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Abstract Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Abstract Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched men [56 years, healthy control, compensated, early (ascites and lactulose use) and advanced decompensated cirrhosis (ascites and rifaximin use)]. Cell type proportions, differential gene expressions, cell-type specific pathway analysis using IPA, and cellular crosstalk dynamics were compared. Stem cells, enterocytes and Paneth cells were lowest in advanced decompensation. Immune cells like naive CD4 + T cells were lowest while ITGAE + cells were highest in advanced decompensation patients. MECOM had lowest expression in stem cells in advanced decompensation. Defensin and mucin sulfation gene (PAPSS2) which can stabilize the mucus barrier expression were lowest while IL1, IL6 and TNF-related genes were significantly upregulated in the enterocytes, goblet, and Paneth cells in decompensated subjects. IPA analysis showed higher inflammatory pathways in enterocytes, stem, goblet, and Paneth cells in decompensated patients. Cellular crosstalk analysis showed that desmosome, protease-activated receptors, and cadherin-catenin complex interactions were most perturbed in decompensated patients. In summary, the snRNAseq of the human terminal ileum in 4 subjects (1 control and three cirrhosis) identified multidimensional alteration in the intestinal barrier with lower stem cells and altered gene expression focused on inflammation, mucin sulfation and cell–cell interactions with cirrhosis decompensation.

Abstract Background Practical and feasible methods for matching implementation strategies to diagnosed barriers of evidence-based interventions in real-world contexts are lacking. This evaluation compared actual implementation strategies applied with those recommended by an expert opinion-based tool to improve guideline-concordant cirrhosis care in a Veterans Health Administration national learning collaborative effort. Methods This convergent parallel mixed-methods study aimed to (1) identify pre-implementation Consolidated Framework for Implementation Research (CFIR) barriers to cirrhosis care through focus groups with frontline providers, (2) generate 20 recommended strategies using focus group identified barriers entered into the CFIR-Expert Recommendations for Implementing Change (ERIC) Implementation Strategy Matching Tool, (3) survey providers over two consecutive years on the actual use of 73 ERIC strategies and determine strategy effectiveness, (4) compare actual versus recommended strategy use, and (5) compare actual versus expected barriers by reverse applying the CFIR-ERIC Matching Tool. Results Eighteen semi-structured focus groups were conducted with 197 providers representing 95 VA sites to identify barriers to quality improvement, including cirrhosis care complexity, clarity of national goals, and local leadership support. The CFIR-ERIC Matching Tool recommended strategies such as assessing for readiness and needs, promoting adaptability, building local groups, preparing champions, and working with opinion leaders and early adopters. Subsequent strategy surveys found that sites used the top 20 “recommended” strategies no more frequently than other strategies. However, 14 (70%) of the top recommended strategies were significantly positively associated with cirrhosis care compared to 48% of actual strategies. Reverse CFIR-ERIC matching found that the strategies most used in the first year corresponded to the following barriers: opinion leaders, access to knowledge and information, and resources. The strategies most frequently employed in the second year addressed barriers such as champions, cosmopolitanism, readiness for implementation, relative priority, and patient needs and resources. Strategies used in both years were those that addressed adaptability, trialability, and compatibility. Conclusions This study is among the first to empirically evaluate the relationship between CFIR-ERIC Matching Tool recommended strategies and actual strategy selection and effectiveness in the real world. We found closer connections between recommended strategies and strategy effectiveness compared to strategy frequency, suggesting validity of barrier identification, and application of the expert-informed tool.

Gut microbiota composition is altered in patients with alcohol use disorder, and fecal microbiota transplant reduced alcohol craving in patients with alcohol use disorder and liver cirrhosis in a phase 1 clinical trial. Here the authors used stool samples collected in the trial to report that this phenotype is transmissible via microbial transfer to germ free mice, as assessed by reduced ethanol acceptance, intake and preference.

Abstract Driving is independently affected by cirrhosis and hepatic encephalopathy (HE) and alcohol/substance use, but their concomitant impact is unclear. We aimed to determine the impact of alcohol and other substances on driving‐simulator performance in cirrhosis with and without HE. Outpatients with cirrhosis and controls underwent cognitive testing and driving simulation for the following three conditions: baseline, wearing goggles simulating alcohol intoxication, and wearing goggles simulating opioid/benzodiazepine abuse. Outcomes were number of centerline crossings (CCs) and road‐edge excursions (REEs). We compared controls versus patients with cirrhosis then subjects with cirrhosis with and without HE for all conditions, using generalized linear modeling (GLM). Sixty subjects (17 controls, 43 with cirrhosis [Model for End‐Stage Liver Disease score, 10; 21 subjects with prior HE]) were included. Simulations showed higher CCs and REEs at baseline in patients with cirrhosis with and without HE versus controls. With alcohol‐ and substance abuse‐impairment goggles, CCs increased but REEs decreased in cirrhosis. In the GLM, a time and group interaction was seen (p

