Importance of fatigue and its measurement in chronic liver disease - Gerber et al Jul 28 2019

[Sly Saint]

Opinion Piece

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

 

[Mithriel]

"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). "

That is interesting to know how they are thinking. It is another one of those things where they decide what we are thinking without ever asking. My self motivation has always been fine, it's just that I end up lying on the floor if I don't stop what I am doing. (A common occurrence when I had to do this for the kids)

 

[rvallee]

Central fatigue is characterized by a lack of self-motivation

As far as I'm aware, lack of self-motivation is characterized by lack of self-motivation and fatigue is characterized by fatigue. Those words already have a standard meaning. This is a definition that fundamentally differs from what is commonly understood by fatigue. Of course this redefinition is rather common but, still, words matter. I'm not sure it's worth reading further than that when the central topic being discussed is arbitrarily redefined.

The "central" part seems to try and do a lot of work, whatever is meant by that (likely CSS). Central heating does not suddenly about noise, plumbing or some entirely different definition of the word heating. Doublespeak has no place in medical research. Just say what you mean, deceit is dishonorable and unethical.

 

[mat]

Unlike cancer and myalgic encephalomyelitis/chronic fatigue syndrome (MECFS), there are no specific criteria for a “liver related fatigue” syndrome.

Just because some criteria exist for the first, this doesn't make it an exclusionary disease. I guess I'll never understand why there isn't a universal approach on fatigue and how to approach all potential co-diagnoses. This is how some people with non-viral liver and kidney diseases might end up in (post-viral) CFS studies and cause even greater bias and confusion. Is there any CFS patient who has been diagnosed for all potential co-diagnoses? I doubt it. The costs for this would be in the five digits and there are still doctors who consider it unethical to do biopsies given a manageable condition such as chronic fatigue.

Central fatigue, is mediated by the central nervous system and is characterized by a failure to transmit motor impulses or perform voluntary activities[39], or the inability or reduced ability to perform attentional tasks. Peripheral fatigue, in comparison is a reduction in the ability to exert muscular force after exercise[40] and maintain a maximal force because of muscular limitations[8]. This implies that the source of the fatigue is independent of the muscular apparatus and originates above the neuromuscular junction[41].

This basically is one common explanation for why MG and CFS can not be the same. MG is peripheral while CFS is central. However, MG isn't always manifested completely peripheral. Smooth muscle tone is also involved sometimes, brain fog as well. Both can be attributed to ACh receptors.

CFS, on the other end, not always involves cognitive limitations and lack of motivation. What does remain in their definition, then? The failure to transmit motor impulses, which again is neuromuscular and could be attributed to MG as well. This doesn't mean that I believe that CFS is primarily neuromuscular. But I think CFS can manifest itself also peripheral, especially when cognition is fine but muscles are affected, in all possible regions of the human organism. Maybe it is immunologically mediated, maybe by impaired glycolysis, maybe both.

 

[Snow Leopard]

"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). "

That is interesting to know how they are thinking.

Yes, it shows they do not understand "central fatigue" at all.

The objective fatigue (as measured using electromyography) suffered by patients with muscular dystrophies and peripheral neuropathies is also "central fatigue".

 

[NelliePledge]

Not the first time the terminology is twisted to have surreptitious psychosomatic interpretation