Most recent PSC articles

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Curr Treat Options Gastroenterol. 2007 Mar;10(2):111-9.

Treatment of primary sclerosing cholangitis.

Rost D, Kulaksiz H, Stiehl A

Adolf Stiehl, MD Department of Medicine, University of Heidelberg,

Medizinische Universitatsklinik, Im Neuenheimer Feld 410, 69120

Heidelberg, Germany. adolf_stiehl@....

Aims of treatment for primary sclerosing cholangitis are as follows:

prevention of progression of hepatobiliary disease, reduction of

symptoms and consequences of cholestasis (pruritus, osteoporosis),

and prevention of complications (colorectal cancer, hepatobiliary

cancer). Ursodeoxycholic acid (UDCA) improves biliary secretion and

laboratory parameters of cholestasis, but its effects on liver

histology and survival are not clear. It reduces the incidence of

dysplasias and carcinomas of the colon in patients with colitis and

possibly has a beneficial effect on the incidence of bile duct

carcinomas. At present, UDCA represents the most promising

therapeutic option. Immunosuppressive treatment has not been proven

to be effective; it appears to be indicated in the overlap syndrome

with autoimmune hepatitis but may be harmful in bacterial

cholangitis. Bacterial cholangitis is common in patients with

dominant stenoses and requires antibiotic treatment. Endoscopic

treatment of dominant stenoses improves cholestasis and prolongs

survival in comparison to predicted survival. Pruritus represents a

problem in some patients, and cholestyramine represents the first-

line treatment. If ineffective, opioid antagonists, rifampin, or

ondansetron may be tried. For treatment of osteoporosis and

osteopenia, calcium and vitamin D supplementation are recommended,

and in selected cases, bisphosphonates may be indicated. In patients

with severe cholestasis and coagulation defects, parenteral

supplementation of vitamin K may be indicated. During treatment, all

patients should be regularly screened for colonic and bile duct

carcinomas. Patients with cirrhosis of the liver and its

complications are treated accordingly, and in end-stage disease,

liver transplantation is indicated. PMID: 17391626.

_______________________

Dig Dis Sci. 2007 Mar 28; [Epub ahead of print]

Helicobacter pylori May Play a Contributory Role in the Pathogenesis

of Primary Sclerosing Cholangitis.

Krasinskas AM, Yao Y, Randhawa P, Dore MP, Sepulveda AR

Department of Pathology, Division of Anatomic Pathology, University

of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Helicobacter pylori (H. pylori) DNA has been identified in human

livers and has been implicated in chronic liver disease and liver

cancer. To better understand the role of H pylori in primary

sclerosing cholangitis (PSC), 25 patients with end-stage PSC and 31

controls were studied. Genomic DNA was extracted from microdissected

hilar hepatic ducts of liver explants and was amplified for H pylori

DNA. Serum was tested for H pylori antibodies. Helicobacter DNA was

detected in 9 of the 56 (16%) patients by 16SrRNA PCR (an additional

case [for a total of 18%] was antibody positive). Seven of the 9

cases identified by polymerase chain reaction were positive for the

CagA gene, confirming they were H pylori. Seven of the 25 (28%)

patients with PSC and 3 of the 31 (9.7%) controls were positive for

Helicobacter (P=.087). H pylori DNA was detected in microdissected

hilar biliary epithelium in more PSC patients than controls,

supporting the hypothesis that bile reflux from the duodenum into the

biliary tract might carry H pylori organisms into the proximal

biliary system, possibly contributing to PSC development and/or

progression in some patients. PMID: 17393314.

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J Hepatol. 2007 Feb 27; [Epub ahead of print]

Particular genetic variants of ligands for natural killer cell

receptors may contribute to the HLA associated risk of primary

sclerosing cholangitis.

Karlsen TH, Boberg KM, Olsson M, Sun JY, Senitzer D, Bergquist A,

Schrumpf E, Thorsby E, Lie BA

Medical Department, Rikshospitalet-Radiumhospitalet Medical Center,

University of Oslo, Oslo, Norway; Institute of Immunology,

Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo,

Oslo, Norway.

BACKGROUND/AIMS: Combinations of killer immunoglobulin-like receptors

(KIRs) and HLA class I ligands that reduce natural killer (NK) cell

inhibition have been shown to increase risk for autoimmune diseases.

We aimed to clarify to what extent such combinations influence

susceptibility to primary sclerosing cholangitis (PSC). METHODS:

Three hundred and sixty-five Scandinavian PSC patients and 368

healthy controls were genotyped for the presence or absence of genes

encoding all KIRs using a PCR-SSP approach. KIR binding site

variation of HLA-A, -B and -C was also determined. RESULTS: The KIR

gene frequencies were similar among patients and controls. However,

the frequency of HLA-Bw4 and -C2, which are ligands for the

inhibitory KIRs 3DL1 and 2DL1, respectively, was significantly

reduced in PSC patients as compared with controls (38.2% vs. 54.7%, P

(corrected)[P©]=0.0006 and 42.7% vs. 56.9%, P©=0.009,

respectively). Two HLA risk haplotypes in PSC (carrying DRB1*0301 or

DRB1*1501, respectively) were devoid of both of these alleles, and

carried the 5.1 variant of the major histocompatibility complex class

I chain-related A (MICA) gene previously reported to influence PSC

susceptibility. CONCLUSIONS: Particular variants of ligands for NK

cell receptors encoded at three neighbouring genes in the HLA complex

may contribute to PSC associations observed in this genetic region.

PMID: 17383044.

Dave R.

[Guest guest]

-----Original

Message----- Current Treat Options

Gastroenterol.

Helicobacter

pylori May Play a Contributory Role in the Pathogenesis of Primary Sclerosing

Cholangitis.

Current Treatment Options?? Sorry, this is old, old news…… (to our group anyway!)

At least 6 or 7 years

ago, our very own group member Andi

came up with this conclusion!!

Way to go Andi! (Too bad we didn’t

call a bookie in Vegas and put money on it – we could have funded our own

registry and tons of research!)

Barb in Texas - Together in the Fight, Whatever it Takes!

Son Ken (32) UC 91 - PSC 99 Listed 7/21 @ Baylor Dallas

..