https://pubmed.ncbi.nlm.nih.gov/37229749/ Alpha1 antitrypsin
J Pediatr Gastroenterol Nutr. 2023 May 25.
doi: 10.1097/MPG.0000000000003845.Online ahead of print.

Presence of Alpha 1 Antitrypsin risk variants is not associated with histologic severity of pediatric NAFLD

Maya Zahid Khan 1, Corie Klepper 2, Sarah Orkin 2 3, Ana Catalina Arce-Clachar 2 3, Kristen Bramlage 2 3, Lin Fei 2 3, Alexander Miethke 2 3, Rohit Kohli 4, Stavra Xanthakos 2 3, Marialena Mouzaki 2 3

Abstract
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: 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, non-pathogenic variants). Mean A1AT level was 123 mg/dl [±20]. A1AT levels did not differ by low vs. high NAS (122 ± 2 vs 126 ± 19 mg/dl, p=0.12) or by no/mild vs. significant fibrosis (123 ± 20 vs 126 ± 20 mg/dl, p=0.23, respectively). Carriers and non-carriers 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 non-carrier group: 38% vs 52% had any fibrosis (p=0.17) and 14% vs 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.