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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.

Thanks

Theresa

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I have fatigue and my last biopsy showed that I'm in stage 2 of PSC (the biopsy was in 11/06). My hepatologist thinks the fatigue is from chronic fatigue syndrome. I think it's from the UC/J-pouch, PSC & AIH & adrenal gland insufficiency & chronic pouchitis.Marie

To: From: alexsmiracle13@...Date: Tue, 31 Mar 2009 00:20:08 +0000Subject: Fatigue

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.

Thanks

Theresa

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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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Share on other sites

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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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