Autoimmune Antibodies in Children and Adolescents With Nonalcoholic Fatty Liver Disease

Abstract

Objectives: The clinical significance of autoantibody positivity in nonalcoholic fatty liver disease (NAFLD) in the absence of autoimmune hepatitis (AIH) remains uncertain. We aimed to determine the prevalence of autoantibodies in a pediatric cohort with biopsy-proven NAFLD and investigate the association between autoantibodies and NAFLD histologic grade.

Methods: Single-center, retrospective study of patients ≤21 years with biopsy-proven NAFLD from 2014 to 2019. Clinical and laboratory data were obtained within 90 days of liver biopsy. Autoantibody positivity was defined as serum titer ≥1:80 or units ≥20. Liver biopsies were evaluated for features of AIH, then scored for steatosis, hepatocyte ballooning, lobular inflammation, and NAFLD activity score (NAS) was calculated. Portal inflammation and fibrosis were scored separately. Multivariable logistic regression was used for continuous and binary outcomes.

Results: Sixty-seven subjects met inclusion criteria. Positive antinuclear antibody (ANA), antismooth muscle antibody (ASMA), antineutrophil cytoplasmic antibody (ANCA), anti-F-actin antibody (F-actin), anti-liver kidney microsomal (LKM) antibody, or any combination was observed in 43%, 39%, 19%, 13%, 0%, and 66% of subjects, respectively. After controlling for confounders, positive ANA and alanine aminotransferase (ALT) >80 had 4.6 greater odds of having an NAS ≥5 ( P = 0.035; 95% confidence interval [CI], 1.12-19.01). Autoantibody positivity resolution occurred in 10%-50% who underwent serial monitoring.

Conclusions: Autoantibodies, except LKM, were frequently encountered in our pediatric NAFLD cohort in the absence of AIH. ANA positivity with ALT may help clinically stratify pediatric patients with suspected NAFLD targeting those at greater risk for nonalcoholic steatohepatitis (NASH).