Carey Escheik

Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study.

High intensity exercise improves metabolic status and may potentially mobilise hepatic fat.

Quality of Life in Cirrhosis

Quality of life is a construct that reflects the positive and negative aspects of one’s life, and is expanded upon by health-related quality of life (HRQL), which specifically address the impact of health on patients’ well-being. Cirrhosis is the culmination of various pathways that leads into development of advanced hepatic fibrosis with its complications. This paper addresses the impact of cirrhosis on individuals HRQL. In addition, we will define what disease specific and general HRQL instruments aim to measure. We discuss the liver disease specific scales [Chronic Liver Disease Questionnaire (CLDQ), Liver Disease Quality of Life 1.0 (LDQOL)] and the most commonly used generic health profile [Short Form 36 Profile (SF-36)]. Furthermore, we examine recent literature which describes how to measure and what is known about quality of life of patients with cirrhosis. This information gives insight to health care providers concerning the impact of disease on patients if treatments are not only to improve health but also function and unexpected treatment outcomes.

Effects of Viral Eradication With Ledipasvir and Sofosbuvir, With or Without Ribavirin, on Measures of Fatigue in Patients With Chronic Hepatitis C Virus Infection.

BACKGROUND & AIMS Fatigue is a disturbing symptom of chronic hepatitis C virus (HCV) infection. We assessed the effects of sustained virologic response 12 weeks after the end of therapy (SVR12) on fatigue. METHODS We performed a retrospective analysis of 100 patients with chronic HCV infection who achieved an SVR12 after treatment with ledipasvir and sofosbuvir, with or without ribavirin. Data were collected on fatigue-related patient-reported outcomes (PROs) and assessed by using the Functional Assessment of Cancer Therapy-Fatigue scoring system and the Vitality subscale of Short Form 36. We measured levels of cytokines and growth factors in frozen serum samples collected at baseline, week 12 of treatment, and 4 weeks after treatment. Central fatigue and peripheral or muscle fatigue (PF) were determined by using items from PROs. Serum levels of cytokines, growth factors, serotonin, alanine aminotransferase, and aspartate aminotransferase were measured by using the Bio-Plex, enzyme-linked immunosorbent, and enzymatic assays. RESULTS Compared with baseline, 4 weeks after the end of treatment, all fatigue-associated PROs improved significantly. Baseline PROs correlated inversely with serum level of interferon-γ; level of platelet-derived growth factor correlated with PF, central fatigue, and total fatigue score. Only PF correlated with serum level of serotonin. At baseline, high PF scores correlated with high serum levels of serotonin and low levels of interleukin-10 and tumor necrosis factor-α. In multivariate analysis, serum level of interleukin-8 was associated with greater fatigue (P < .02). Reductions in levels of chemokine (C-C motif) ligand 2 (also called monocyte chemotactic protein 1) were associated with fatigue after treatment (P = .0165). CONCLUSIONS In an analysis of data from patients with chronic HCV infection participating in a clinical trial of ledipasvir and sofosbuvir, SVR12 was associated with reduced fatigue, compared with baseline. High baseline serum levels of interferon-γ were associated with fatigue. Reductions in levels of chemokine (C-C motif) ligand 2 were associated with persistent fatigue after SVR12. Central and peripheral fatigue each associated with different biomarkers, suggesting different pathogenic pathways.

Multiple factors predict physical performance in people with chronic liver disease.

