Bowel Movement Frequency Is Not Linked With Cognitive Function in Cirrhosis.

The spectrum of hepatic encephalopathy (HE) ranges from overt HE (OHE) to cognitive impairment (ie, covert) HE (CHE).1 The first-line therapy is lactulose, which is titrated to achieve ~2-3 soft/loose daily bowel movements (BM). This metric is considered dogma for practitioners despite erratic results, GI adverse events, and poor tolerance in Western countries.1 There are logistic barriers for the widespread uptake of rifaximin, the second-line therapy. Moreover, although BM frequency-directed dose titration of lactulose is the usual practice, its impact on objective cognitive performance is unclear. Our aim is to determine the impact of BM frequency on cognition in patients with/without prior OHE.

The Prediction of In-Hospital Mortality in Decompensated Cirrhosis with Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a condition in cirrhosis associated with organ failure (OF) and high short-term mortality. Both the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD) ACLF definitions have been shown to predict ACLF prognosis. The aim of this study was to compare the ability of the EASL-CLIF versus NACSELD systems over baseline clinical and laboratory parameters in the prediction of in-hospital mortality in admitted patients with decompensated cirrhosis. Five NACSELD centers prospectively collected data to calculate EASL-CLIF and NACSELD-ACLF scores for admitted patients with cirrhosis who were followed for the development of OF, hospital course, and survival. Both the number of OFs and the ACLF grade or presence were used to determine the impact of NACSELD versus EASL-CLIF definitions of ACLF above baseline parameters on in-hospital mortality. A total of 1031 patients with decompensated cirrhosis (age, 57 ± 11 years; male, 66%; Child-Pugh-Turcotte score, 10 ± 2; Model for End-Stage Liver Disease [MELD] score, 20 ± 8) were enrolled. Renal failure prevalence (28% versus 9%, P < 0.001) was more common using the EASL-CLIF versus NACSELD definition, but the prevalence rates for brain, circulatory, and respiratory failures were similar. Baseline parameters including age, white cell count on admission, and MELD score reasonably predicted in-hospital mortality (area under the curve, 0.76). The addition of number of OFs according to either system did not improve the predictive power of the baseline parameters for in-hospital mortality, but the presence of NACSELD-ACLF did. However, neither system was better than baseline parameters in the prediction of 30- or 90-day outcomes. The presence of NACSELD-ACLF is equally effective as the EASL-CLIF ACLF grade, and better than baseline parameters in the prediction of in-hospital mortality in patients with cirrhosis, but not superior in the prediction of longer-term 30- or 90-day outcomes.

Focused Education Increases Hepatocellular Cancer Screening in Patients with Cirrhosis Regardless of Functional Health Literacy.

BACKGROUND: Health education interventions are successful in modifying lifestyle. Functional health literacy (FHL) can determine patient adherence to clinic visits and procedures and may adversely impact the success of these interventions. AIMS: We sought to evaluate the hypothesis that a health education intervention would improve compliance with hepatocellular cancer (HCC) screening and that poor FHL would reduce such compliance. METHODS: We assessed FHL using a short version test of functional health literacy in adults (STOFHLA). Cirrhotic patients free of HCC were prospectively enrolled from clinics and provided an educational intervention consisting of focused physician-led discussion regarding cirrhosis and HCC, along with written material on these topics for the subject to review at home. Patients were subsequently followed for 6 months (prospective time period), and the same cohort's clinic/HCC screening behavior between 6 and 12 months prior to the educational intervention (retrospective time period) was compared. RESULTS: In total, 104 cirrhotic patients (age 60.01 ± 8.58 years, 80% men, MELD 12.70 ± 5.76) were included. Of these, 89 (85.57%) of patients had educational level 12th grade and higher. There were 76% (n = 79) with adequate, while 24% (n = 25) had inadequate/marginal FHL on S-TOHFLA. The number of HCC-related imaging increased from 59 (56.7%) to 86 (82.6%, p < 0.0001) post-education in the prospective compared to prior time period which was similar regardless of FHL. CONCLUSIONS: While the educational intervention was successful in improving compliance with HCC screenings, FHL status did not impact the power of this intervention. Hence, the combination of specific verbal information, along with targeted written material, improved compliance with clinic visits and liver imaging for HCC.

Microbiome: Emerging Concepts in Patients with Chronic Liver Disease.

The gut microbiome is an exciting new area of research in chronic liver disease. It has shown promise in expanding our understanding of these complicated disease processes and has opened up new treatment modalities. The aim of this review is to increase understanding of the microbiome and explain the collection and analysis process in the context of liver disease. It also looks at our current understanding of the role of the microbiome in the wide spectrum of chronic liver diseases and how it is being used in current therapies and treatments.

Nutritional Assessment in Inpatients With Cirrhosis Can Be Improved After Training and Is Associated With Lower Readmissions.