Abstract Hepatic encephalopathy (HE) is a serious neurocognitive complication of liver dysfunction, often associated with elevated plasma ammonia. Ornithine phenylacetate (OP), a potent ammonia scavenger, is being evaluated for the treatment of acute/overt HE. The pharmacokinetics and pharmacodynamics of OP in patients with HE were characterized in this phase IIb study (NCT01966419). Adult patients hospitalized with an overt HE episode, cirrhosis, and plasma ammonia above the upper limit of normal (ULN) who failed to improve after 48 hours’ standard care were randomly assigned to continuous intravenous OP (10, 15, or 20 g/day, based on Child–Turcotte–Pugh score) or matching placebo for 5 days. Plasma levels of ornithine and phenylacetic acid (PAA) and plasma/urinary levels of phenylacetylglutamine (PAGN) (primary metabolite of PAA) were regularly assessed; plasma ammonia level was the primary pharmacodynamic variable. PAA demonstrated dose‐dependent pharmacokinetics; ornithine and PAGN levels increased with dose. PAGN urinary excretion represented ~50%–60% of administered PAA across all doses. Mean reduction in plasma ammonia with OP at 3 hours postinfusion was significantly greater versus placebo (p = 0.014); and time to achieve plasma ammonia less than or equal to the ULN was significantly reduced (p = 0.028). Achievement of clinical response based on HE stage was associated with a greater reduction in mean plasma ammonia level (p = 0.009). OP effects on plasma ammonia were consistent with its proposed mechanism of action as a primary ammonia scavenger, with a significant association between reduced plasma ammonia and improvement in HE stage. OP should be further evaluated as a promising treatment for hyperammonemia in patients with overt HE.

Background:. App-based technologies could enhance patient and caregiver communication and provide alerts that potentially reducing readmissions. However, the burden of App alerts needs to be optimized to reduce provider burnout. Aim:. The purpose of this study was to determine subjective and objective burden of using the Patient Buddy App, a health information technology (HIT) on providers in a randomized multicenter trial, who completed a semi-quantitative Likert scale survey regarding training procedures, data and privacy concerns, follow-up details, and technical support. This randomized multicenter trial recruits cirrhosis inpatients and their caregivers, and randomizes them into standard-of-care, HIT (communication only via App) and HIT+visits (App+phone calls/visits) for 30 days after discharge. The alerts are monitored by providers through a central iPad. The reason(s) and number of alerts were recorded as the objective burden. A total of 1442 messages were sent as alerts from the 103 dyads (patient + caregiver) (n=206) randomized to HIT arms. The most common messages related to Hepatic Encephalopathy (HE) (high or low bowel movement=50% or orientation tests=37%). Twelve providers completed the surveys reflecting the following themes—92% and 100%, felt adequately trained and confident about educating the patients and caregivers before roll out of App and had no concerns related to data and privacy; 70%, felt that appropriate time was spent on pursuing reason for data not being logged; 60% each, had issues with availability of adequate technical support and connectivity. Conclusion:. The Patient Buddy App randomized multicenter trial till date shows an overall favorable rating regarding training procedures/education, privacy concerns, and ease of message follow-up, from providers. However, it is important to gauge and address subjective and objective burdens of monitoring human resources in current and future HIT studies to avoid burnout and to ensure successful study completion.

Simple tests of routine data are needed for those with severe acute respiratory syndrome coronavirus 2, which causes corona virus disease 2019 (COVID‐19), to help identify those who may need mechanical ventilation (MV). In this study, we aimed to determine if fibrosis‐4 (FIB‐4) is associated with the need for MV in patients with COVID‐19 and if there is an association to determine the optimal FIB‐4 cutoff. This was a retrospective, national, multiethnic cohort study of adults seen in an ambulatory or emergency department setting who were diagnosed with COVID‐19. We used the TriNetX platform for analysis. Measures included demographics, comorbid diseases, and routine laboratory tests. A total of 4,901 patients with COVID‐19 were included. Patients had a mean age of 56, 48% were women, 42% were obese, 38% were white, 40% were black, 15% had cardiac disease, 39% had diabetes mellitus, 20% had liver disease, and 50% had respiratory disease. The need for MV was 6%. The optimal FIB‐4 cutoff for the need for MV was 3.04 (area under the curve, 0.735), which had sensitivity, specificity, and positive and negative predictive values of 42%, 77%, 11%, and 95%, respectively, with 93% accuracy. When stratified by race, increased FIB‐4 remained associated with the need for MV in both white and black patients. Conclusion: FIB‐4 can be used by frontline providers to identify patients that may require MV.

