Non-alcoholic fatty liver disease in pediatric type 2 diabetes: Metabolic and histologic characteristics in 38 subjects

Background Obesity and type 2 diabetes (T2D) is risk factors for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In children with T2D and liver biopsies, we investigated correlations between NAFLD/NASH and transaminase activity, A1c, lipids, and histologic changes in repeat biopsies. Methods Liver histology of children with T2D was evaluated using the NASH CRN scoring system and NAFLD Activity Score (NAS). We included results <= 6 months from biopsy and A1c nearest biopsy. Results Thirty-eight subjects (21 females, 17 males, 63.2% Hispanic, 15.8% Caucasian) had T2D diagnosed at 13.4 +/- 2.7 years, 78.9% using metformin and 50% on insulin. Histological diagnosis of NAFLD occurred at mean age 14.3 +/- 2.3 years, notable for NASH in 61%. Steatosis grade was higher in children with NASH than those without (mean 2.6 +/- 0.7 vs 2.1 +/- 0.5 (P < 0.001). Stage 3 fibrosis was noted only in subjects with NASH (26%). ALT was higher in NASH vs those without (112 +/- 56 vs 85 +/- 112, P = 0.016). NAS correlated with A1c (r = 0.51, P < 0.01) and triglycerides (r = 0.5, P < 0.01), and inversely with high-density lipoprotein (HDL) (r = -0.42, P = 0.04). Males had lower HDL and higher triglycerides (P < 0.04). In eight subjects with repeat biopsies, NAS was equal (37.5%) or improved (62.5%), and steatosis decreased (68.1% to 32.8%, P = 0.027). Conclusions In children with T2D and NAFLD, NASH is common. Having advanced fibrosis in 26% of NASH cases at this age is concerning. Better control of lipids, weight, and diabetes may help avoid worsening in NAS.