ObjectiveThe aim of this study was to assess whether physical performance correlates with metabolic and inflammatory measures in research subjects with chronic liver disease. DesignThis is a prospective, descriptive cohort study correlating performance on a 6-min walk test with cardiorespiratory variables, metabolic measures (glucose [GLU], C-peptide insulin, and lipids), liver enzymes (aspartate aminotransferase and alanine aminotransferase), and the proinflammatory cytokine interleukin-8 (IL-8). ResultsThis study enrolled 51 subjects (18 women) with chronic liver disease: 41% (n = 21) with nonalcoholic fatty liver disease and 59% (n = 30) with hepatitis C virus. Age, resting heart rate, and fasting GLU correlated significantly with distance walked (P’s < 0.05). First quartile “poor performers” (n = 14) and fourth quartile “high performers” (n = 14) showed differences in age, sex, fasting GLU, and IL-8 level (P’s < 0.05). Combining the number of abnormal serum values (IL-8, C-peptide insulin, GLU, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, triglyceride, and total cholesterol) did not correlate with distance walked (P > 0.90). However, in multiple regression analysis, a model that included sex, age, resting heart rate, IL-8 level, and fasting GLU level explained approximately 39% of the variance in the distance walked during the test. ConclusionsOlder age, female sex, abnormal levels of the proinflammatory cytokine IL-8, abnormalities of GLU metabolism, and high resting heart rate are associated with poor physical performance in subjects with chronic liver disease. Poor physical performance is associated with physiologic, metabolic, and inflammatory abnormalities in subjects with nonalcoholic fatty liver disease and hepatitis C virus.

Perception of Effort During Activity in Patients With Chronic Hepatitis C and Nonalcoholic Fatty Liver Disease

Ratings of perceived exertion (RPE) are used to monitor and prescribe exercise intensity for a variety of patient populations. It is important to understand RPE in different patient populations to ensure appropriate prescriptions and maximize the likelihood of adherence. Chronic liver diseases (CLDs) are a constellation of diseases that are associated frequently with fatigue, metabolic abnormalities, and cardiovascular disease, all targets for prescription of exercise. However, there have been no investigations of the correlates of RPE in those with CLD.

Demonstration of two types of fatigue in subjects with chronic liver disease using factor analysis

PurposeThe purpose of this investigation was to determine if it was possible to separate fatigue self-reports into two distinct types of fatigue symptom clusters in research subjects with chronic liver disease (CLD). It was hypothesized that when items from the Medical Outcomes Study Short-Form (SF-36v2) are combined with items from the Fatigue Severity Scale (FSS), these distinct factors will emerge.MethodsConfirmatory and exploratory factor analyses from data collected in a prospective, natural history study of CLD patients were conducted. Items were selected from the SF-36v2 and the FSS for entry into the factor analyses. In order to establish convergent and discriminant validity, derived factor scores were correlated with subscale scores of the Human Activity Profile (HAP), Mental Component Score (MCS) from the SF-36v2, and the Emotional Functioning Subscale of the Chronic Liver Disease Questionnaire (CLDQ-EF).Results106 participants with CLD were included (50% female; age: 51 ± 10). Two factors were identified. The factors included one that clustered around questions addressing fatigue related to physical activity (peripheral fatigue) and the other to the questions addressing generalized fatigue that did not require physical tasks to produce the fatigue (central fatigue). The standardized factor loadings of all items were greater than 0.6 on their underlying constructs. Moreover, all factor loadings are significant at p < 0.01. Peripheral fatigue was related to HAP (r = 0.26, r = 0.24, p < 0.01), as was central fatigue (r = −0.34, r = −0.33, p < 0.01). Central fatigue was related to MCS and CLDQ-EF (r = −0.60; r = −0.63, p < 0.01), whereas peripheral fatigue was not (r = 0.07, p > 0.40). We then tested the original scales to determine if the newly created factors correlated better with the validity measures. The full FSS did not correlate as well as the newly created central fatigue scale, while the original peripheral fatigue scale (the SF-36v2 physical functioning) was more related to HAP than the newly created scale.ConclusionsIn individuals with CLD, two separate factors pertaining to fatigue were identified. This recognition of the multifaceted nature of fatigue may help increase the specificity of self-reports of fatigue and lead to treatments that can specifically address the underlying factors contributing to fatigue.