Obesity and diabetes are strongly associated not only with fatty liver but also cognitive dysfunction. Moreover, their presence, particularly in midlife, is recognized as a risk factor for Alzheimer’s disease (AD). AD, the most common cause of dementia, is increasingly considered as a metabolic disease, although underlying pathogenic mechanisms remain unclear. The liver plays a major role in maintaining glucose and lipid homeostasis, as well as in clearing the AD neuropathogenic factor amyloid‐β (Aβ) and in metabolizing cerebrosterol, a cerebral‐derived oxysterol proposed as an AD biomarker. We hypothesized that liver impairment induced by obesity contributes to AD pathogenesis. We show that the AD triple transgenic mouse model (3xTg‐AD) fed a chow diet presents a hepatic phenotype similar to nontransgenic controls (NTg) at 15 months of age. A high‐fat diet (HFD), started at the age of 6 months and continued for 9 months, until sacrifice, induced hepatic steatosis in NTg, but not in 3xTg‐AD mice, whereas HFD did not induce changes in hepatic fatty acid oxidation, de novo lipogenesis, and gluconeogenesis. HFD‐induced obesity was associated with a reduction of insulin‐degrading enzyme, one of the main hepatic enzymes responsible for Aβ clearance. The hepatic rate of cerebrosterol glucuronidation was lower in obese 3xTg‐AD than in nonobese controls (P

Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one‐time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard‐of‐care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta‐lactamase (OXY/LEN) expression decreased post‐FMT versus baseline. Compared to placebo, patients who were post‐FMT had lower abundance of vancomycin (VanH), beta‐lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta‐lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta‐lactamase, VanW, and VanX) that continued at day 15 (cepA beta‐lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre‐FMT baseline and non‐FMT groups in decompensated cirrhosis.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in individuals without obesity. Here, gut microbiome analysis using a biopsy-proven NAFLD cohort reveal distinct signatures of microbiome-metabolites associated with significant fibrosis in patients with NAFLD without obesity.

Abstract Background Cirrhosis is a rapidly increasing cause of global mortality. To improve cirrhosis care, the Veterans Health Administration (VHA) developed the Hepatic Innovation Team (HIT) Collaborative to support VA Medical Centers (VAMCs) to deliver evidence-based cirrhosis care. This randomized HIT program evaluation aims to develop and assess a novel approach for choosing and applying implementation strategies to improve the quality of cirrhosis care. Methods Evaluation aims are to (1) empirically determine which combinations of implementation strategies are associated with successful implementation of evidence-based practices (EBPs) for Veterans with cirrhosis, (2) manualize these “data-driven” implementation strategies, and (3) assess the effectiveness of data-driven implementation strategies in increasing cirrhosis EBP uptake. Aim 1 will include an online survey of all VAMCs’ use of 73 implementations strategies to improve cirrhosis care, as defined by the Expert Recommendations for Implementing Change taxonomy. Traditional statistical as well as configurational comparative methods will both be employed to determine which combinations of implementation strategies are associated with site-level adherence to EBPs for cirrhosis. In aim 2, semi-structured interviews with high-performing VAMCs will be conducted to operationalize successful implementation strategies for cirrhosis care. These data will be used to inform the creation of a step-by-step guide to tailoring and applying the implementation strategies identified in aim 1. In aim 3, this manualized implementation intervention will be assessed using a hybrid type III stepped-wedge cluster randomized design. This evaluation will be conducted in 12 VAMCs, with four VAMCs crossing from control to intervention every 6 months, in order to assess the effectiveness of using data-driven implementation strategies to improve guideline-concordant cirrhosis care. Discussion Successful completion of this innovative evaluation will establish the feasibility of using early evaluation data to inform a manualized, user-friendly implementation intervention for VAMCs with opportunities to improve care. This evaluation will provide implementation support tools that can be applied to enhance the implementation of other evidence-based practices. Trial registration This project was registered at ClinicalTrials.Gov ( NCT04178096 ) on 4/29/20.

