William F. Balistreri, MD


November 10, 2010

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Hello. I'm Dr. Bill Balistreri, Professor of Pediatrics at the University of Cincinnati College of Medicine and Cincinnati Children's Hospital. I'm here in Boston for the annual American Association for the Study of Liver Diseases (AASLD) Liver Meeting, and I'd like to review for Medscape some of the novel research related to pediatric liver disease.

Research presented this week offers new insight into what is the most vexing problem in pediatric hepatology: biliary atresia. This inflammatory fibro-obliterative disease of the bile ducts often leads to cirrhosis and, therefore, accounts for more than 50% of liver transplants done in children. The cause is not known, so this has been a very frustrating experience for those of us who must take care of these children. However, data presented here strongly suggest that bile duct injury in biliary atresia is due to a virus-induced autoreactive T-cell- mediated inflammatory insult. In several studies, animal models have shown that regulatory T-cell dysfunction and deficiency of hepatic CD4-positive cells appear to be important components of the cascade that leads to bile duct injury and, therefore, to the disease manifested as biliary atresia.

These observations certainly offer novel therapeutic approaches to this disease, as I mentioned, which is the most vexing problem that we must face. In a related clinical observation, results from a cross-sectional multicenter registry indicate that portal hypertension was present in 50% of 163 children with biliary atresia. This was manifested by variceal bleeding, ascites, hepatopulmonary syndrome, and/or splenomegaly. Compared with those children without portal hypertension, affected patients with biliary atresia had significant differences that could be measured. These were differences in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and bilirubin levels, and significantly lower white blood cell counts and platelet counts. It will be important to follow up this cohort of children. This will allow insight into the natural history of portal hypertension in biliary atresia and allow us to stage our therapeutic efforts.

Several studies here have focused on another cause of liver injury: drug-induced hepatotoxicity. While acute hepatotoxicity due to acetaminophen is well known, the impact of chronic, perhaps low-dose exposure to this drug, which is very widely used in children, is less well-appreciated. Data are emerging from a multicenter study that examined this issue. The biochemical profile of children with acute liver failure who had chronic exposure to acetaminophen was quite unique. It was characterized by lower bilirubin levels and higher peak ALT levels than patients with acute liver failure who did not have acetaminophen exposure. This gives us an important index by which to make an early diagnosis. In addition, the outcomes of these children were also worse than for those with single toxic exposure to acetaminophen. This observation should lead to enhanced recognition and hopefully to more effective preventive efforts to reduce exposure to this commonly used agent.

In another important observation, hepatitis E virus (HEV), which was previously thought to be uncommon in North America, is being increasingly recognized here as a cause of acute and perhaps chronic liver disease. At this meeting, a high prevalence of serologic evidence of HEV exposure was reported in children who had undergone liver transplantation. The investigators documented chronic inflammation, often leading to cirrhosis, which was presumably related to HEV infection occurring in an immune-compromised host. This report suggests that it may be time to screen for this agent, HEV, especially in high-risk children.

One final observation: as we all know, an emerging problem in children is fatty liver disease. This parallels the obesity epidemic. However, recognition of fatty liver disease and its consequences and certainly management of these children remains problematic. Studies presented here have documented that the combined use of 2 methods, the pediatric nonalcoholic fatty liver disease (NAFLD) fibrosis index and transient elastography (a measure of liver stiffness), can accurately detect the presence of significant fibrosis in children. These tools may offer a clinically useful noninvasive method to assess and monitor the progression to nonalcoholic steatohepatitis (NASH) in children with fatty liver disease.

In conclusion, the novel observations reported here this week will hopefully lead to transformation in our care of children with liver disease. I want to thank you for joining us. This is Dr. Bill Balistreri for Medscape.


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