Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, USA.
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, USA; Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, USA.
Clin Liver Dis. 2018 Nov;22(4):643-655. doi: 10.1016/j.cld.2018.06.010. Epub 2018 Aug 22.
In homozygous ZZ alpha-1-antitrypsin (AAT) deficiency, the liver synthesizes large quantities of AAT mutant Z, which folds improperly during biogenesis and is retained within the hepatocytes and directed into intracellular proteolysis pathways. These intracellular polymers trigger an injury cascade, which can lead to liver injury. This is highly variable and not all patients develop liver disease. Although not fully described, there is likely a strong influence of genetic and environmental modifiers of the injury cascade and of the fibrotic response. With improved understanding of liver injury mechanisms, new strategies for treatment are now being explored.
在纯合子 ZZ 型α-1-抗胰蛋白酶（AAT）缺乏症中，肝脏合成大量突变型 Z 的 AAT，该蛋白在生物发生过程中折叠不正确，滞留在肝细胞内，并定向进入细胞内蛋白水解途径。这些细胞内聚合物触发损伤级联反应，从而导致肝损伤。这种情况具有高度变异性，并非所有患者都会发展为肝病。尽管尚未完全描述，但损伤级联反应和纤维化反应的遗传和环境修饰物可能具有很强的影响。随着对肝损伤机制的深入了解，目前正在探索新的治疗策略。
