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BOSTON -- Primary sclerosing cholangitis (PSC) is rare in children but when it appears it has a "chronic, progressive and relentless course," a researcher said here.

Half of all patients will develop some form of adverse liver event within a decade of diagnosis, even though most patients are treated with, according to , of the University of Utah in Salt Lake City.

And one in three will need a liver transplant, Deneau reported at the

The findings come from the first large international cohort of children, intended to characterize the long-term course of PSC, which Deneau said affects about 3 children in a million.

The size of the cohort is growing rapidly, however: The presentation was to be based on 500 children in 26 liver centers but Deneau and colleagues were able to add another 251 children and 10 centers in time for their presidential plenary session here.

Such a cohort is important because it will give clinicians more insight into the disease, commented association president , of the University of Michigan in Ann Arbor, who co-moderated the session.

"This is the first time we have assembled such a large number of children with a disease that is not very common," Lok told 名媛直播, "and it really shows the power of international collaboration."

The analysis showed "there really is a lot of variability" that would not show in small cases series and limited numbers, she said.

Getting the big picture "also allows you to look at predictors, why some children do better than others," Lok said. "When you have predictors, you can adjust treatment, you can focus on patients predicted to have a bad outcome."

Patients in the cohort had to have been younger than 18 at diagnosis, Deneau said, with either PSC alone or PSC with autoimmune hepatitis. They were excluded if they had secondary sclerosing cholangitis.

Patients were mostly male (61%), diagnosed on average at age 12, and been followed on average for 5.5 years. Three-quarters (76%) had inflammatory bowel disease, 33% had autoimmune hepatitis, and 83% were treated with ursodiol.

The investigators looked at a range of outcomes -- portal hypertensive complications such as varices, ascites, or encephalopathy; biliary strictures requiring intervention; cholangiocarcinoma; liver transplant; and death from liver disease -- as well as an endpoint composed of all five, Deneau said.

Among other things, they found:

• A steady progression to portal hypertensive complications, with 5% at diagnosis, 23% at 5 years, and 38% by 10 years. Such complications, Deneau said, are a "tipping point" -- 66% of patients will need a liver transplant within 5 years.
• The rate of biliary strictures requiring intervention also rose inexorably, from 4% at diagnosis to 14% after 5 years and 25% after 10 years.
• Cholangiocarcinoma was rare, occurring in 1% of patients (eight of the 751) and most of the patients (88%) were male. The condition was universally fatal if it was metastatic at diagnosis (in three cases) but resection or transplant rescued the other 5.
• Survival without liver transplant was 88% 5 years after diagnosis and 70% after a decade. The median age at transplant was 16.5
• Liver-related death was rare, afflicting just 11 of the 751 patients -- two with end-stage liver disease, three with cholangiocarcinoma, and six from post-transplant complications.

Interestingly, Deneau said in response to a question, there was little difference in event-free survival among patients with PSC alone and those with PSC combined with autoimmune hepatitis.

The disease is characterized by progressive inflammation, fibrosis, and structuring of the intrahepatic and extrahepatic bile ducts.

It isbut still rare: One review estimated the incidence at about 0.77 cases per 100,000 person-years, predominantly in men, with a median age at diagnosis of 41.

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