Sa1000 Medications Affecting the Autonomic Nervous System (ANS) Do Not Explain Abnormal Diastolic Blood Pressure in Patients With Chronic Hepatitis C (Ch-C) or Non-Alcoholic Fatty Liver Disease (NAFLD)

Background: Previous work has shown that high resting diastolic blood pressure in patients with liver disease is associated with low levels of physical performance. Anti-hypertensive medications and some other commonly prescribed anti-depression medications can influence the ANS and, in part, may be able to explain these findings. Aim: The purpose of this analysis was to determine whether medication influencing ANS activity such as beta-2 adrenergic agonists may be significantly associated with abnormal diastolic blood pressure in patients with CH-C and NAFLD. Methods: 47 subjects (62% male, 45% NAFLD, 55% HCV, age 50.5 ± 9.0, BMI 31.5 ± 5.8, 59% obese; 37% diagnosed hypertension, 35% hyperlipidemia, 24% diabetes mellitus, 22% metabolic syndrome, AST 50.2 ± 36.5, ALT 58.0 ± 39.0) were enrolled. Current medications of CH-C and NAFLD patients were categorized by mechanism of action and indication along with clinico-demographic information. Pearsons correlation and regression of diastolic blood pressure was run. Results: 27.3% of patients had elevated diastolic blood pressure at baseline. Of these patients, 17.6% were not taking antihypertensive medications, 76.5% were not taking any medications to increase ANS activity. As expected, the use of anti-hypertension medications were diffierent between those diagnosed with hypertension and those without hypertension (p=0.0001). On the other hand, the prevalence of beta-2 adrenergic agonists was not significantly different between the two groups(p=.642). Pearsons correlation showed no significant correlations between diastolic blood pressure and any medication indication. No correlation existed between diastolic blood pressure and either beta-2 adrenergic agonists (r=0.083) or medications with known ANS effects (r=0.071). The medication model of diastolic blood pressure (All current medications = GERD/digestion + depression/sleep + antihypertensive + GABA/anxiety + diabetes + allergy/asthma/pulmonary + hyperlipidemia/hypercholesterolemia + beta2 adrenergic agonists + supplements/other) did not show any correlation (r= 0.266, p=0.427). Conclusions: The presence of beta-2 adrenergic agonists and medications with ANS activity does not significantly impact diastolic pressure in patients with chronic liver diseases. In these patients, the majority of diastolic blood pressure variance cannot be explained by medication. This data suggest that diastolic blood pressure abnormality in chronic liver disease is related to other currently unknown reasons.

Su1034 Central Fatigue and Peripheral Fatigue in Patients With Chronic Hepatitis C and Their Relationships to Patient-Reported Outcomes

A S L D A b st ra ct s only compared to patients with DM/HCV (HR 1.041, 0.92-1.16). There was also no significant difference in survival between patients with DM only and those with DM/HCV in each HgA1C categories ( 8%). Conclusions: Blood glucose control does not offer a survival advantage in veterans with HCV and DM. These data are consistent with published clinical trials of lack of survival benefit with tight glucose control and even increased mortality such as in the ACCORD study. Demographics

Tu1065 Validation of Borg Self-Reported Activity and Exertion With Physical Performance Measures in Subjects With Chronic Liver Disease (CLD)

NF-κB activation) and increase in p-MLC (reflective of loss of tight junction integrity) expression was noted with TPN, and these downstream factors were sustained with ETC treatment. As both could affect EBF, this was then me measured with TER, permeability of FITC-dextran and junctional protein staining. EBF which declined with TPN, was partially restored with ETC. Interestingly, TPN led to a decline in many ErbB ligands (EGF, HBEGF, amphiregulin and neuregulins) and there were also partially prevented with ETC. Conclusions: TNF-α played an important role in TPN-associated intestinal atrophy and intestinal barrier dysfunction. Anti-TNF treatment protected these changes potentially by sustaining p-Akt and ErbB signaling, and inhibiting NF-κB signaling.