Minimal hepatic encephalopathy (MHE) is underdiagnosed because most clinics refrain from psychometric testing. Diagnostic activities need to go up so patients with MHE can get the treatment their condition requires. The sickness impact profile questionnaire for covert hepatic encephalopathy (SIPCHE) score is based on quality‐of‐life outcomes and has been proposed as a simple, patient‐administered diagnostic score for grade 1 and MHE. Validate the SIPCHE for MHE identification and overt hepatic encephalopathy (OHE) prediction. 110 patients with liver cirrhosis (age 60 years, Model for End‐Stage Liver Disease score of 11.4, 80% blue‐collar) provided information for SIPCHE scoring: gender, age, and four SIP statements: “I do not maintain balance (physically),” “I act irritable or impatient with myself,” “I am not doing any of the usual physical recreation or activities,” and “I am eating much less than usual.” MHE was diagnosed using an abnormal continuous reaction time test and/or portosystemic encephalopathy syndrome test score. Patients were followed for 2.7 years on average. SIPCHE score positivity had high sensitivity (82%) but low specificity (38%) for MHE detection. Patients with an abnormal SIPCHE had a higher incidence of OHE during follow‐up (35% vs. 14%, P = 0.05). OHE prediction sensitivity was 87% and exclusion sensitivity was 85%. The patients with an abnormal SIPCHE had twice as many subsequent episodes of OHE, and despite their high mortality, also a higher risk. An abnormal SIPCHE had a high sensitivity and low specificity for MHE identification. An abnormal SIPCHE was associated with a more than doubled risk of OHE, even with death as a competing event. SIPCHE could be used as a high‐sensitivity, low‐cost, surrogate marker of MHE in clinics without availability of psychometric tests and allow more patients to benefit from anti‐MHE treatment.

Background. Terlipressin is a long acting synthetic analogue of vasopressin, which is used to manage variceal bleeding and hepatorenal syndrome. Terlipressin is being developed to treat refractory ascites in cirrhotic patients who are no longer responsive to diuretic drugs and require repeated paracentesis. This study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of a continuous intravenous (IV) infusion of terlipressin as an outpatient treatment for refractory ascites in patients with advanced liver cirrhosis. Methods. This was an open-label Phase 2a trial. Patients received a continuous IV infusion of terlipressin 2 mg/day escalating to 4 mg/d during an initial 7-day inpatient period, followed by 21 days as outpatients. The PK, safety/tolerability, and effects on the need for and volume of paracentesis were evaluated. Results. Four of 6 patients experienced ≥50% increase in the interval between large volume paracenteses (LVP) with terlipressin. The volume of ascites removed by LVP in the 28-day treatment period was reduced in all patients by ≥30% compared with pretreatment. Terlipressin was rapidly eliminated with a mean half-life of 42.3 minutes, mean clearance of 5.6 mL/min/kg, and volume of distribution of 0.33 L/kg. Average steady state plasma concentrations ranged from 1.69 to 5.55 ng/mL and increased proportionally with increasing dose. Three (50.0%) patients reported treatment-related adverse events, but none were serious. Conclusion. Continuous terlipressin IV infusion improved control of refractory ascites with an acceptable safety and predictable PK profile. Further evaluation of terlipressin is warranted in a randomized controlled trial for treating refractory ascites and related complications of cirrhosis.

BackgroundCirrhosis and hepatic encephalopathy (HE) are linked with an altered gut-liver-brain axis, however, the relative contribution of hepatic vagal innervation is unclear. We aimed to determine the impact of hepatic vagotomy on the gut microbiome, brain, and liver in murine cirrhosis.Methods10–15-week-old male C57BL/6 mice with and without hepatic vagotomy underwent carbon tetrachloride (CCl4) gavage for 8 weeks. Frontal cortex [inflammation, glial/microglial activation, BDNF (brain-derived neurotrophic factor)], liver [histology including inflammation and steatosis, fatty acid synthesis (sterol-responsive binding protein-1) SREBP-1, insulin-induced gene-2 (Insig2) and BDNF], and colonic mucosal microbiota (16srRNA microbial sequencing) were evaluated on sacrifice. Conventional mice with and without cirrhosis were compared to vagotomized counterparts.ResultsConventional control vs. cirrhosis: Cirrhosis resulted in dysbiosis, hepatic/neuro-inflammation with glial/microglial activation, and low brain BDNF vs. controls. Conventional control vs. vagotomy controls: Vagotomized control mice had a lower colonic dysbiosis than conventional mice but the rest of the hepatic/brain parameters were similar. Conventional cirrhosis vs. vagotomized cirrhosis: After vagotomy + cirrhosis, we found lower dysbiosis but continuing neuroinflammation in the absence of glial/microglial activation vs. conventional cirrhosis. Vagotomy + Cirrhosis groups showed higher hepatic steatosis due to higher SREBP1 and low Insig2 protein and altered activation of key genes involved in hepatic lipid metabolism and inflammation. BDNF levels in the brain were higher but low in the liver in vagotomy + cirrhosis, likely a protective mechanism.ConclusionsHepatic vagal innervation affects the gut microbial composition, hepatic inflammation and steatosis, and cortical inflammation and BDNF expression and could be a critical modulator of the gut-liver-brain axis with consequences for HE development.

