be addressed in future research to leverage the benefits of and overcome the barriers to palliative care for people with HCC.

Real-world data on the therapeutic management of hepatic encephalopathy (HE) patients are limited. The aim of this study was to evaluate the HE medications prescribed in an Italian cohort of HE patients post-discharge and to assess the real-world rifaximin adherence and persistence over 1 year. An observation retrospective study was conducted using data retrieved from outpatient pharmaceutical databases and hospital discharge records of the Campania region. For all subjects hospitalized for HE during 2019 (cohort 1), the HE medications prescribed within 60 days after discharge were evaluated. Adherence (proportion of days covered, PDC) and persistence were estimated for rifaximin 550 mg incident users over 1 year (cohort 2). Patients with PDC ≥80% were considered adherents. Persistence was defined as the period of time from the first rifaximin prescription to the date of discontinuation. Discontinuation was assessed using the permissible gap method. In cohort 1, 544 patients were identified; 58.5% received rifaximin while 15.6% only received non-absorbable disaccharides and 25.9% did not receive any HE medications. In cohort 2, 650 users were selected; only 54.5% were adherents and 35% were persistent users at 1 year. This real-world study highlights that quality improvement in therapeutic management is needed to potentially improve the outcomes of HE patients.

Hepatic encephalopathy (HE) in cirrhosis is an extremely challenging complication for patients and care partners. To identify potentially modifiable factors to enhance HE self-management strategies, we conducted a synthesis of quantitative and qualitative research about real-world HE behaviours, knowledge, and experiences.

Using the EPPI-Centre's mixed methods synthesis procedure, a systematic literature search in five databases was completed; methods of selected articles underwent critical appraisal followed by descriptive analysis and coded line-by-line of content. Through refutational translation, the findings from the quantitative and qualitative syntheses were juxtaposed to highlight congruencies, incongruencies, or gaps. These findings informed generation of cross-analytical themes that were transformed into action statements.

The quantitative narrative review of synthesis (n = 17) generated four themes (patients had low awareness of HE and low treatment adherence rates, physicians had a non-uniform approach to non-pharmaceutical therapies). Meta-aggregation of qualitative data from six articles yielded three themes (patients and care partners had low levels of HE awareness, were unfamiliar with HE self-management, and were adherent to treatments). Comparison of findings revealed three congruencies, two gaps, and one incongruency. The combined synthesis yielded two self-management themes: universal patient-oriented cirrhosis HE education and ensuring each health care encounter systematically addresses HE to guarantee health care is continuously modified to meet their needs.

By drawing on elements of Bloom's Taxonomy and distributed knowledge networks, deliberate patient-oriented HE messaging at all health care encounters is greatly needed to improve health outcomes and reduce care burdens related to HE.

Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI.

A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation.

172 patients (age 57 ± 13, model of end-stage liver disease [MELD]-sodium 22 ± 8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P = 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality.

HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.

Although the association between Helicobacter pylori (H. pylori) infection and hepatic encephalopathy (HE) has been confirmed through some research, the results of these relevant studies still remain controversial. We conducted an updated meta-analysis based on published studies to address this issue.

A systematic search was conducted, reviewing all studies about the association between H. pylori infection and HE, through November 2021. The outcome measures were presented as odds ratios (ORs) with 95% confidence intervals (CIs).

In total, 13 studies provided data from 2784 subjects. H. pylori infection increased the risk of HE by 32% (OR = 2.32, 95% CI: 1.78-3.04). The effect became greater after hepatic encephalopathy was divided into overt HE and minimal hepatic encephalopathy (MHE) (HE OR = 2.66, 95% CI: 2.01-3.51, MHE OR = 1.74, 95% CI: 1.10-2.76). After H. pylori eradication, the risk of HE was reduced by 64%.

H. pylori infection is significantly associated with HE, and the infection rate of H. pylori also increases with the severity of HE. Eradication of H. pylori has a protective effect on HE. Therefore, it is necessary to eradicate H. pylori in HE treatments.

Hepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE.

We prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT).

During follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01-1.06), HE (HR 1.67, 95% CI 1.08-2.56), ascites (HR 2.56, 95% CI 1.55-4.23), and sodium levels (HR 0.94, 95% CI 0.90-0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39-18.49) and BMI (HR 0.86, 95% CI 0.75-0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission.

In patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.