Malnutrition is widely prevalent in cirrhosis patients, which can worsen sarcopenia, hepatic encephalopathy (HE), and overall prognosis. We aimed to define the frequency of nutritional assessments of patients with cirrhosis in retrospective and prospective (after educational training) cohorts and to evaluate prospective changes along with their effects on 90-day readmissions. This study was conducted in 2 phases. Retrospectively, records of hospitalized patients with cirrhosis from the university and Veterans Affairs Medical Center (VAMC) settings were reviewed to assess nutritional status, if a nutrition consultation occurred, the number of days patients were nil per os (npo) and received inadequate nutrition, and if nutritional management was guideline directed. In the prospective phase, after dedicated educational efforts directed at the stakeholders regarding nutritional guidelines for patients with cirrhosis, subsequently hospitalized cirrhosis patients had nutritional and 90-day readmission data collected for comparison between groups. In total, 279 patients were included in the retrospective phase (150 university/129 VAMC), and 102 VAMC patients were in the prospective phase. Cirrhosis severity, reason for admission, and hospital course were similar between groups regardless of cohort, ie, prospective versus retrospective or VAMC versus university. The prospective group had significantly more nutritional consultations and assessments (74.5% versus 40.1%; P < 0.001) compared with the retrospective group regardless of comparisons between the VAMC and university cohorts. Both groups had a similar number of days npo, but the prospective group had fewer days of inadequate nutrition. The 90-day readmission rate was significantly lower in the prospective group versus the retrospective group (39.4% versus 28.4%; P = 0.04), which was associated with greater nutrition outpatient follow-up. In conclusion, nutritional consultation rates in inpatients with cirrhosis can be significantly improved after educational intervention and is associated with lower 90-day readmission rates.

Neutrophil-to-Lymphocyte Ratio Associates Independently With Mortality in Hospitalized Patients With Cirrhosis.

BACKGROUND & AIMS: The neutrophil to lymphocyte ratio (NLR) is a biomarker of immune dysregulation in patients with cirrhosis and is inexpensive to measure. We investigated the association between NLR and mortality in hospitalized patients with cirrhosis at 4 liver transplant centers, controlling for severity of acute-on-chronic liver failure (ACLF). METHODS: We performed a retrospective study using data from the North American Consortium for the Study of End-stage Liver Disease on patients with index hospitalizations for cirrhosis from December 2011 through December 2016. We collected data on patient demographics, NLR, model for end-stage liver disease (MELD) scores, serum levels of Na, cirrhosis stages, infections, hepatocellular carcinomas, and ACLF severity (based on number of organ failures). Competing risk regression analysis evaluated mortality within 1 year after hospital discharge, accounting for competing events (liver transplant). RESULTS: At admission, the patients' mean age was 57 years, mean MELD score was 21, and mean serum level of Na was 134 mmol/L. Sixty-eight patients had no organ failure, 21 patients had 1 organ failures, 7 patients had 2 organ failures, 4 patients had 3 organ failures, and 1 patient had 4 organ failures; 36% of the patients had confirmed or suspected infections. In univariate models, risk of death associated with increasing NLR, up to a value of 8 (hazard ratio [HR]= 1.14; 95% CI, 1.07-1.20; P < .001), and NLR quartile (for NLR range of 3-5, HR = 2.17; for NLR range of >5-9, HR=2.46; for NLR quartile >9, HR=2.84 vs the lowest quartile [NLR<3]) (P ≤ .001). The NLR remained statistically significant in multivariable models, adjusting for age, MELD score, hepatocellular carcinoma, and ACLF severity. Additionally, NLR was a statistically significant independent predictor of length of index hospital stay and mortality within 90 days after discharge. CONCLUSION: In a retrospective analysis of patients with cirrhosis, we found NLR to associate with death within 1 year after non-elective hospitalization. In these patients, the risk of death associated with acute immune dysregulation persists long after their initial hospitalization.

Assessment of the spectrum of hepatic encephalopathy: A multicenter study.

Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD.

Integrin-Linked Kinase in Muscle Is Necessary for the Development of Insulin Resistance in Diet-Induced Obese Mice.

Diet-induced muscle insulin resistance is associated with expansion of extracellular matrix (ECM) components, such as collagens, and the expression of collagen-binding integrin, α2ß1. Integrins transduce signals from ECM via their cytoplasmic domains, which bind to intracellular integrin-binding proteins. The integrin-linked kinase (ILK)-PINCH-parvin (IPP) complex interacts with the cytoplasmic domain of ß-integrin subunits and is critical for integrin signaling. In this study we defined the role of ILK, a key component of the IPP complex, in diet-induced muscle insulin resistance. Wild-type (ILK(lox/lox)) and muscle-specific ILK-deficient (ILK(lox/lox)HSAcre) mice were fed chow or a high-fat (HF) diet for 16 weeks. Body weight was not different between ILK(lox/lox) and ILK(lox/lox)HSAcre mice. However, HF-fed ILK(lox/lox)HSAcre mice had improved muscle insulin sensitivity relative to HF-fed ILK(lox/lox) mice, as shown by increased rates of glucose infusion, glucose disappearance, and muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. Improved muscle insulin action in the HF-fed ILK(lox/lox)HSAcre mice was associated with increased insulin-stimulated phosphorylation of Akt and increased muscle capillarization. These results suggest that ILK expression in muscle is a critical component of diet-induced insulin resistance, which possibly acts by impairing insulin signaling and insulin perfusion through capillaries.