RE: : Re: Fatigue

[Guest guest]

Hi ,So apparently someone can develop chronic fatigue syndrome if they have PSC due to a buildup of endotoxins (and this occurs in the biliary epithelial cells). So do you think that if a person who has CFS due to PSC gets a new liver, will the new liver "cure" the PSC AND the CFS??? Or would the person probably still have the CFS even with a new liver.I know I've grossly simplified what you said, but hopefully you can understand my question.Marie

To: From: rhodesdavid1@...Date: Tue, 31 Mar 2009 02:59:33 +0000Subject: Re: Fatigue

Dear Theresa;

I don't think that there is any relationship between fatigue and cirrhosis. For example, one of the world experts on PSC concluded that fatigue in PSC is unrelated to the stage of liver disease:

"Fatigue in patients with PSC is related to depression but not to the severity of the liver disease"

Bjornsson E, Simren M, Olsson R, Chapman RW (2004) Fatigue in patients with primary sclerosing cholangitis. Scand. J. Gastroenterol. 39: 961-968.

http://www.ncbi.nlm.nih.gov/pubmed/15513335

However, there is still controversy about whether fatigue is related to depression in PSC, and this paper says this isn't:

"The prevalence of a depressive disorder in patients with PBC and PSC is not higher than in the general population. Fatigue in patients with PBC and PSC cannot be explained by depression."

van Os E, van den Broek WW, Mulder PG, ter Borg PC, Bruijn JA, van Buuren HR (2007) Depression in patients with primary biliary cirrhosis and primary sclerosing cholangitis. J. Hepatol. 46: 1099-1103.

http://www.ncbi.nlm.nih.gov/pubmed/17399846

My own thoughts on fatigue in PSC are as follows:

1. PSC patients have a higher concentration of the toxic bacterial product lipopolysaccharide (LPS) [also called endotoxin] in their livers (and probably therefore also in their circulation):

Sasatomi K, Noguchi K, Sakisaka S, Sata M, Tanikawa K (1998) Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis.

J. Hepatol. 29: 409-416.

http://www.ncbi.nlm.nih.gov/pubmed/9764987

2. Lipopolysaccharide/endotoxin is now implicated in chronic fatigue syndrome:

Maes M, Mihaylova I, Leunis JC (2007) Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J. Affect. Disord. 99: 237-240.

http://www.ncbi.nlm.nih.gov/pubmed/17007934

3. One of the main mechanisms for neutralizing lipopolysaccharide/endotoxin is by the protein called bacterial-permeability increasing protein (BPI). Patients with IBD and PSC often have antibodies to this protein, probably impairing its ability to neutralize endotoxin.

Stoffel MP, Csernok E, Herzberg C, T, Carroll SF, Gross WL (1996) Anti-neutrophil cytoplasmic antibodies (ANCA) directed against bactericidal/permeability increasing protein (BPI): a new seromarker for inflammatory bowel disease and associated disorders. Clin. Exp. Immunol. 104: 54-59.

http://www.ncbi.nlm.nih.gov/pubmed/8603534

Schultz H (2007) From infection to autoimmunity: a new model for induction of ANCA against the bactericidal/permeability increasing protein (BPI). Autoimmun. Rev. 6: 223-227.

http://www.ncbi.nlm.nih.gov/pubmed/17317612

Schultz H, Weiss J, Carroll SF, Gross WL (2001) The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies. J. Leukoc. Biol. 69: 505-512.

http://www.ncbi.nlm.nih.gov/pubmed/11310835

High serum levels of endotoxin, due to inability to detoxify/neutralize it [because of antibodies against BPI], could potentially contribute to chronic fatigue IF you agree with the afore mentioned paper by Maes et al (2007).

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Does everyone with PSC who experiences fatigue also have cirhossis of the liver? I have been trying to understand the issue of fatigue and I had an extremely disconcerting discussion with a doctor today. I am hoping some of you may be able to help me put my mind at ease.

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