Presence of Alpha 1 Antitrypsin Risk Variants is Not Associated with Histologic Severity of Pediatric NAFLD

Maya Khan, Corie Klepper, Sarah Orkin, Ana Catalina Arce-Clachar, Kristen Bramlage, Lin Fei, Alexander Miethke, Rohit Kohli, Stavra Xanthakos, Marialena Mouzaki

Research output: Contribution to journalArticlepeer-review


Background: Among adults with nonalcoholic fatty liver disease (NAFLD), alpha-1-antitrypsin (A1AT) heterozygosity has been linked to advanced liver disease; pediatric data remain unclear. Objective: The objective of this study is to determine whether A1AT PiZ or PiS variants are associated with liver disease severity in youth with NAFLD. Methods: Retrospective study of youth with confirmed NAFLD. Multivariable logistic regression used to determine independent associations between A1AT risk variants and histologic severity [NAFLD activity score (NAS) ≥5 and/or significant fibrosis (stage ≥2)]. Results: The cohort included 269 patients, mean age 12 [±3] years with NAFLD and A1AT phenotyping (n = 260) and/or A1AT levels (n = 261). The mean NAS of the cohort was 4.2 [±1.5]; 50% had any, and 18% had significant fibrosis. Most (86%) had the MM A1AT phenotype, while 7% had the MS and 3% the MZ phenotype (the rest had other, nonpathogenic variants). Mean A1AT level was 123 mg/dL [±20]. A1AT levels did not differ by low versus high NAS (122 ± 2 vs 126 ± 19 mg/dL, P = 0.12) or by no/mild versus significant fibrosis (123 ± 20 vs 126 ± 20 mg/dL, P = 0.23, respectively). Carriers and noncarriers of the PiS or PiZ variants had similar NAS (mean NAS 3.8 ± 1.6 vs 4.2 ± 1.4; P = 0.25, respectively). Fibrosis severity did not differ by carrier vs noncarrier group: 38% versus 52% had any fibrosis (P = 0.17) and 14% versus 18% had significant fibrosis (P = 0.80, respectively). Multivariable modeling showed no association between A1AT risk variants and histologic severity. Conclusion: While not uncommon, carriage of the A1AT PiZ or PiS risk variants was not associated with histologic severity in children with NAFLD.

Original languageEnglish (US)
Pages (from-to)166-170
Number of pages5
JournalJournal of pediatric gastroenterology and nutrition
Issue number2
StatePublished - Aug 1 2023


  • children
  • liver disease
  • nonalcoholic steatohepatitis
  • obesity

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health


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