Jillian K. Price

Depression in Patients with Nonalcoholic Fatty Liver Disease and Chronic Viral Hepatitis B and C

BACKGROUND Patients with chronic liver disease (CLD) and depression may be at a higher risk for various complications, including impaired quality of life and more advanced liver disease. The purpose of this study was to determine the prevalence of depression in CLD patients (non-alcoholic fatty liver disease (NAFLD), Hepatitis B (HBV), and Hepatitis C (HCV)) and to identify potential clinical and laboratory correlates of depression in these patients. METHODS We used a database of CLD patients that contains extensive clinical (including self-reported depression) and laboratory data for each patient. We compared the prevalence of depression in patients with HBV, HCV, and NAFLD. We also used regression models to find independent predictors of depression in these patients. RESULTS Of 878 CLD patients, 207 (23.6%) had a diagnosis of depression (NAFLD 27.2%, HCV 29.8%, and HBV 3.7%). Examination of predictors of depression differed by the type of chronic liver disease. For NAFLD, independent predictors of depression were the presence of hypertension, smoking, history of lung disease, being female, and non-African-American. For HBV patients, the only independent predictor of depression was excessive alcohol consumption (defined as >10 g/d), while for HCV patients, independent predictors were being female and non-Asian, presence of fatigue, and excessive alcohol intake. CONCLUSIONS This study demonstrates that individuals with NAFLD and HCV have a higher prevalence of depression than HBV patients and the rates of depression reported for the general population. The most consistent correlates of depression status in CLD patients are being female and excessive alcohol consumption.

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.

Comparison of activity level among patients with chronic liver disease

Purpose: To determine whether self-reported maximal and daily activity levels are impaired among patients with nonalcoholic fatty liver disease (NAFLD), hepatitis C (HCV) and hepatitis B (HBV). Methods: Clinicodemographic, diagnostic, self-report and standard laboratory data were obtained. Univariate, multivariate and regression analyses were performed comparing group maximal (Maximum Activity Score [MAS]) and daily activity scores (Adjusted Activity Score [AAS]), adjusted for age and gender. Results: Two hundred twenty-two patients completed activity-level self-reports (mean age [52.4 ± 10.0 years], BMI [28.3 ± 6.58], 31.2% NAFLD, 48.3% HCV, 20.3% HBV). On multivariate analysis, significantly higher MAS (p < 0.05) and AAS in HBV patients correlated with absence of cirrhosis, younger age, male gender (higher MAS) and lower BMI (higher AAS). Lowest activity levels were found primarily in obese patients (p < 0.009). Compared with population norms, NAFLD and HCV cohorts scored mildly disabled on MAS; the HBV cohort scored low normal. Mild disability on AAS was observed in patients with HBV; moderate disability in those with NAFLD, HCV. Conclusions: All groups had significantly lower activity levels than population norms. Nonobese patients showed significantly less disability than obese patients. Patients with NAFLD and HCV are likely to have lower levels than those with HBV without cirrhosis. This presents an additional risk factor for disability and mortality. Implications for Rehabilitation Hepatitis B (HBV), hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD) patients had significantly lower activity levels than expected for their age and gender, as measured by the Human Activity Profile (HAP). Overweight and normal weight chronic liver disease (CLD) patients showed significantly less disability than obese chronic liver disease patients. Patients with NAFLD and HCV are likely to participate in low levels of activity that require fewer metabolic equivalents for completion, adding an additional risk factor for disability and mortality. Targeting low activity level in CLD patients, and decreasing BMI below the obesity threshold, may reduce disability and risk of mortality.

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.

Measures of Function and Health-related Quality of Life

Introduction to Function and Health-Related Quality of Life (HRQL) Measures 321 Definitions 3 21 Reasons for Measuring Function and HRQL 3 21 What do Function and HRQL Measure? 3 22 How are Function, QOL, and HRQL Measures Used? 323 Examples of Functional Measures and Health-Related Quality of Life Measures 324 Functional Measures 3 24 HRQL and QoL Measures 3 24 Criteria for Selection of HRQL Measures 3 26 Specific Functional Measures, HRQL, and QoL Instruments 3 27 Other Instruments to Consider 328 Importance of Quality of Life Measures for Health Care 328 Summary Questions 329 References 329

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.

