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Primary Sclerosing Cholangitis

Primary sclerosing cholangitis is defined as chronic inflammation, resulting in a fibrotic narrowing and beading of the bile ducts, both inside and outside the liver primary sclerosing cholangitis. We really don’t know what causes primary sclerosing cholangitis. We do know that it’s associated with ulcerative colitis, and very often these children present somewhat subtly; fever, belly aches, but not always with jaundice. The liver, interestingly for chronic liver disease is usually enlarged and if you’ve got somebody who you think has got chronic liver disease and they have a big liver, you might think about primary sclerosing cholangitis.

The way you make the diagnosis is you do a cholangiogram and you see these beaded bile ducts, both inside and outside the liver. When you do the laboratory tests the thing that is going to stand out is that the alkaline phosphatase, a biliary canaliculi enzyme.

Transaminases will be up some and so might the bilirubin. We really don’t have a particularly effective treatment for this except for using synthetic bile acids like ursodeoxycholic acid, which may buy you some time. But some of these children will inevitably go on to end-stage liver disease and this is the other disease in which cholangiocarcinoma is highly associated. So some of these children, if you diagnose them in childhood, by the time they get to their 20’s and 30’s you are getting very nervous about them developing cholangiocarcinoma. Again, liver transplantation may certainly be indicated if they develop end-stage liver disease.

Secondary sclerosing cholangitis is kind of an interesting thing. It looks pretty much the same as primary sclerosing cholangitis. But you see it in association with other autoimmune diseases and other immunodeficiency-type syndromes. The one that we think of is Langerhans Cell Histiocytosis, which is often associated - even though it’s a rare disease in itself - with secondary sclerosing cholangitis.

Alpha 1-antitrypsin deficiency. The metabolic causes of chronic liver disease in children, by far and away the most common is alpha 1-antitrypsin deficiency. And if you remember, this is, generally speaking, associated with the ZZ phenotype. Occasionally you see it with some of the other phenotypes like MZ, but for purposes of keeping life simple, it’s the ZZ phenotype, generally speaking. As I said before, these children may have presented in infancy with a high bilirubin which completely went away.

Cystic fibrosis. You normally think about this as being a disease involving the lungs. Interestingly, cirrhosis with portal hypertension can occur in cystic fibrosis, generally presenting in mid or older age children. Sometimes the liver disease is much more important than the lung disease in these children, and they may also present with portal hypertension and already developed cirrhosis. If they’ve got portal hypertension, you try to shunt some of these children if they are big enough, because of course we are very worried about transplanting children who may already have chronic lung disease.

Wilson’s disease. You might only see one in your life but you sure don’t want to miss it. This is a disease which is marked by defective copper metabolism. You wind up with far too much copper in your liver, your central nervous system, and also in the kidney. The liver and the central nervous system are the two that really present to you most often, in terms of clinical symptoms. Now on the lab tests, what are you going to see? The serum copper is low and the serum ceruloplasmin.