Mandorfer Mattias, Bucsics Theresa, Hutya Veronika, Schmid-Scherzer Karin, Schaefer Benedikt, Zoller Heinz, Ferlitsch Arnulf, Peck-Radosavljevic Markus, Trauner Michael, Ferenci Peter, Kneussl Meinhard, Reiberger Thomas
Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Department of Internal Medicine II and Pulmonology, Wilhelminenspital, Medical University of Vienna, Vienna, Austria.
United European Gastroenterol J. 2018 Jun;6(5):710-718. doi: 10.1177/2050640618764057. Epub 2018 Feb 28.
The natural history of adult liver disease due to α1-antitrypsin deficiency (A1AD) remains poorly understood.
We investigated whether heterozygosity for the Z-allele predisposes for the development of clinically significant portal hypertension (CSPH). Moreover, we aimed to non-invasively assess the prevalence of liver fibrosis and hepatic steatosis in adults with A1AD treated by pulmonologists.
SERPINA1 rs28929474 (Z-allele) was genotyped in 315 patients with CSPH (hepatic venous pressure gradient ≥10 mmHg; cases) and 248 liver donors (controls). In addition, 31 adults with A1AD (PiZZ/PiSZ) and 11 first-degree relatives (PiMZ/PiMS) underwent liver stiffness and controlled attenuation parameter (CAP) measurement.
Heterozygosity for the Z-allele was observed in 6.7% of patients with CSPH and 2.8% of liver donors. Thus, harboring the Z-allele was associated with increased odds of CSPH (odds ratio: 2.47; 95% confidence interval: 1.03-5.9; = 0.042). Among PiZZ/PiSZ patients, 23%/3% had liver stiffness values indicative of liver fibrosis ( ≥F2/ ≥F3). Interestingly, 65%/52% of PiZZ/PiSZ patients had CAP values indicative of hepatic steatosis ( ≥S1/ ≥S2).
Heterozygosity for the Z-allele predisposes for the development of CSPH, confirming its role as a genetic (co)factor in liver disease. Pi*ZZ/SZ patients rarely develop liver fibrosis ≥F3 during adulthood; however, liver fibrosis ≥F2 is common. Elevated CAP values hint at underlying hepatic steatosis, which might promote liver fibrosis progression.
α1抗胰蛋白酶缺乏症（A1AD）所致成人肝病的自然病程仍知之甚少。
我们研究了Z等位基因杂合性是否易导致临床上显著的门静脉高压（CSPH）的发生。此外，我们旨在无创评估由肺科医生治疗的A1AD成人患者肝纤维化和肝脂肪变性的患病率。
对315例CSPH患者（肝静脉压力梯度≥10 mmHg；病例组）和248例肝脏供体（对照组）进行SERPINA1 rs28929474（Z等位基因）基因分型。此外，对31例A1AD患者（PiZZ/PiSZ）和11例一级亲属（PiMZ/PiMS）进行肝脏硬度和受控衰减参数（CAP）测量。
CSPH患者中6.7%和肝脏供体中2.8%观察到Z等位基因杂合性。因此，携带Z等位基因与CSPH发生几率增加相关（比值比：2.47；95%置信区间：1.03 - 5.9；P = 0.042）。在PiZZ/PiSZ患者中，23%/3%有提示肝纤维化的肝脏硬度值（≥F2/≥F3）。有趣的是，65%/52%的PiZZ/PiSZ患者有提示肝脂肪变性的CAP值（≥S1/≥S2）。
Z等位基因杂合性易导致CSPH的发生，证实其作为肝病遗传（共）因素的作用。Pi*ZZ/SZ患者在成年期很少发生≥F3的肝纤维化；然而，≥F2的肝纤维化很常见。升高的CAP值提示潜在的肝脂肪变性，这可能促进肝纤维化进展。
