Importance of fatigue and its measurement in chronic liver disease

Abstract

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.

Patient‐reported outcomes in patients with non‐alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire‐non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis

“…In the previous studies conducted in the USA, almost all domains are reported to be impaired except for abdominal symptoms and worry domains in patients with NAFLD, 20,34,35 and fatigue domain is the most impacted 34,36 . Thus, NAFLD is thought to be a symptomatic disease 20,34–36 . However, there were no available data for CLDQ‐NAFLD in Japanese patients.…”

“…In patients with chronic liver disease, 50.0%–80.0% of patients are reported to have fatigue 36 . Fatigue domain is the most impacted domain in CLDQ‐NAFLD/NASH 20 .…”

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

“…Moreover, in the assessment of patients, it is important to acknowledge that NAFLD is also associated with a range of nonspecific physical and mental symptoms that can indirectly influence cognitive function [ 18 , 19 ]. Specifically, fatigue, that is a common complaint among patients with NAFLD and other liver diseases, can affect attention, concentration, and working memory [ 19 , 150 , 151 , 152 ]. In addition, NAFLD patients more frequently suffer from neuropsychiatric symptoms such as anxiety and depression that are also associated with impaired memory, attention, and executive function [ 153 , 154 , 155 ].…”

Importance of Monitoring Physical Function for Quality of Life Assessments in Hematopoietic Stem Cell Transplantation Patients: A Prospective Cohort Study

“…We did not find any association between laboratory findings and physical function in the present cohort. Usually liver or kidney function may be related with fatigue, weakness, and decreased activity (21,22). Considering no relationship between organ and physical function in acute period after HSCT, decreased physical function may be originated from immobilization (23).…”