Elzouki A N, Verbaan H, Lindgren S, Widell A, Carlson J, Eriksson S
Department of Medicine, University of Lund, University Hospital, Malmo, Sweden.
J Hepatol. 1997 Jul;27(1):42-8. doi: 10.1016/s0168-8278(97)80278-4.
BACKGROUND/AIMS: This study aimed to determine whether deficiency of the major serine protease inhibitors (alpha1-antitrypsin (AAT) or alpha1-antichymotrypsin (ACT)) is associated with increased risk for chronic hepatitis B or C virus (HBV or HCV) infection.
We studied 709 adults with chronic liver disease who had undergone liver biopsy during the 14-year period 1978-92. Anti-HCV testing was carried out with second-generation ELISA and immunoblot assays (RIBA 2). HBV markers were tested with commercially available radioimmunoassays. ACT and AAT concentrations in plasma were measured with electroimmunoassay and immune nephelometry. Plasma samples were screened for the AAT PiZ deficiency with ELISA technique and phenotyped by isoelectric focusing. The 229Pro-->Ala mutation for ACT deficiency was identified by PCR techniques.
Of the 709 patients, 132 (18.6%) were positive for anti-HCV according to RIBA 2. PiZ AAT deficiency was found in 44 (6.2%) of patients (one PiZZ, 38 PiMZ, and PiSZ), while subnormal ACT levels were found in 33 (4.6%) patients, frequencies that were higher than expected in the general population (p=0.0375 and p<0.0001, respectively). Of the PiZ-carriers, 8/44 (18%) were found to be anti-HCV positive according to RIBA 2, as compared to 123/662 (19%) non-PiZ-carriers (p>0.05). One of these patients had cirrhosis, four chronic active hepatitis, and three chronic persistent hepatitis. In contrast, 17/33 (51.5%) of the patients with subnormal ACT were anti-HCV positive (OR=5.2, CI=2.6-10.6; p<0.0001). No relationship was found between HBV infection and AAT deficiency or subnormal ACT levels. Only one patient with subnormal ACT levels was heterozygous for the 229Pro-->Ala mutation of ACT deficiency. There was no significant difference in the histological findings when the patients with subnormal ACT levels or PiZ allele were subgrouped according to HCV status.
There is no overrepresentation of chronic HBV or HCV in heterozygous AAT deficiency, although an association with more severe liver disease in such patients cannot be excluded. In contrast, low plasma levels of ACT that may be acquired or hereditary, due to mutations other than 229Pro-->Ala, are frequent in HCV infection.
背景/目的：本研究旨在确定主要丝氨酸蛋白酶抑制剂（α1-抗胰蛋白酶（AAT）或α1-抗糜蛋白酶（ACT））缺乏是否与慢性乙型或丙型肝炎病毒（HBV或HCV）感染风险增加相关。
我们研究了1978年至1992年这14年间接受肝活检的709例慢性肝病成人患者。采用第二代酶联免疫吸附测定（ELISA）和免疫印迹分析（RIBA 2）进行抗HCV检测。使用市售放射免疫测定法检测HBV标志物。采用电免疫测定法和免疫比浊法测量血浆中ACT和AAT浓度。用ELISA技术筛查血浆样本中的AAT PiZ缺乏，并通过等电聚焦进行表型分析。采用聚合酶链反应（PCR）技术鉴定ACT缺乏的229Pro→Ala突变。
在709例患者中，根据RIBA 2检测，132例（18.6%）抗HCV呈阳性。44例（6.2%）患者（1例PiZZ、38例PiMZ和PiSZ）存在PiZ AAT缺乏，而33例（4.6%）患者ACT水平低于正常，这些频率高于一般人群的预期（分别为p = 0.0375和p < 0.0001）。在PiZ携带者中，根据RIBA 2检测，8/44（18%）抗HCV呈阳性，相比之下，非PiZ携带者为123/662（19%）（p>0.05）。这些患者中1例患有肝硬化，4例为慢性活动性肝炎，3例为慢性持续性肝炎。相比之下，ACT水平低于正常的患者中有17/33（51.5%）抗HCV呈阳性（比值比（OR）=5.2，可信区间（CI）=2.6 - 10.6；p < 0.0001）。未发现HBV感染与AAT缺乏或ACT水平低于正常之间存在关联。只有1例ACT水平低于正常的患者为ACT缺乏的229Pro→Ala突变杂合子。根据HCV状态将ACT水平低于正常或携带PiZ等位基因的患者分组时，组织学结果无显著差异。
杂合性AAT缺乏中慢性HBV或HCV并无过多表现，尽管不能排除此类患者中存在与更严重肝病的关联。相比之下，由于229Pro→Ala以外的突变导致的可能为获得性或遗传性的低血浆ACT水平在HCV感染中很常见。
