Background & Aims The diagnostic accuracy of hepatic ultrasonography for detection and grading of hepatic steatosis in children with suspected nonalcoholic fatty liver disease (NAFLD) remains poorly characterized. The aim of this study was to prospectively evaluate the clinical utility of ultrasonographic quantification of hepatic steatosis. Methods Our cohort consisted of 208 consecutive pediatric patients with biopsy-proven NAFLD. Hepatic ultrasonography was performed within 1-month of the liver biopsy procedure. Steatosis identified by ultrasonography was scored using a 0 to 3 scale based on echogenicity and visualization of vasculature, parenchyma and diaphragm and compared to histological features based on Brunt’s classification. Results The median age at time of first visit was 10.8 years and 64% were boys. Sixty-nine percent had moderate to severe steatosis on histology. Ultrasonographic steatosis score (USS) had an excellent correlation with histological grade of steatosis (with a Spearman’s coefficient of 0.80). The area under the receiver operating characteristic (ROC) curve for ultrasonographic detection of moderate to severe steatosis was 0.87. The USS did not correlate significantly with inflammatory activity or fibrosis stage; however, there was significant correlation with the NAFLD activity score (NAS) albeit this was due in large part to the strong correlation with the steatosis component of NAS. Serum ALT and AST were not associated with histological grade of steatosis and showed no correlation with USS. Conclusions Our results, which represent the largest prospective pediatric study evaluating the role of hepatic ultrasonography in children with biopsy-proven NAFLD, demonstrate the utility of this technique for non-invasive diagnosis and estimation of hepatic steatosis in children.

Pathological increases in cell death in the liver as well as in peripheral tissues has emerged as an important mechanism involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). An increase in hepatocyte cell death by apoptosis is typically present in patients with NAFLD and in experimental models of steatohepatitis, while an increase in adipocyte cell death in visceral adipose tissue may be an important mechanism triggering insulin resistance and hepatic steatosis. The two fundamental pathways of apoptosis, the extrinsic (death receptor-mediated) and intrinsic (organelle-initiated) pathways, are both involved. This article summarizes the current knowledge related to the distinct molecular and biochemical pathways of cell death involved in NAFLD pathogenesis. In particular, it will highlight the efforts for the development of both novel diagnostic and therapeutic strategies based on this knowledge.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem worldwide. NAFLD represents a wide spectrum of conditions ranging from fatty liver, that in general follows a benign nonprogressive clinical course, to nonalcoholic steatohepatitis (NASH), a serious form of NAFLD, that may progress to cirrhosis and end-stage liver disease. The mechanisms responsible for NAFLD development and disease progression remain incompletely understood, but are of great clinical interest as current therapies are limited. Future therapies will be predicted based upon the understanding of its pathogenesis. This review focuses on the growing evidence from both experimental and human studies suggesting a central role of cytokines in the pathogenesis of NAFLD. We review the role of cytokines as key regulators of insulin sensitivity and hepatic lipid overloading, liver injury and inflammation, and fibrosis and cirrhosis, with an emphasis on potential therapeutic implications.

Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsyproven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS >5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P ‫؍‬ 0.003). Conclusion: Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. (HEPATOLOGY 2009;50:1113-1120

In pediatric IBD patients seen at a large, urban tertiary care facility in the United States, a significant minority (13%) have not been vaccinated against HBV. Nearly one-half of all patients (and 44% of previously vaccinated patients) did not have protective anti-HBs levels. Moreover, of those previously vaccinated, a significant minority (14%) appear at risk for HBV because protective anti-HBs levels were absent and could not be elicited through booster immunization. Given the high risk for severe HBV infection in this group, efforts should be made to screen for HBV immunity at the time of IBD diagnosis. Booster immunization should be considered in patients without protective antibodies.