From the Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
J Pediatr Gastroenterol Nutr. 2023 Aug 1;77(2):166-170. doi: 10.1097/MPG.0000000000003845. Epub 2023 May 25.
Among adults with nonalcoholic fatty liver disease (NAFLD), alpha-1-antitrypsin (A1AT) heterozygosity has been linked to advanced liver disease; pediatric data remain unclear.
The objective of this study is to determine whether A1AT PiZ or PiS variants are associated with liver disease severity in youth with NAFLD.
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)].
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.
While not uncommon, carriage of the A1AT PiZ or PiS risk variants was not associated with histologic severity in children with NAFLD.
在非酒精性脂肪性肝病（NAFLD）成人中，α-1-抗胰蛋白酶（A1AT）杂合性与晚期肝病有关；儿科数据仍不清楚。
本研究旨在确定 A1AT PiZ 或 PiS 变体是否与青少年 NAFLD 患者的肝病严重程度相关。
对确诊为 NAFLD 的青少年进行回顾性研究。多变量逻辑回归用于确定 A1AT 风险变体与组织学严重程度[非酒精性脂肪性肝病活动评分（NAS）≥5 和/或显著纤维化（分期≥2）]之间的独立关联。
该队列包括 269 名平均年龄为 12[±3]岁的患者，进行了 NAFLD 和 A1AT 表型（n=260）和/或 A1AT 水平（n=261）检测。该队列的平均 NAS 为 4.2[±1.5]；50%有任何纤维化，18%有显著纤维化。大多数（86%）具有 MM A1AT 表型，7%具有 MS 表型，3%具有 MZ 表型（其余为其他非致病性变体）。平均 A1AT 水平为 123mg/dL[±20]。低 NAS 与高 NAS 之间的 A1AT 水平无差异（122±2 与 126±19mg/dL，P=0.12）或无/轻度纤维化与显著纤维化之间的 A1AT 水平无差异（123±20 与 126±20mg/dL，P=0.23）。PiS 或 PiZ 变体携带者与非携带者的 NAS 相似（平均 NAS 3.8±1.6 与 4.2±1.4；P=0.25）。纤维化严重程度与携带者与非携带者组之间无差异：38%与 52%有任何纤维化（P=0.17），14%与 18%有显著纤维化（P=0.80）。多变量建模显示 A1AT 风险变体与组织学严重程度之间无关联。
虽然并不少见，但在患有 NAFLD 的儿童中，携带 A1AT PiZ 或 PiS 风险变体与组织学严重程度无关。
