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Autoimmune Liver Disease in Children

Autoimmune liver disease in children. Typically we think of this as a disease affecting adolescent females but we have seen it in boys, we have seen it in little children, even as young as two or sometimes even less, autoimmune liver disease, autoimune. Presentation, again, highly variable autoimmune liver disease. They may turn up with chronic liver disease and all the characteristic usual associations; cirrhosis, portal hypertension autoimmune liver disease. But where we sometimes see it, and it’s very bothersome when it occurs this way, as a cause of actual fulminant liver failure in sub-acute kind of presentation. Some of these little ones will need liver transplantation

The diagnostic clue is that if you look at the proteins in the blood, the total serum protein is going to be high and the serum albumin is going to be low and the reason for that is that there is a hypergammaglobulinemia. So if you see a low serum albumin, a high total protein and you are beginning to think about chronic liver disease, it might make you think about autoimmune.

Then there is a whole array of diagnostic markers that I am not going to delineate for you; anti-smooth muscle, anti-mitochondrial antibodies, anti-liver-kidney microsomal. You can think about just about any antibody you want to and look for it as part of the way that you prove your diagnosis. Along, of course, with

The treatment, particularly if you are savvy and you make this diagnosis early, is

The mainstay is still steroids. You might add 6-MP, azathioprine or even some of the newer immunosuppressants to try and control the process. You have to remember that autoimmune diseases, no matter which one it is, are multi-system diseases so whether the presentation is in the liver or somewhere else, you should look at the joints, you look for funny rashes, you look for ulcerative colitis and Crohn’s disease, diabetes, thyroid problems. So don’t just stop at the liver. Make sure you have really carefully gone through all the other systems that

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. We are really not totally clear on the etiology but we do know that a chronic inflammatory process begins, progressing to fibrosis and then to 

Typically it’s in the neonates who cannot tolerate enteral feedings right from the get-go. So the more enteral feedings you can somehow or another get into these babies the more likely you are to protect their liver. We now see, unfortunately, more and more children referred to us who have short-gut syndrome whose livers have now gone into end-stage liver disease and who require a combined liver and intestinal transplant, if they have any

Then of course when you get to a lecture like this there are always the ones that we don’t understand. The so-called cryptogenics. This is probably a very interesting group of diseases and we are just not smart enough to know what they are. Probably some of them are autoimmune. We don’t know clearly what causes them but what we do know is that they can go all the way to end-stage liver disease and you find yourself transplanting a child and you have to

This is the end of the story, of the little boy you saw at the beginning with tyrosinemia. Here he is - I must add, three transplants later - and here’s his brother. Both children had hereditary tyrosinemia, both transplanted, both doing very nicely.

Alpha 1-antitrypsin deficiency. Turning away from the infections, 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, the diagnosis may never have been made until they come into your office or in to the hospital in

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 and all the problems of immunosuppression and

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 

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, and that’s the diagnostic test. So if you are worried about Wilson’s disease, get someone to do a liver biopsy on

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. Some of these children do present with the neurologic symptoms more than the liver symptoms and they can be very subtle. Changes in personality, school performance, behavior characteristics that the parents come in and say, "This just isn’t anything like the child I used to know." Be very aware of that.

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

Tyrosinemia. We heard about this in the infant age range. How about in children as a cause of chronic hepatitis? Tyrosinemia is an autosomal recessive disease. As we said, in infancy it is a fulminant presentation. In childhood, a chronic presentation. A very important thing about tyrosinemia in children is its association with hepatocellular carcinoma. Twenty-seven percent of children by their second birthday will already have HCC. So that’s why you really have to transplant these children, generally speaking, before the age of two in order to avoid this devastating complication. The other two systems that are involved are the central