Rapid Progression of NASH in Childhood

Abstract

Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) have been recognized entities in adult and pediatric medicine for more than 2 decades (1,2). Long-term follow-up studies of adults with NASH have confirmed that fibrosis can progress to cirrhosis (3). Individuals with NAFLD who have hepatic fibrosis and/or inflammation at presentation can progress to more severe fibrosis or cirrhosis and have a higher mortality when compared with individuals with steatosis alone (4–6). Nonalcoholic fatty liver disease is recognized as the most common cause of elevated liver enzymes in children. A recent autopsy series demonstrated that the estimated prevalence of NASH was 2.96% (22/742) in children. Furthermore, 23% of children with NAFLD in this study had NASH, whereas bridging fibrosis or cirrhosis was seen in 9% of children with NASH in this study (7). Long-term natural history data of pediatric NAFLD or NASH are not available. Certain components of routine laboratory tests may be predictive of NAFLD pattern and advanced fibrosis, but these serologic markers do not at present have adequate sensitivity or specificity to replace liver biopsy data to distinguish NASH from NAFLD (8). Serum alanine aminotransferase (ALT) and aspartate animotransferase (AST), for example, are not reliable measures of histological improvement in NASH (9). Thus, liver tissue histology becomes a critical requirement for accurate diagnosis and evaluation of fibrosis progression in patients with NAFLD or NASH. The invasive nature and inherent risk of percutaneous liver biopsy, coupled with the debatable benefit of liver biopsies in guiding therapy or changing clinical outcomes, have prevented gaining a full understanding of the natural history and progression rates of NASH in both children and adults. This report presents 2 children with NASH whose serial liver biopsies demonstrate progression of hepatic fibrosis in a short period of time. This report attempts to highlight that worsening of hepatic fibrosis can occur within childhood in patients with NASH.