Importance of fatigue and its measurement in chronic liver disease

The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. Metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. Many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have been used singly or in combination and include: physical performance measures, cognitive performance measures, mood/behavioral measures, brain imaging and serological measures. Treatment with non-pharmacological agents have been shown to be effective in symptom reduction, whereas pharmacological agents have not been shown effective.

Interrelationship between physical activity and depression in nonalcoholic fatty liver disease

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is associated with a sedentary lifestyle and depressive symptoms.It is also well established that physical inactivity and depressive symptoms are related.However,an investigation of the interaction between all of these factors in NAFLD has not been previously conducted.AIM To investigate the interrelationship between physical inactivity and depressive symptoms in individuals with NAFLD.METHODS Data from the Rancho Bernardo Study of Healthy Aging were utilized.589 individuals were included in the analyses(43.1%male;95.8%non-Hispanic white;aged 60.0±7.0 years).NAFLD was defined by using the hepatic steatosis index,depression using the Beck Depression Inventory,and physical activity by selfreport of number of times per week of strenuous activity.Multivariable generalized linear regression models with Gamma distribution were performed to investigate the proposed relationship.RESULTS About 40%of the sample had evidence of NAFLD,9.3%had evidence of depression,and 29%were physically inactive.Individuals with NAFLD and depression were more likely to be physically inactive(60.7%)compared to individuals with neither NAFLD nor depression(22.9%),individuals with depression without NAFLD(37.0%),and individuals with NAFLD without depression(33.3%).After accounting for various comorbidities(i.e.,age,sex,diabetes,hypertension,obesity),individuals with NAFLD and higher levels of physical activity were at a decreased odds of having depressive symptoms[16.1%reduction(95%confidence interval:-25.6 to-5.4%),P=0.004],which was not observed in those without NAFLD.CONCLUSION Individuals with NAFLD have high levels of physical inactivity,particularly those with depressive symptoms.Because this group is at high risk for poor outcomes,practitioners should screen for the coexistence of depressive symptoms and NAFLD.This group should receive appropriate interventions aimed at increasing both participation and levels of intensity of physical activity.