Background and aims The Veterans Health Administration (VA) cares for over 80,000 Veterans with cirrhosis annually. Given the importance of understanding patient reported outcomes in this complex population, we aimed to assess the associations between attitudes towards care, disease knowledge, and health related quality of life (HRQoL) in a national sample. Methods In this cross-sectional study, we mailed paper surveys to a random sample of Veterans with cirrhosis, oversampling those with decompensated disease. Surveys included the Veterans RAND 12-Item Health Survey (measuring HRQoL) and questions about demographics, characteristics of care, satisfaction with care (“attitudes towards care”), and symptoms of cirrhosis. Those who reported being “unsure” about whether they had decompensation events were defined as “unsure about cirrhosis symptoms” (“disease knowledge”). We used multivariable regression models to assess the factors associated with HRQoL. Results Of 1374 surveys, 551 (40%) completed surveys were included for analysis. Most Veterans (63%) were “satisfied” or “very satisfied” with VA liver care. Patients often self-reported being unsure about whether they had experienced hepatic decompensation events (34%). Overall average physical (PCS) and mental (MCS) component scores of HRQoL were 30±11 and 41±12. In multivariable regression models, hepatic decompensation (PCS:β = -3.8, MCS:β = -2.2), medical comorbidities (β = −-2.0, β = -1.7), and being unsure about cirrhosis symptoms (β = -1.9, β = -3.3) were associated with worse HRQoL, while age (β = 0.1, β = 0.2) and satisfaction with care (β = 0.6; β = 1.6) were associated with significantly better HRQoL. Conclusions Hepatic decompensation, lower satisfaction with care, and being unsure about cirrhosis symptoms were associated with reduced QOL scores in this national cohort.

Proton pump inhibitors (PPIs) reduce gastric acid secretion and modulate gut microbiota composition. Here Llorente et al. show that PPIs induce bacterial overgrowth of enterococci, which, in turn, exacerbate ethanol-induced liver disease both in mice and humans.

The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an “endocrine organ” with potential to alter host physiology, perhaps to their own favor. We propose the term “sterolbiome” to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.

We have developed a simple and accurate HPLC method for measurement of fecal bile acids using phenacyl derivatives of unconjugated bile acids, and applied it to the measurement of fecal bile acids in cirrhotic patients. The HPLC method has the following steps: 1) lyophilization of the stool sample; 2) reconstitution in buffer and enzymatic deconjugation using cholylglycine hydrolase/sulfatase; 3) incubation with 0.1 N NaOH in 50% isopropanol at 60°C to hydrolyze esterified bile acids; 4) extraction of bile acids from particulate material using 0.1 N NaOH; 5) isolation of deconjugated bile acids by solid phase extraction; 6) formation of phenacyl esters by derivatization using phenacyl bromide; and 7) HPLC separation measuring eluted peaks at 254 nm. The method was validated by showing that results obtained by HPLC agreed with those obtained by LC-MS/MS and GC-MS. We then applied the method to measuring total fecal bile acid (concentration) and bile acid profile in samples from 38 patients with cirrhosis (17 early, 21 advanced) and 10 healthy subjects. Bile acid concentrations were significantly lower in patients with advanced cirrhosis, suggesting impaired bile acid synthesis.

The study examined the associations between religiosity, spirituality, and happiness in 354 outpatients suffering from neurological disorders. After accounting for severity of cognitive decline, physical activity level, depression severity, and demographic variables (i.e., subject age, sex, ethnicity, and marital status) multivariate linear regression revealed a unique association between the Spiritual Well-Being Existential Spirituality scale (SWBS ES), and not the SWBS Religious Scale (SWBS RS), with both the Pemberton Remembered Happiness Index (PHI R) (p < 0.001), and the Pemberton Experienced Happiness Index (PHI E) (p < 0.001). Interventions focused on existential spirituality may improve health related quality of life among adult medical patients with neurological illness.

In the original PDF version of this Article, which was published on 16 October 2017, the publication date was incorrectly given as 10 October 2017. This has now been corrected in the PDF; the HTML version of the paper was correct from the time of publication.