RE: Ursodiol and risk of cholangiocarcinoma

[Guest guest]

I

wish they had said what dosage was used.

Barb

in Texas

Ursodiol and risk of cholangiocarcinoma

The incidence of

cholangiocarcinoma in primary sclerosing cholangitis after long-time treatment

with ursodeoxycholic acid.

[Guest guest]

Hi Barb;

This is the preliminary report that appeared last year, and indicates

that the dose of ursodiol was gradually increased over the course of

the study:

Falk Symposium 155 XIII FALK LIVER WEEK (Part I) XIX International

Bile Acid Meeting. Bile Acids: Biological Actions and Clinical

Relevance, October 6 - 7, 2006 Freiburg (Germany), p. 90 (2006)

The incidence of cholangiocarcinoma in primary sclerosing cholangitis

during longtime treatment with ursodeoxycholic acid.

Stiehl A

Department of Medicine, University of Heidelberg, Germany

Introduction: Cholangiocarcinoma (CCA) represents a serious

complication of primary sclerosing cholangitis (PSC). In two recent

studies with 604 and 161 patients followed over a median time of 5.7

and 11.5 years the reported incidence rate of CCA was 13.3 and 6.8 %

(A Bergquist et al., J Hepatol 2002; 36: 321–327; K Burak et al.,

Am J Hepatol 2004; 99: 523–526). Ursodeoxycholic acid (UDCA) possibly

may influnce the incidence of CCA in man (B Brandsaeter et al. J

Hepatol 2004; 40: 815–822). Aim of study: The aim of the present

study was to evaluate the incidence rate of CCA in PSC patients after

longtime treatment with ursodeoxycholic acid. Patients and methods:

The present study was started in May 1987 and data up to May 2005

were considered in the evaluation. A total of 150 patients (105 men

and 45 women) with PSC but without evidence of CCA at entry were

included in the study. Of the patients included 101 had inflammatory

bowel disease (93 ulcerative colitis and 6 Crohn's disease).

Altogether 120 patients were treated for 1 year, 107 for 2 years, 97

for 3 years, 83 for 4 years, 72 for 5 years, 62 for 6 years and 57

for 7-18 years. Up to 1995 the patients were treated with UDCA in a

dose of 750 mg/d (8.8-15.3 mg/kg), starting from 1997 with 13.8–17.4

mg/kg and starting from 2001 with 18-20 mg/kg. A minority of 63

patients who were included in a study of UDCA absorption

intermittently received higher doses of up to 30 mg/kg for up to 3

months. All 72 patients with dominant stenoses were treated by

repeated endoscopic dilatation. Diagnosis of CCA was established in

each case by histologic examination of tissue obtained at laparotomy

or in the explanted liver at the time of liver transplantation.

Results: The median treatment time of the 150 patients was 6.4 years.

Altogether 5 patients developed a CCA during UDCA treatment yielding

an incidence rate of 3.3%. The calculation of CCA per patient years

revealed 0.58 CCA per 100 patient years in years 0-2.5, 0.49 CCA in

years 2.5-8.5, and no CCA thereafter up to 18 years after entry into

the study. The Kaplan Meier estimate of CCA incidence during UDCA

treatment reached a plateau after 8.3 years. All 5 patients with CCA

belonged to the subgroup of patients with colitis and in addition to

the subgroup of patients with dominant stenosis. Summary and

conclusion: The annual incidence rate of CCA in PSC treated with

UDCA is low and decreases with time of treatment. Compared with the

CCA incidence rates reported in studies on the natural course of the

disease, the CCA incidence after UDCA treatment was lower than

expected.

Dave R.

>

> I wish they had said what dosage was used.

>

> Barb in Texas

[Guest guest]

Hello ,

and thank you for that report. Looks like that urso makes the risk for CCA

clearly

smaller and that the risk does not automatically accumulate with the duration of

the

disease.

Would be of course interesting to get a bigger group of UC-patients studied,

because that

subgroup looks to have a more risky situation. How do you interpret this study;

urso

helps everybody, but UC-patients still have a bigger risk then only-psc-ers?

For me is interesting to see the names of southern Germany doctors like A.

Stiehl

mentioned on this field; the first time I was told about urso in combination

with psc was

in beginning of 90's when I lived for couple of years in that area.

Definitely would also be interesting to know how the research group in Graz,

Austria (M.

Trauner a.o.) is doing with 24-nor-udca, wonder if they are already in clinical

studies?

Propably we will have to wait a while with any news how it works in humans.

Results with

mice were encouraging, and international patent for human cholestatic diseases

has

already been made:

http://www.wipo.int/pctdb/en/wo.jsp?wo=2006119803

Best greetings,

, UC '83/small duct psc '83, large duct psc '93