Sly Saint
Senior Member (Voting Rights)
Opinion Piece
Abstract
seemed well thought out... until the last bit
open access
https://www.wjgnet.com/1007-9327/full/v25/i28/3669.htm
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.
Measurement
Although there is a proliferation of measurement tools to assess fatigue, there is no instrument that can provide both specificity and sensitivity for measuring fatigue. The lack of a tool is part of the problem that leads to under diagnosis, under recognition, and under treatment of fatigue in CLD patients.
Part of the issue is that the tools that are currently used do not adequately capture the complexity and dimensionality of fatigue[17]. None of the commonly used tools address all aspects of fatigue. Commonly assessed areas include: Descriptions or characterizations of fatigue, feelings of distress associated with fatigue, presumed causes of fatigue and consequences of fatigue[18]. It is important to recognize what components of fatigue are being assessed and what components of fatigue should be assessed.
Because there are no tools that address all of these components, it is important for researchers to consider what it is about fatigue that is relevant to the current research or patient and use that to drive the selection of a specific measure[17]. Please see Table 2 for a summary of instruments.
A significant amount of literature has been written about the treatment of fatigue in MECFS and cancer related fatigue[70-72]. These reviews discuss a variety of non-pharmacological approaches to fatigue management including weight loss, exercise, dietary supplements, acupuncture, insomnia treatment and cognitive and behavioral interventions. These have helped guide treatment for fatigue in CLD.
seemed well thought out... until the last bit
open access
https://www.wjgnet.com/1007-9327/full/v25/i28/3669.htm