Re:Best practise for PSC management?

[Guest guest]

Here in the UK PSC-Support group we're planning in future to visit out 7 liver units - where the full-range of liver services are availlable, including tx. We have only 7 but the pop. here is 60m. With 300m in the US I wonder how many liver units there are? We want to raise our profile, become better known and increase our membership; For a long time it's obstinately remained at around 400. In addition to that we're also keen to establish what is the best practise for treatment of PSC and we want to see whether our members are getting proper treatment. We know that many are not; especially those who are being treated in general hospitals by gastros who may have no training in hepatology. We've found cases where some of them are learning about PSC from the Internet! Some consultants are refusing to prescribe Urso.

So I'd like to intiate a discussion on what we would consider best practise. Because the cause and progression of PSC remain unclear it's not easy to have a completely logical approach to management and there is no protocol for PSC. I understand that this isn't a simple matter because once a protocol is established you expect to be treated according to that protocol. If you're not the hospital may have a legal problem on its hands. Treatment will depend, in part, on the stage of PSC. If you have cirrhosis you would expect them to look for ascites and monitor the development of varices more carefully. Obviously management will also depend on the presentation of symptoms.

There was some discussion on this last week on the monitoring of progression. I don't think many heps are interested in monitoring this with ERCP or MRCP. They can't do anything about the progression except prescribe Urso, and, as we know - still no evidence that Urso slows progression. There seems to be a general view that ERCP should only be used for diagnosis and therapeutic action. In view of the fact that 5%? of patients are liable to get cholangitis or pancreatitis. Obviously each of us probably wants to know how far our disease has progressed. In my case I requested a biopsy and they said no - it isn't a part of treatment. But I pushed for it. I did find that my PSC had progressed from Stage 3 (pre-cirrhotic) in 1991 to stage 4 cirrhotic.

BEST PRACTISE?

COLONOSCOPY; Annually for those with PSC + IBD. Removal of any polyps and taking of biopsies from the colon.

LFTs Every 6 months?? Other blood tests. FULL BLOOD COUNT (Annually?)

TUMOR MARKERS: CA 19-9, Alpha-Feto Protein or CEA. Annually? ERCP with brushings??

ULTRASOUND: Annually?? 6-monthly for those with cirrhosis. Looking at spleen, liver, intrahepatic portal flow, duct dilatation etc.

BIOCHEMISTRY (BONE PROFILE): + DEXA scan evry 2 years??

EGD (upper abdominal endoscopy) Looking at varices, especially if you have cirrhosis. This can be done at the same time as colonoscopy.

INR. Annually?

VITAMIN DEFFICIENCY (A, D, E, and K.) incl. B12/Follate/Ferritin. blood tests.

Anything else which should be included??????????

At my recent liver outpatient appointment a young and enthusiastic doctor also ordered tests for Auto Antibodies and the 3 tumor markers (overkill??). In addition he wanted me to have an ERCP but the consultant stamped on that. Not sure why he ordered a test for Lactate Dehydrogenase? And AntiNeutrophil Cytoplasmic Antibody? Also ordered Na/K/Creatine, kidney function?

He said he took a very aggressive attitude to PSC. So do I! It make me very angry!

At the April meeting in Pittsburgh Dr Lindor said that Urso and Silymarin (the herbal remedy milk thistle) are the only drugs proven to have therapeutic effects for PSC. Many liver patients take the latter and buy it over the counter. I don't think any docs prescribe it. It seems to have both an antifibrotic and TNF (Tumor Necrosis Factor) inhibitory effect. It's interesting that in Germany it's the remedy of choice for cases of death-cap mushroom poisoning. It seems 100% effective in people who eat this common poisonous mushroom. I think that in the US the survival rate is still less than 30%. Silymarin has not been approved in medicinal form. (I got this from a useful little book - C.Wanjek, "Bad medicine; misconceptions and misuses revealed." 2003, Wiley and sons.) I don't know how relevant that is for us but it appears to have a protective effect and restores damaged liver cells in this case.

Ivor

[Guest guest]

Hi Ivor;

I wish more hepatologists would consider measuring anti-nuclear

cytoplasmic antibodies (ANCA)! There's evidence that the type of

antibodies might affect clinical features of PSC:

Roozendaal C, Van Milligen de Wit AW, Haagsma EB, Horst G, Schwarze

C, HH, Kleibeuker JH, Tervaert JW, Limburg PC, Kallenberg CG

1998 Antineutrophil cytoplasmic antibodies in primary sclerosing

cholangitis: defined specificities may be associated with distinct

clinical features. Am. J. Med. 105: 393-399.

The ANCA against the bacterial/permeability increasing protein is

particularly interesting, as it might contribute to the

proinflammatory environment in IBD patients, and may compromise

defense against bacterial infections:

Schinke S, Fellermann K, Herlyn K, Reichel PH, Fundke R, Stange EF,

Gross WL, Schultz H 2004 Autoantibodies against the

bactericidal/permeability-increasing protein from inflammatory bowel

disease patients can impair the antibiotic activity of

bactericidal/permeability-increasing protein. Inflamm. Bowel Dis.

10: 763-770.

I wonder whether ANCA against bactericidal/permeability-increasing

protein might define a group of patients who would benefit from

antibiotics?

I think that measuring kidney function should be routine, not only

for end-stage liver disease, but also in early stages, especially in

patients who are taking 5-aminosalicylates for control of ulcerative

colitis and Crohn's disease:

de Jong DJ, Tielen J, Habraken CM, Wetzels JF, Naber AH 2005 5-

Aminosalicylates and effects on renal function in patients with

Crohn's disease. Inflamm. Bowel Dis. 11: 972-976.

I would argue that doctors who consult the " internet " for the latest

information on PSC/IBD would be more likely to be informed about

recent developments than those who do not!

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

[Guest guest]

Ivor, thanks for posting this. I have questions about a couple of things.

to add:

MRCP: it is non-invasive, so is free of the complications ERCP can bring. It is

getting

better at detecting bile duct strictures and cholangiocarcinoma. For

maintenance, it seems

like periodic MRCP would be less risky than ERCP, which can always be performed

later to

dilate any strictures. MRI is still expensive in the US, but ERCP seems like it

would be even

more so. I got a bill for an MRCP a few years back- $3000, but I noticed my

insurer only

paid $800 and that squared the bill. Odd how health care is more expensive the

poorer

you are, but I digress.

Questions:

> ULTRASOUND: Annually?? 6-monthly for those with cirrhosis. Looking at

> spleen, liver, intrahepatic portal flow, duct dilatation etc.

My left lobe is severely atrophied and this shows up on MRCP and ERCP. But

according to

the technician, by ultrasound it scarcely looks abnormal. He was looking at my

ovaries at

the time but we were talking about PSC so he looked at the liver too for good

measure. So

unless the abnormalities you mentioned are suspected, is it worth doing

annually? Never

been a part of the plan for me.

> At the April meeting in Pittsburgh Dr Lindor said that Urso and Silymarin

> (the herbal remedy milk thistle) are the only drugs proven to have

therapeutic

> effects for PSC. It's interesting that

> in Germany it's the remedy of choice for cases of death-cap mushroom

> poisoning. It seems 100% effective in people who eat this common poisonous

mushroom.

I'd be interested in seeing papers on Silymarin/milk thistle and it's

effectiveness in PSC

management. I checked the PSC literature site and didn't find anything that

looked like a

clinical trial, though there's a lot on the topic in regard to other liver

diseases. Any

suggestions?

Martha (MA)