Significance of autoantibody seropositivity in children with obesity and non‐alcoholic fatty liver disease

Abstract

Background: Autoantibodies are frequently positive in adults with nonalcoholic fatty liver disease (NAFLD) without concurrent autoimmune hepatitis (AIH). The clinical significance of this is unknown in children. Objective: To determine the prevalence of autoantibody positivity in pediatric NAFLD and to evaluate its association with disease severity. Methods: Multicenter, retrospective study of patients ≤18 years of age with biopsy-confirmed NAFLD. Descriptive statistics were used and groups were compared using Wilcoxon-Mann Whitney or χ 2 testing, and multivariable logistic regression was used for binary or ordinal outcomes. Results: One hundred and thirty six patients with a median age of 14 years were included. The median body mass index Z-score was 2.5 (interquartile range 2.2, 2.6). Positive antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody, or any combination of autoantibodies were observed in 22%, 14%, 0%, and 33% of patients, respectively. The proportion of patients with a steatosis score ≥2 was significantly higher in those with positive ANA (P = .045). In the multivariable regression analysis, positive ANA was associated with increased odds of steatosis score ≥2 (odds ratio, 5.91; 95% confidential interval, 1.50-23.26), after controlling for potential confounders. No other significant histology differences were seen between the groups. Conclusions: Positive ANA and ASMA are common in children with NAFLD; however, anti-LKM positivity is not. ANA positivity is associated with more severe steatosis.

Autoimmune Antibodies in Children and Adolescents With Nonalcoholic Fatty Liver Disease

“…Patton et al (6) showed that ASMA positivity increased in parallel with increasing NAS and remained an independent predictor after multivariable analysis. Yodoshi et al (7) showed that children with autoantibody positivity had lower aminotransferase levels, but those with positive ANA were more likely to have severe steatosis; otherwise, there were no associations with histologic severity of disease.…”

Prevalence and Significance of Antinuclear Antibodies in Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

“…Article quality was evaluated by two researchers according to the assessment scale recommended by the Agency for Healthcare Research and Quality (AHRQ), which was suitable for cross-sectional/prevalence studies and encompassed 11 items with a maximum score of 11 points [22]. The quality of the literature was categorized as low quality (0-3), moderate quality (4-7), and high quality (8)(9)(10)(11).…”

“…Of these full-text articles, 4 were excluded for not providing necessary data, 3 were excluded because NAFLD in those studies was not diagnosed by liver biopsy, and 1 was excluded because the authors adopted their own higher cutoff value to define ANA positivity. Thus, 13 articles consisting of 2331 patients with NAFLD were included in the final meta-analysis (Figure 1) [11][12][13][14][23][24][25][26][27][28][29][30][31]. Table 1 outlines the detailed characteristics of the 13 included articles.…”

“…For example, a crosssectional study performed in Japan involving 54 patients with biopsy-proven NASH reported that 42.6% of patients had positivity for serum ANA [29]. In addition, another multicenter study of 135 pediatric patients with NAFLD diagnosed by histological evaluation performed in the USA revealed that 30 patients (22.2%) were positive for serum ANA [11]. Recently, a study with 388 biopsy-confirmed NAFLD patients from China found that the prevalence of ANA positivity was 12.9% [14].…”

“…Elevated serum ANA titers might also be present in NAFLD without the context of autoimmune diseases or autoimmune hepatitis (AIH) [7]. For MAFLD-related management guidelines, high titers of ANA in patients with suspected liver fat infiltration would indicate that steatosis may be concurrent with or secondary to AIH, and further liver biopsy would be considered recommended for diagnosis [1,3,[8][9][10][11]. Since the production of autoimmune antibodies, including ANA, was theoretically stimulated by several proinflammatory cytokines during humoral immune responses, there would be a possible biological impact of serum autoantibody positivity contributing to liver damage progression in NAFLD by activating hepatic macrophagocytes and stellate cells.…”