aDepartment of Gastroenterology, OLV Hospital, Aalst Departments of bHepatology cPathology dHuman Genetics eAbdominal Transplantation Surgery, University Hospitals Leuven, Leuven fHistocompatibility and Immunogenetics Lab, Mechelen, Belgium.
Eur J Gastroenterol Hepatol. 2013 Nov;25(11):1335-9. doi: 10.1097/MEG.0b013e32836171c4.
The Z allele (Glu342Lys) in α1-antitrypsin (AAT) deficiency is a combined deficiency and dysfunctional allele. Carrying one Z allele induces a risk of a more aggressive evolution in patients with a chronic liver disease. As most of the carriers of Z allele do not have overt liver disease, it is likely that Z allele-containing livers have been used previously for liver transplantation. We analyzed the incidence, epidemiology, and clinical features of AAT accumulation in the hepatocytes after liver transplantation.
Follow-up biopsies of liver transplant recipients were analyzed with periodic acid Schiff staining until 2006 (n=486); from 2006 on (n=303), all biopsies were stained with a specific monoclonal antibody against mutated AATZ protein. Genotyping of both recipient and donor was performed in the case of positive staining.
Of 789 liver transplantation patients, six patients (0.8%) showed mutated AATZ accumulation in the transplanted liver. Mutation analysis confirmed the presence of the Z allele in all donor organs including one transplanted organ with the SZ phenotype. There was a clear concordance between the isoelectrical focusing of the recipient AAT after transplantation and the genotype of the donor.
Presumed healthy donor organs containing the Z allele were used for transplantation in 0.8% of cases in our series. As the presence of a Z allele is an independent risk factor of aggravation of chronic liver disease, AATZ accumulation in biopsies after liver transplantation should be actively looked for.
α1-抗胰蛋白酶（AAT）缺乏症中的 Z 等位基因（Glu342Lys）是一个联合缺乏和功能异常的等位基因。携带一个 Z 等位基因会增加慢性肝病患者病情恶化的风险。由于大多数 Z 等位基因携带者没有明显的肝脏疾病，因此很可能之前就已经使用过携带 Z 等位基因的肝脏进行过肝移植。我们分析了肝移植后肝细胞中 AAT 积聚的发生率、流行病学和临床特征。
对肝移植受者的随访活检进行周期性酸-Schiff 染色分析，直至 2006 年（n=486）；自 2006 年起（n=303），所有活检均用针对突变型 AATZ 蛋白的特异性单克隆抗体进行染色。在染色阳性的情况下，对受者和供者进行基因分型。
在 789 例肝移植患者中，6 例（0.8%）患者的移植肝中出现突变型 AATZ 积聚。突变分析证实所有供体器官均存在 Z 等位基因，包括一个具有 SZ 表型的移植器官。受者移植后 AAT 的等电聚焦与供者的基因型之间存在明显的一致性。
在我们的研究系列中，0.8%的病例中使用了携带 Z 等位基因的假定健康供体器官进行移植。由于 Z 等位基因的存在是慢性肝病加重的一个独立危险因素，因此应积极寻找肝移植后活检中 AATZ 积聚的情况。
