Nonalcoholic Steatohepatitis in Children

Abstract

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

Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity

“…Noteworthy, in children with NAFLD [32], [33] and [34], waist circumference was the only component of the metabolic syndrome associated with liver fibrosis. It is possible that this reflects the lower number of confounding factors in pediatric patients, i.e.…”

Dietary and physical activity patterns in children with fatty liver

“…In contrast, ALT may not be critical to disease definition in childhood NAFLD. Multiple case reports have shown that abnormal liver histology can be present in the face of normal serum ALTs (Carter-Kent et al, 2009). These children with fatty liver had lifestyle patterns (physical inactivity, high simple sugar/low PUFA intake) that lead to altered nutrient oxidation, energy imbalance, and changes in insulin sensitivity, all of which contribute to hepatic steatosis, and possibly to hepatocellular damage.…”

Nonalcoholic fatty liver disease: a challenge for pediatricians

“…It occurred more in male, Asian, Native American and Hispanic ethnicity. 6,26,28 Subsequent studies from Europe 33 and America 70 have demonstrated more frequent biopsy findings in the 'overlap' category (51 and 82%, respectively). This diversity in clinicopathological features suggests some pathophysiological differences between adult and pediatric NASH.…”

“…16,28,31 Another survey found some evidence of accompanying cardiovascular risks (metabolic syndrome) for live function test elevation to predict a severe fibrosis. 28,37,48,75,76 Therefore, usefulness of serum transaminase activities ratio was limited in predicting the severity of histological abnormality in NAFLD patients, 9,16,70,77,78 but not as diagnostic test of NAFLD, or in distinguishing NASH from NAFLD. 6,29,70 Table 2 presents results of some studies for diagnostic criteria based on plasma sample.…”

“…The prevalence (pretest odds or the probability of the disease state before test) of NASH has a range from 10 to77% overall and even 87% in obese children. 10,13,19,70 The post test odds (pretest odds  likelihood ratio) for a positive test (presence Pediatric nonalcoholic fatty liver K Widhalm and E Ghods of fibrosis) are a minimum of 53.35% and for a negative test are 4.85% (blue font). Consequently, unnecessary invasive test (liver biopsy) could be prevented at least in about half of the cases.…”