Abu Rmilah Anan, Fencl Robert, Watt Kymberly, Krowka Michael, Wiesner Russell, Murray David, Nyberg Scott, Leise Michael
William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine, Rochester, MN.
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN.
Transplantation. 2021 Jul 1;105(7):1576-1584. doi: 10.1097/TP.0000000000003390.
The role of MZ phenotype of α 1 antitrypsin (α1AT) deficiency as a potential cofactor in advanced liver disease arising from other primary causes is not widely understood. In the general population, MZ phenotype accounts for 2%-4% in Europe and 2%-7.1% in North America. The aim of this study was to determine the prevalence of the MZ phenotype among various causes of cirrhosis in the United States in the modern era and its impact on pulmonary function before and after liver transplantation.
This retrospective study included adult patients with cirrhosis who underwent liver transplantation at Mayo Clinic. Participants' data including pathogenesis of cirrhosis, model for end-stage liver disease-Na score, α1AT phenotype, liver decompensation events, and pulmonary outcomes was determined by retrospective review of the liver transplantation database.
One hundred thirty of 1341 adult patients with cirrhosis (9.7%) were α1AT MZ carriers. When comparing the distribution of protease inhibitor (PI) MZ among different pathogenesis, the prevalence of MZ was significantly increased in nonalcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), and cryptogenic cirrhosis compared with other causes. Thirty-seven of 171 with NASH (22%), 37 of 187 with ALD (20%), and 9 of 39 with cryptogenic cirrhosis (23.1%) were identified as PI MZ, while in other subgroups; we detected 18 of 320 with viral hepatitis, and 11 of 339 with primary biliary cholangitis/primary sclerosing cholangitis. Also, MZ patients were more likely to develop preoperative chronic obstructive lung disease, and postoperative pulmonary hypertension and pulmonary embolism than MM patients.
The rates of preoperative and postoperative pulmonary complications were found to be higher in PI MZ patients than in PI MM patients. The MZ phenotype was significantly enriched in NASH, ALD, and cryptogenic cirrhosis.
α1抗胰蛋白酶（α1AT）缺乏的MZ表型作为其他原发性病因所致晚期肝病的潜在辅助因素，其作用尚未得到广泛认识。在普通人群中，MZ表型在欧洲占2%-4%，在北美占2%-7.1%。本研究的目的是确定现代美国各种肝硬化病因中MZ表型的患病率及其对肝移植前后肺功能的影响。
这项回顾性研究纳入了在梅奥诊所接受肝移植的成年肝硬化患者。通过回顾肝移植数据库，确定参与者的数据，包括肝硬化的发病机制、终末期肝病-Na评分模型、α1AT表型、肝失代偿事件和肺部结局。
1341例成年肝硬化患者中有130例（9.7%）为α1AT MZ携带者。比较不同发病机制中蛋白酶抑制剂（PI）MZ的分布时，与其他病因相比，非酒精性脂肪性肝炎（NASH）、酒精性肝病（ALD）和隐源性肝硬化中MZ的患病率显著增加。171例NASH患者中有37例（22%）、187例ALD患者中有37例（20%）、39例隐源性肝硬化患者中有9例（23.1%）被确定为PI MZ，而在其他亚组中，320例病毒性肝炎患者中有18例，339例原发性胆汁性胆管炎/原发性硬化性胆管炎患者中有11例。此外，与MM患者相比，MZ患者术前更易发生慢性阻塞性肺疾病，术后更易发生肺动脉高压和肺栓塞。
发现PI MZ患者术前和术后肺部并发症的发生率高于PI MM患者。MZ表型在NASH、ALD和隐源性肝硬化中显著富集。
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