TY - JOUR
T1 - Presence of Alpha 1 Antitrypsin Risk Variants is Not Associated with Histologic Severity of Pediatric NAFLD
AU - Khan, Maya
AU - Klepper, Corie
AU - Orkin, Sarah
AU - Arce-Clachar, Ana Catalina
AU - Bramlage, Kristen
AU - Fei, Lin
AU - Miethke, Alexander
AU - Kohli, Rohit
AU - Xanthakos, Stavra
AU - Mouzaki, Marialena
N1 - Publisher Copyright:
Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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.
AB - 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.
KW - children
KW - liver disease
KW - nonalcoholic steatohepatitis
KW - obesity
UR - http://www.scopus.com/inward/record.url?scp=85165521808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85165521808&partnerID=8YFLogxK
U2 - 10.1097/MPG.0000000000003845
DO - 10.1097/MPG.0000000000003845
M3 - Article
C2 - 37229749
AN - SCOPUS:85165521808
SN - 0277-2116
VL - 77
SP - 166
EP - 170
JO - Journal of pediatric gastroenterology and nutrition
JF - Journal of pediatric gastroenterology and nutrition
IS - 2
ER -