Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P ‫؍‬ .009), hepatocellular ballooning (P ‫؍‬ .0001), lobular inflammation (P ‫؍‬ .0001), fibrosis (P ‫؍‬ .0001), and the absence of lipogranulomas (P ‫؍‬ .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of >5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH." (HEPATOLOGY 2005;41:1313-1321

Fatty liver is the most common liver abnormality in children age 2 to 19 years. The presence of macrovesicular hepatic steatosis in approximately 1 of every 10 children has important ramifications for the long-term health of children and young adults. The influence of the risk factors identified should be taken into consideration in the development of protocols designed to screen at-risk children and adolescents.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common in children and adolescents. However, standard histological criteria for pediatric NAFLD and NASH are undeveloped. We reviewed consecutive patients ages 2 to 18 years with biopsy-proven NAFLD diagnosed between 1997 and 2003. Biopsies were evaluated by two pathologists for individual features of steatohepatitis. Agglomerative hierarchical cluster analysis demonstrated two different forms of steatohepatitis. Type 1 was characterized by steatosis, ballooning degeneration, and perisinusoidal fibrosis; type 2 was characterized by steatosis, portal inflammation, and portal fibrosis. The study included 100 children with NAFLD. Simple steatosis was present in 16% of subjects, and advanced fibrosis was present in 8%. Type 1 NASH was present in 17% of subjects, and type 2 NASH was present in 51%. Boys were significantly (P < .01) more likely to have type 2 NASH and less likely to have type 1 NASH than girls. The NASH type differed significantly (P < .001) by race and ethnicity. Type 1 NASH was more common in white children, whereas type 2 NASH was more common in children of Asian, Native American, and Hispanic ethnicity. In cases of advanced fibrosis, the pattern was generally that of type 2 NASH. In conclusion, type 1 and type 2 NASH are distinct subtypes of pediatric NAFLD, and type 2 is the most common pattern in children. NASH subtypes should be considered when interpreting liver biopsies and planning studies of the pathophysiology, genetics, natural history, or response to treatment in pediatric NAFLD. ( NAFLD is likely the most common cause of chronic liver disease in children. 1 The major risk factors are obesity and insulin resistance, 2 and the prevalence of these risk factors has increased rapidly in children throughout the world. 3 NAFLD is rapidly becoming an important problem. Undiagnosed, this condition may progress silently and result in cirrhosis, portal hypertension, and liver-related death in early adulthood. 4 The characteristic histological features of NAFLD range from steatosis alone to steatohepatitis (NASH) with or without fibrosis to cirrhosis. In adults, the histological features of NAFLD have been well-described and include macrovesicular steatosis, perisinusoidal or pericellular fi-

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