Distinguishing Autoimmune Hepatitis From Steatohepatitis in Adolescents With Obesity and Positive Screening Alanine Aminotransferase

**Background:** Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children, while autoimmune hepatitis (AIH) is less prevalent but an important cause of liver-related morbidity and mortality. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend excluding other causes of liver disease when ALT is persistently >2 times the upper limit of normal, including testing for autoantibodies and IgG. However, autoantibodies are more common in children with obesity, and their presence alone is insufficient to diagnose AIH — liver histology is required. When NAFLD is diagnosed based solely on obesity and ultrasound findings of steatosis, AIH may be missed. This case series presents three adolescent females with obesity, elevated ALT, and ultrasound findings of steatosis, in whom thorough evaluation yielded three different diagnoses.

**Methods:** Three adolescent females (all age 15, BMI 30.0–32.3 kg/m², all at the 99th percentile) with elevated ALT detected through primary care screening were referred to pediatric gastroenterology for suspected NAFLD. Each underwent abdominal ultrasonography, which showed increased echogenicity suggestive of steatosis in all three. Each had normal hepatic synthetic function and was tested for viral hepatitis, Wilson’s disease, and alpha-1 antitrypsin deficiency (all negative). All three had positive ANA and underwent diagnostic liver biopsy.

**Key Results:** Patient A had ALT 187 U/L, ANA 1:80, anti-smooth muscle antibody 1:40, IgG 1306 mg/dL. Liver histology showed predominantly macrovesicular steatosis with mild chronic inflammation of portal tracts and stage 2 fibrosis, without plasma cells or interface hepatitis — consistent with nonalcoholic steatohepatitis. Patient B had ALT 74 U/L, ANA 1:1280, anti-smooth muscle antibody 1:320, IgG 2015 mg/dL. Histology showed a portal-based plasma cell-rich infiltrate with interface hepatitis and moderate macrovesicular steatosis with stage 1 fibrosis — consistent with both AIH and NAFLD. Patient C had ALT 179 U/L, ANA 1:640, anti-smooth muscle antibody <1:20, IgG 3067 mg/dL. Histology showed a portal-based plasma cell-rich infiltrate with interface hepatitis, no steatosis, and stage 3–4 fibrosis with early developing cirrhosis — consistent with AIH alone.

**Clinical Implications:** These cases highlight that AIH can present in adolescents with obesity and ultrasound evidence of steatosis, and that reliance on body habitus or imaging alone can lead to missed diagnoses. Although a BMI >98th percentile has been suggested as a breakpoint where autoimmune liver disease is less likely, both patients with AIH in this series had BMI at the 99th percentile. The authors note that in a prior study of 347 children referred for suspected NAFLD, 18% had a diagnosis other than NAFLD, with AIH being the most common alternative. They also cite data showing that 20%–40% of children evaluated for suspected NAFLD do not have autoantibodies tested, and that ultrasound has low specificity for NAFLD in children. The authors conclude that autoantibody testing is essential in the evaluation of elevated liver chemistry, ultrasound has inherent limitations as a measure of steatosis, and liver histology is required when more than one diagnosis remains in the differential based on noninvasive testing.