• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Cholestasis could it be a factor in ME/CFS?

Emootje

Senior Member
Messages
356
Location
The Netherlands
Cholestasis is a pathologic state of reduced bile flow from the liver into the gut.
It is characterized by an accumulation of bile acids in the liver and in the blood.
Hydrophobic bile acids are pro-oxidants causing cell damage.

The similarities between cholestasis findings and ME/CFS findings:

Dia1.JPG

Diagnosis of cholestasis:
Elevations of serum bile acid levels

Therapy cholestasis:
Ursodeoxycholic acid
Soluble fiber
Lecithin
Lipoic acid
Vitamin E
SAM-e
NAC

Could ME/CFS be a mild cholestasis?

Systemic hypotension and renal failure in obstructive jaundice-mechanistic and therapeutic aspects
http://jasn.asnjournals.org/content/5/11/1853.full.pdf

Increased plasma levels of atrial natriuretic peptide and endocrine markers of volume depletion in patients with obstructive jaundice.
http://www.ncbi.nlm.nih.gov/pubmed/9462378
 

Emootje

Senior Member
Messages
356
Location
The Netherlands
Inhibition of interferon-?-induced signaling by hyperosmolarity and hydrophobic bile acids

Apart from viral conditions, host factors such as elevated bile acid concentrations are determinants of successful interferon-? (IFN-?) treatment in patients with chronic hepatitis C or B. The present study demonstrates that hydrophobic bile acids inhibit Jak1- and Tyk2-phosphorylation, which lead to blockade of STAT1-mediated IFN-?-signaling in the sodium-taurocholate cotransporting peptide (NTCP)-transfected human hepatoma cell line HepG2, resulting in a decreased mRNA and protein expression of IFN-stimulated genes such as myxovirus resistance protein A (MxA) or dsRNA-activated protein kinase (PKR). In addition, hyperosmotic stress leads to an inhibition of IFN-?-induced Jak1- and Tyk2-phosphorylation, and STAT1/STAT2-phosphorylation and gene expression. This inhibitory effect of hydrophobic bile acids or hyperosmolarity is not due to caspase-mediated cleavage or lysosomal degradation of the cognate receptors or to the generation of oxidative stress, activation of p38- or Erk-mediated MAPK pathways or phosphatase activity. Preincubation with the organic osmolyte betaine blocked the inhibitory effect of bile acids or hyperosmolarity on MxA protein expression, but had no effect on transcript levels or activation of STAT1, suggesting that betaine mediates its effects on MxA expression at a translational or post-translational level. Our findings could provide a rationale for betaine use in cholestatic HBV/HCV patients undergoing interferon therapy.

http://www.ncbi.nlm.nih.gov/pubmed/21028968

CFS patients are associated with STAT1 deficiency.
If STAT1 is disabled or otherwise inactive in the cells of the immune system, treatment with interferon or interferon inducer will not be effective in promoting and establishing the interferon-inducible antiviral and antiproliferative pathways.
http://www.ncf-net.org/forum/P1-STAT1.htm
 

Enid

Senior Member
Messages
3,309
Location
UK
Thanks Emootje - this was very much part of my many symptoms (jaundice like/pale stools). It is good to see these findings coming in now.
 

Emootje

Senior Member
Messages
356
Location
The Netherlands
Thanks Emootje - this was very much part of my many symptoms (jaundice like/pale stools). It is good to see these findings coming in now.
Interesting!
Did you have the serum bile acid test? I am very curious if PWC have increased levels of bile acids in their serum. These things are very toxic in the blood....
 

Enid

Senior Member
Messages
3,309
Location
UK
No such luck here Emootje for bile acid tests - my many ME symptoms (fluctuating and Neurologist concentrating on obvious neurological problems - MRIs etc meant only basic blood and spinal fluid testing). The whole pattern of symptoms seemed to confuse my GP so I excluded the jaundice like symptoms to allow concentration on the worst whilst mostly bedridden including passings out. Not too aware of what was going on at the time.
 

Emootje

Senior Member
Messages
356
Location
The Netherlands
Still a bit confused...can you tell more?
Did they diagnosed you with obstructive jaundice?
And if so, did you received any treatment?
And if so, which symptoms improved after treatment?
 

Enid

Senior Member
Messages
3,309
Location
UK
I'm afraid I can't really help you on that one Emootje - jaundice symptoms - pale stools yellowish pallor etc not investigated as I was passed between the strictly neurological or gynae or bowel specialists (as happens here) and jaundice like symptoms waxed and waned. Presumably viral (blood) tests revealed nothing and that particular matter was never solved.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
A UK NHS Consultant I saw recently said that "Gilbert's Disease" was common in his patients and their families. Not sure if related to this discussion but thought I should mention it as bile related.
 

Emootje

Senior Member
Messages
356
Location
The Netherlands
Only bilirubin is eleveted in Gilbert's Disease. The bile acids in the serum and the gut are normal.
The hyperbilirubinemia plays no role in the etiology of low blood volume, depressed cellular immunity, impaired cardiac performance and endotoxemia in obstructive jaundice.
Increased bile acids in the serum are the main factors.
serum ba.JPG
 

dannybex

Senior Member
Messages
3,555
Location
Seattle
I found this story quite compelling...

Check out this nurses story -- in her case, and others, gallbladder and liver function, and how if they're not functioning well can over a long period of time, result in CFIDS:

http://curezone.com/forums/am.asp?i=1136029

Don't be put off by the term "Chronic Fatigue" in the title. If you read the entire article, she went on to develop CFS, or as it was called for awhile, CFIDS.

d.