Histopathology of Pediatric Nonalcoholic Fatty Liver Disease * #

Abstract

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-

Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis

“…Diagnosis of NASH was formulated in 38 patients (NASX5), a diagnosis of simple steatosis (NASp2) was made in 41 patients; whereas 41 were considered indeterminate. When the criteria of Schwimmer et al 27 were applied, only 3% patients met the criteria for NASH type 2 diagnosis, and 30% children encountered the criteria for NASH type 2. Most patients showed an overlapping of NASH types 1 and 2 (54%).…”

“…16,27 The syndrome occurs in 4.2% of healthy adolescents. 28 Its prevalence increases to 6.1 and 28.7% in overweight and obese adolescents, respectively, 27 and, according to this report, it achieves the rate of 66% in children with fatty liver disease.…”

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…The estimated NAFLD prevalence was 9.6% when adjusted for age, gender, race and ethnicity. 184 Multivariate analyses showed that obesity, older age (in adolescence), male gender, and Hispanic ethnicity are independent predictors of fatty liver prevalence.…”

“…Children are reported with NAFLD as early as 2 years and with NASH-related cirrhosis as early as age 8. 183,184 Prevalence and Risk Factors…”

The Histopathology of Pediatric Nonalcoholic Fatty Liver Disease * #

“…3 One hundred consecutive liver biopsies from children ages 2 to 18 years were reviewed. Ninety-eight percent of the children were either obese or overweight and 8% were diabetic.…”