Graziadei I W, Joseph J J, Wiesner R H, Therneau T M, Batts K P, Porayko M K
Liver Transplant Unit, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Hepatology. 1998 Oct;28(4):1058-63. doi: 10.1002/hep.510280421.
Controversy exists whether patients who are genetically heterozygous for 1-antitrypsin deficiency (1ATD), carrying a single PIZ allele, are at increased risk of developing chronic liver disease. In these investigations, we determined the prevalence of heterozygous 1AT phenotypes (PI MZ, PI SZ) in a well-characterized cohort of patients presenting with chronic liver failure before orthotopic liver transplantation (OLT). We analyzed data collected from all adult patients (n = 641) who underwent OLT at our tertiary referral center between March 1985 and December 1996. Study patients entered a prospective protocol designed to test for all known etiologies of liver disease. Complete testing including 1AT phenotyping was successfully performed in 599 adults. We compared the overall number of heterozygous PIZ carriers in our OLT cohort with established prevalence figures for general and regional American populations, and examined their distribution among various liver disease subgroups. Fifty-one patients were found to be heterozygous carriers of a single PIZ allele for 1AT. The predominant phenotype in our transplantation cohort was PI MZ, identified in 49 patients (8.2%), which is a significantly higher prevalence than that reported from previous American population studies (2%-4%). Additionally, a significantly greater number of PI MZ carriers existed in patients with cryptogenic cirrhosis compared with other liver disease categories (26.9%; P < .001). These data suggest that individuals carrying a single PIZ allele for 1AT may be at increased risk of developing cirrhosis and liver failure, even in the absence of an identifiable coexisting liver disease.
对于携带单个PIZ等位基因的α1-抗胰蛋白酶缺乏症（1ATD）基因杂合子患者是否患慢性肝病的风险增加，目前存在争议。在这些研究中，我们确定了在原位肝移植（OLT）前出现慢性肝衰竭的特征明确的患者队列中杂合子α1-抗胰蛋白酶表型（PI MZ、PI SZ）的患病率。我们分析了1985年3月至1996年12月期间在我们的三级转诊中心接受OLT的所有成年患者（n = 641）收集的数据。研究患者进入了一个旨在检测所有已知肝病病因的前瞻性方案。在599名成年人中成功进行了包括α1-抗胰蛋白酶表型分析在内的完整检测。我们将OLT队列中杂合子PIZ携带者的总数与美国一般人群和地区人群的既定患病率数据进行了比较，并检查了他们在各种肝病亚组中的分布情况。发现51名患者是α1-抗胰蛋白酶单个PIZ等位基因的杂合子携带者。我们移植队列中的主要表型是PI MZ，在49名患者中被鉴定出来（8.2%），这一患病率明显高于先前美国人群研究报告的患病率（2%-4%）。此外，与其他肝病类别相比，隐源性肝硬化患者中PI MZ携带者的数量明显更多（26.9%；P <.001）。这些数据表明，即使没有可识别的并存肝病，携带单个α1-抗胰蛋白酶PIZ等位基因的个体患肝硬化和肝衰竭的风险可能会增加。
