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 โซุโฌ 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.)
N onalcoholic fatty liver disease is the most common form of chronic liver disease in both children and adults. 1,2 It is estimated that nonalcoholic fatty liver disease (NAFLD) affects about 20% to 30% of adults and 10% of children in the United States. 3,4 NAFLD represents a wide spectrum of conditions ranging from fatty liver to nonalcoholic steatohepatitis (NASH) to advanced fibrosis and cirrhosis. 5 Steatosis without significant liver cell injury or fibrosis is the most common form of NAFLD in both adults and children. 1,2 Studies in the adult population have variably suggested that steatosis is a benign nonprogressive condition, and NASH is recognized as a potentially serious condition with significant risk of morbidity and mortality. [6][7][8][9] Liver biopsy remains the standard for establishing the diagnosis of NASH. 10,11 The histological criteria for NASH in the adult population have evolved over the last two decades since the seminal publication of Ludwig et al. 12 The principal histological features of adult NASH include the presence of macrovesicular steatosis (characterized by a single or a few large droplets of fat and displacement of the nucleus), ballooning degeneration of hepatocytes, and a mixed lobular inflammation with or without a degree of portal inflammation. 10,11 Other features that are commonly present include zone 3 perisinusoidal-pericellular fibrosis; Mallory-Denk bodies (Mallory's