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).

The etiology and differential diagnosis of “autoimmune hepatitis-like liver disease” in children: a single-center retrospective study

“…Low-titer autoantibodies are found in patients with hepatolenticular degeneration, who are not directly associated with liver function impairment, steatosis and fibrosis ( 23 ). Antibodies that are more specific to autoimmune hepatitis, such as anti-LKM1, are not present in patients with MAFLD ( 5 ). This is consistent with the results of this article, with only the AIH group showing positive anti-LKM1.…”

“…However, the titers of these autoantibodies tend to decrease within several months ( 4 ). In a pediatric metabolic dysfunction-associated fatty liver disease (MAFLD) cohort, one-third of patients were positive for autoantibodies ( 5 ). Primary biliary cholangitis (PBC) are often accompanied by positive autoantibodies such as AMA and ANA ( 6 ).…”

Update on antineutrophil cytoplasmic autoantibody vasculitis in children

“…Diagnosis is based on clinical and histopathological features. While ANCAs are present in most children with AAV (except EGPA), they are also prevalent in children with other conditions [11,12]. The 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides and 2010 EULAR/PRINTO/PRES classification criteria for GPA in childhood are widely used [13,14].…”

Reliability and reproducibility of antinuclear antibody testing in pediatric rheumatology practice

“…As many as 40% of children and teens report arthralgias at well-child visits ( 40 ), 30% report fatigue ( 41 ) and smaller numbers report unexplained fevers ( 18 ). The differential diagnosis for such symptoms is broad; many of these children have acute or chronic infections, non-rheumatologic autoimmune diagnoses, or other chronic illnesses ( 15 , 18 , 24 , 25 , 27 , 30 , 31 ). Uncommonly, an ANA may be identified during evaluation of a child who is ultimately diagnosed with a malignancy ( 28 , 29 ).…”