Re: Being candid about Candida ...Response to Lori and Taru-Mari

March 28, 2009

Dear Lori and Taru-Mari;

Sorry that the information contained in the abstracts is often so technical.

There's not much I can do about this except try to answer any questions that may

arise.

The term " stenosis " means a narrowing, and therefore means the same as a

" stricture " [the German group seems to prefer the term " stenosis " whereas in the

U.S. the term " stricture " is more often used]. So, both " stenosis " and

" stricture " mean narrowing of the bile-duct.

The term " dominant stenosis " or " dominant stricture " means a narrowing of the

main bile duct (the common bile duct) coming out of the liver, and/or a

narrowing of one or both of the main left and right branches from the common

bile duct inside the liver. Dr. Stiehl has his own very strict definition of a

" dominant stenosis " , and this is:

" A dominant stenosis was defined as a stenosis with a diameter of less than 1.5

mm of the common duct or less than 1.0 mm of a hepatic duct (within 2 cm of the

bifurcation) "

The term " bifurcation " refers to the branch point where the right and left

hepatic ducts join to form the main bile duct (common bile duct) that comes out

of the liver.

The above definition is from an earlier paper in which Dr. Stiehl's group first

documented Candida infections in PSC patients:

Kulaksiz H, Rudolph G, Kloeters-Plachky P, Sauer P, Geiss H, Stiehl A (2006)

Biliary candida infections in primary sclerosing cholangitis. J. Hepatol. 45:

711-716.

http://www.ncbi.nlm.nih.gov/pubmed/16979779

In this paper they note: " Candida disappeared spontaneously in 2/7 patients,

cleared after antifungal treatment in 2, and persisted in 3 patients. Patients

with biliary Candida had more severe cholangitis with higher CRP and serum

bilirubin compared to those without Candida infection. "

CRP means C-reactive protein, which is often used as a measure of inflammation.

In the full text of this paper they describe some of the antifungal treatments

attempted in these patients (Candida is a yeast which is a form of fungus):

" Three of the 8 patients with biliary Candida infection had clinical signs of

cholangitis and marked cholestasis and in addition to antibiotic treatment also

received antifungal treatment. One of these was treated with fluconazole,

Candida persisted despite treatment

and he died due to a cholangio-carcinoma after 2 months. The other two patients

were treated with caspofungine and Candida disappeared; in one of them the fungi

recurred after ending of treatment whereas

one patient had permanent clearance of the fungi. In the patient with permanent

clearance of Candida, cholestasis improved markedly and serum bilirubin

decreased from 8.8 to 2.2 mg/dl. By contrast, in the

patient with Candida recurrence cholestasis improved little and serum bilirubin

decreased only from 12.1 to 8.6 mg/dl. Both patients are scheduled for liver

transplantation. "

" Of the 5 patients not treated for fungal infection, in two Candida cleared

spontaneously, two continued to have Candida in bile and one patient was

transplanted. The two patients with Candida in their control bile have clinical

cholangitis with elevated CRP and serum bilirubin and currently are treated for

their fungal infection.

Apart from the fact that patients with Candida in bile belonged to the group of

patients with more severe cholestasis and higher serum bilirubin we did not find

any clinical signs which would be characteristic for this subgroup of patients. "

The abstract I posted yesterday is obviously a follow-up to this 2006 paper, and

they now come to the conclusion that the presence of Candida in bile IS a risk

factor for disease progression ( " Candida in bile is associated with a poor

prognosis and these patients need liver transplantation relatively soon " ). I

think you got this point (!!) but the " why " of this is more difficult to answer.

As I posted above, the Candida infections do not seem to be controlled in all

patients when treated with antifungal medications, such as fluconazole or

caspofungine, and it may be possible that the shorter time to transplantation in

patients with Candida infection is associated with poor response to these

antifungal therapies?

However, because I have not yet seen the full text of this article (my

subscription to J. Hepatol. has expired), I can't really comment much further on

this point. If anyone has a subscription to J. Hepatol. and can share this

recent paper, that would be much appreciated.

The abstract concludes that presence of a dominant stricture is a risk factor

for reduced survival free of liver transplantation ( " Survival free of liver

transplantation in patients without dominant stenosis at 18 years was 73.1% and

of patients with dominant stenosis was 25.0% (p=0.011) " ). This means there is an

approximately 3-fold higher risk of dying or needing a transplant in those

patients with a dominant stricture (compared to those without a dominant

stricture) during the 18-year period that these patients have been monitored.

The abstract concludes that bacteria in bile does not affect the risk for

survival free of transplantation provided that these infections are treated with

antibiotics and if dominant strictures are opened with endoscopic procedures

such as balloon dilatation during ERCP ( " Bacteria in bile do not worsen the

outcome if dominant stenoses are opened endoscopically and infection is

adequately treated with antibiotics. " ) What the abstract is NOT saying here is

that outcomes would probably be much worse if dominant strictures were not

opened endoscopically, and if bacterial infections were left untreated.

Best regards,

Dave

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

March 28, 2009

Dear Dave,

Thank you very much for kindly taking the time to explain this so well. Eemeli

does not have high bilirubin. His CRP is not routinely checked but the blood

sedimentation is regularly over the normal range indicating inflammation

somewhere. I guess one of the strictures is dominant because it is in one of the

major ducts, and the dr tried to open it and really took time in trying but did

not succeed in getting any instrument through it. And I guess Eemeli does not

have Candida because he did not get any antifungal medication. I am sure his dr

knows all about Adolf Stiehl's studies, it is just that the regular moms and

dads do not get the details of the findings the drs make, so we do not know

exactly what is going on (not sure if anyone nows EXACTLY what is going on in

the ducts but we do not get all the info the drs have). In 2006 I was still

working on getting Eemeli to be treated by drs that actually have some

experience on PSC and UC and he did not even have the UC diagnosis yet (although

he for sure had UC already), so I have missed the previous article about

Candida.

We are still waiting to hear what the verdict on Eemeli's colonoscopy biopsy is.

We should hear more next week on that, hopefully.

Once again, thank you very much Dave! Sorry to say I do not have a subscription

of J Hepatol but if I ever get one, I will be sure to share having it and any

information of interest.

Best wishes,

Taru-Mari, mom of Eemeli (12), PSC 7/2003 & UC 5/2008

PS. Apologies to all for occasionally forgetting to delete the message I am

responding to. The " trigger finger " hitting the enter button is too fast at

times.

March 28, 2009