الفهرس 
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Abstract
Hepatic steatosis among children has been increasing worldwide due to sedentarily life style, obesity and consumption of fast food. Diagnosis of the underlying cause of steatosis in liver biopsy constitutes a challenge in distinguishing simple steatosis from a more complex disorder. In the pediatric age group, steatosis is associated mainly with metabolic storage disease (inborn error of metabolism, IEM), fatty liver disease, viral infection, autoimmune hepatitis and drug-induced liver injury.
Liver biopsy is the gold standard for diagnosing the cause of steatosis. Interestingly, no pharmacological agents could be given to patients with steatosis unless appropriate diagnosis is reached by liver biopsy. In practice, pediatric liver histopathologists face a real problem in diagnosing the cause of steatosis. Pediatric liver biopsy with steatosis may be due to simple steatosis that should be monitored so that the condition does not progress into steatohepatitis/fibrosis/cirrhosis sequelae. Simple steatosis in pediatric liver biopsy may be part of the spectrum of a metabolic liver disease such as glycogen storage disease, Wilson disease, alpha 1 antitrypsin deficiency disease or others. In this situation, pediatric hepatologists have to look for a list of error of metabolism conditions to find out the exact cause of steatosis. Moreover, simple steatosis may be due to drug induced hepatitis.
Recently, autophagy has been implicated in the pathogenesis of fatty liver diseases, whether inborn error of metabolism or nonalcoholic steatohepatitis.
For this purpose, this study was designed in order to identify the etiologies underlying hepatic steatosis in pediatric liver biopsies and evaluate the role of autophagy markers in their pathogenesis.
We selected pediatric cases with steatosis from the archives of the pathology department, National Liver Institute, Menoufia University. Pathological diagnosis was correlated with clinical diagnosis from Pediatric hepatology department. Paraffin blocks from liver biopsies of selected cases were retrieved, reexamined and stained with autophagy markers Beclin1, LC3A and Sirt1 antibodies for immunohistochemisrty. Twenty one pediatric liver biopsies with no steatosis were used as a control group for immunohistochemistry.
Results from this study revealed that inborn error of metabolism (IEM) constituted 36 cases (44.5%) and included glycogen storage disease, Wilson disease, lipid storage disease, hemochromatosis, alpha 1 antitrypsin deficiency, mitochondrial cytopathy and tyrosinemia. Whereas, the chronic liver disease (CLD) group that showed steatosis in pediatric liver biopsies were 45 cases (55.5%) with different underlying etiologies. The most striking result to emerge from the data was the remarkably higher prevalence of fatty liver disease. Fatty liver disease (including cases of chronic hepatitis of undetermined etiology, steatohepatitis and simple fatty liver) accounted for 21 cases (25.9%), autoimmune hepatitis were 12 (14.8%), chronic viral hepatitis were 11 cases (13.6%) and one case (1.2%) drug-induced liver injury.
The IEM group revealed younger age at presentation (2-192 months), with statistical significant association with obesity, hepatosplenomegaly and hepatocyte ballooning in liver biopsy than CLD group.
Immunohistochemical results of Beclin 1 in the studied cases revealed reduced Beclin 1 in pediatric liver biopsies with IEM than in CLD and control normal liver tissues. Both Beclin 1 positivity and intensity were statistically significantly higher in CLD and control group than in IEM group.