Longitudinal Study of Dietary Habits and Activity Level in Patients With Chronic Liver Disease (CLD)

(TFEQ), food intake (Food Frequency Questionnaire-FFQ) and mindfulness (Five Facet Mindfulness Questionnaire-FFMQ). Mean TFEQ scores, as well as calories, fat and sugar intake were compared before and after MBSR using paired t-tests. Scatterplots and correlation analyses examined the association between mindfulness score, TFEQ score and food intake. Changes from baseline to post-MBSR were used to calculate effect size (Cohens d). Results: Over the course of the study, the mean FFMQ score increased significantly (baseline: 105.2 ± 20.8; post-MBSR: 122.1 ± 23.7, p < 0.05). A significant negative correlation was found between change in mean mindfulness score and change in EE score (r = -0.435, p<.05). A significant decrease in depression score was significantly associated with increase in FFMQ score (-0.533, p < 0.01) and decrease in EE, UE scores (EE: 0.401, p= 0.047; UE: 0.442, p=0.027). Mean scores for cognitive restraint, UE and EE did not change significantly from preto post MBSR. Effect size was moderate for cognitive restraint (.42); and negligible for uncontrolled eating (0.03) and emotional eating (0.012). Mean intake of calories, total fat, fruits and vegetables were not significantly different after MBSR as compared to baseline. Conclusions: These results suggest that despite a significant increase in general mindfulness skills, participation in MBSR did not produce a clinically significant effect on eating behaviors or food intake. However, the significant correlation between an increase in mindfulness and change in EE suggests that mindfulness training may play a role in changing eating behaviors.

Chapter 21 – Measures of Function and Health-Related Quality of Life

Abstract National and international health agencies define health as physical, mental, and social well-being of an individual. Measurement of these domains poses a challenge to clinicians and researchers because administering tests is time consuming, and the information obtained include self-reports. Nonetheless, these measures of function, quality, and health-related quality of life (HRQL) are important to patients and are critical for quality care. Function is the usual or customary activities of a person. Functional status is the degree to which an individual can perform chosen roles without limitation in three key domains: physical, social, and psychocognitive. HRQL measurements assess a patients perception of his/her ability to perform function as influenced by illness. General quality of life (QoL) is a reflection of overall satisfaction with life. This chapter discusses an approach to the selection and application of measures, using patient-reported outcomes that are designed to evaluate function, HRQL and QoL; and identifies valid, reliable, and sensitive instruments that have been used in clinical research. It presents the new techniques, item response theory, and computer adaptive testing, used in creating efficient and appropriate self-reports.

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.

Association of Serum Biomarkers With Fatigue in Patients With Chronic Liver Disease

Background and Aims: Fatigue is a common symptom of chronic liver diseases (CLD), including non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CH-C). The mechanisms or correlates of fatigue in these patients have not been well studied. We aimed to determine if there is a correlation between self-reports of physical activity associated fatigue (peripheral fatigue) or more global lack of energy and motivation (central fatigue); with serum markers of inflammation, or with abnormalities of glucose and lipid metabolism. Methods: 31 untreated patients (age 52.5 ±6.8 years, 66.7% male, BMI 32.4 ± 5.5, 26.7% DM, 0% cirrhosis) with CLD (biopsy proven NAFLD or CH-C with viremia) participated in the study. Fasting blood samples were obtained and were assessed for levels of cytokines (IL-6, IL-8, and TNF-α), serotonin, C-peptide insulin, liver enzymes (AST, ALT), glucose, and lipids (triglycerides, total cholesterol, HDL, LDL, and the non-HDL fraction). Cytokines, serotonin, and C-peptide insulin were measured by ELISA following the manufacturers protocols. The remaining parameters were measured by the Cholestech LDX system. Selfreports included standardized and valid measures of depression (short form of CES-D), vitality/energy (vitality subscale of the SF36) and level of activity (Human Activity Profile). Patients were then divided into tertiles by MET value. The middle third was omitted from further analysis; the remaining top third (those with MET >8.8, representing strenuous activity) and bottom third (those with MET 7 and a transformed vitality index score <45. Only patients meeting these criteria were defined as having central fatigue. Groupwise comparisons were made by Mann-Whitney test, and correlations were assessed by Spearman Rho. Results: In comparison to CLD patients without peripheral fatigue, CLD patients who had peripheral fatigue (n=23) had significantly elevated serum levels of IL-6 (7.2±13.5 pg/mL vs. 1.6±0.74 pg/mL, p<0.01) and IL-8 (22.8±11.2 vs. 15.7±6.8 pg/mL, p<0.05); respectively. In terms of central fatigue, the ratio of AST/ALT was significantly lower in CLD patients with central fatigue than those CLD patients without central fatigue (0.862±0.166 vs. 1.118±0.283, p= 0.004). Conclusions: The current study demonstrates that a substantial majority of patients with CLD report significant peripheral fatigue. This type of fatigue is linked to elevated serum levels of IL-6 and IL-8, implying an inflammatory component present in patients with peripheral fatigue but not in those with central fatigue. Further study into the nature and extent of fatigue associated with CLD is warranted.