Elzouki A N, Eriksson S
Department of Medicine, Lund University, University Hospital, Malmö, Sweden.
Eur J Gastroenterol Hepatol. 1996 Oct;8(10):989-94. doi: 10.1097/00042737-199610000-00010.
To assess homozygous alpha 1-antitrypsin deficiency (PiZZ) as a risk factor for cirrhosis, hepatocellular carcinoma (HCC) and gallstone disease, and to analyse the respective interrelation-ships and those suggested to exist between PiZZ, alpha 1-antitrypsin and chronic hepatitis B and C.
DESIGN/METHODS: This study was based on 31 autopsied adults with severe alpha 1-antitrypsin deficiency diagnosed during the period 1963-94, in the city of Malmö, Sweden. For each autopsied PiZZ individual, four age- and sex-matched controls were selected from the same autopsy register. The autopsy rate during the study period was 57.2% of all deaths in the city and 85% of deaths at the hospital. Relative risks were estimated in terms of Mantel-Haenszel odds ratios (ORmh).
In the PiZZ group, we found 13 cases of cirrhosis (ORmh = 8.3; 95% CI, 3.8-18.3; P < 0.0001), 5 cases of HCC (ORmh = 5.0; 95% CI, 1.6-15.8; P = 0.008), and 8 cases of gallstone disease (ORmh = 1.0; 95% CI, 0.4-2.3; P = 0.924), compared with 7, 4 and 29 cases, respectively, in the control group. Stratification of the data by age and sex showed the difference in relative risk of cirrhosis between the PiZZ and control groups to be significant in both sexes, but that of HCC to be significant only in the male subgroup. There was no correlation between PiZZ state and gallstone disease in either sex. All PiZZ patients with cirrhosis and HCC had had negative tests for anti-hepatitis B core antigen and/or hepatitis B surface antigen. Of the homozygotes with cirrhosis or HCC for whom frozen sera were available (54% (7/13) and 60% (3/5), respectively), none had antihepatitis C antibodies, as tested both with ELISA-2 and RIBA-3. The prevalence of cirrhosis was higher in the PiZZ group than in controls for all ages above 50 years (P < 0.05). The occurrence of gallstone disease increased steadily with age in the two populations.
Although males and females with severe alpha 1-antitrypsin deficiency are not at significantly greater risk of gallstone disease, they are at greater risk of cirrhosis and HCC, the risk of HCC being more manifest in males. The risk of cirrhosis or HCC was unrelated to the presence of hepatitis B or C infection.
评估纯合子α1 -抗胰蛋白酶缺乏症（PiZZ）作为肝硬化、肝细胞癌（HCC）和胆结石疾病的危险因素，并分析PiZZ、α1 -抗胰蛋白酶与慢性乙型和丙型肝炎之间各自的相互关系以及可能存在的关系。
设计/方法：本研究基于1963年至1994年期间在瑞典马尔默市确诊的31例严重α1 -抗胰蛋白酶缺乏症的成年尸检病例。对于每例PiZZ尸检个体，从同一尸检登记册中选取四名年龄和性别匹配的对照。研究期间的尸检率为该市所有死亡人数的57.2%，医院死亡人数的85%。相对风险通过Mantel - Haenszel优势比（ORmh）进行估计。
在PiZZ组中，我们发现13例肝硬化（ORmh = 8.3；95%可信区间，3.8 - 18.3；P < 0.0001），5例HCC（ORmh = 5.0；95%可信区间，1.6 - 15.8；P = 0.008），以及8例胆结石疾病（ORmh = 1.0；95%可信区间，0.4 - 2.3；P = 0.924），而对照组分别为7例、4例和29例。按年龄和性别对数据进行分层显示，PiZZ组和对照组之间肝硬化的相对风险差异在两性中均显著，但HCC的相对风险差异仅在男性亚组中显著。在任何性别中，PiZZ状态与胆结石疾病均无相关性。所有患有肝硬化和HCC的PiZZ患者抗乙型肝炎核心抗原和/或乙型肝炎表面抗原检测均为阴性。对于有肝硬化或HCC且有冷冻血清可用的纯合子（分别为54%（7/13）和60%（3/5）），用ELISA - 2和RIBA - 3检测均未发现抗丙型肝炎抗体。50岁以上各年龄段的PiZZ组肝硬化患病率均高于对照组（P < 0.05）。在两个人群中，胆结石疾病的发生率均随年龄稳步上升。
虽然严重α1 -抗胰蛋白酶缺乏症的男性和女性患胆结石疾病的风险没有显著增加，但他们患肝硬化和HCC的风险更高，HCC的风险在男性中更明显。肝硬化或HCC的风险与乙型或丙型肝炎感染的存在无关。
