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Alpha 1-antitrypsin Deficiency

The most common metabolic cause of  chronic liver disease in children is alpha 1-antitrypsin deficiency. These children may have presented in infancy with a high bilirubin which completely went away, the diagnosis may never have been made until they come into your office or in to the hospital in childhood and they’ve already developed.

Interestingly, the lung disease tends to occur quite late in alpha 1-antitrypsin deficiency, whereas the liver disease will present sometimes quite early. Sometimes the cirrhosis is fully established and portal hypertension with a non-jaundiced child with a big spleen and may be vomiting blood in the emergency room, is the first sign that this child had alpha 1-antitrypsin deficiency all along. Treatment? There really is none. It’s supportive care, if end-stage liver disease is already present, until you can get these children transplanted.

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.

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, which is the carrier protein, is low. You are going to do a 24 hour urine copper. That’s going to be really high. And you are going to have your local, friendly hepatologist do a liver biopsy and you will note that the liver copper content is quite elevated.

The presentation can be all over the map. It can present as acute fulminant hepatitis. If it does, the tip-off is that these children have acute hemolytic anemia in association with their fulminant liver failure. If you see that combination, think Wilson’s disease until proven otherwise. They may present as a chronic active hepatitis, cirrhosis, portal hypertension, variceal bleeding. They may be totally asymptomatic with just a moderately elevated transaminitis.

The treatment for Wilson’s disease depends on when your diagnose is, which is why early diagnosis is essential. If there is no cirrhosis you are going to treat these patients with chelating agents, like penicillamine. However, if fully developed cirrhosis has already occurred, or they are presenting to you in fulminant liver failure, you have no other option but liver transplantation.

Now what about chronic hepatitis that we cause? Well, there is a group of babies who are born, for various reasons, with short-gut syndrome with inability to be enterally fed who find themselves long-term on parenteral nutrition. And this is quite an important cause of chronic liver disease in these children.