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中国慢性乙型肝炎患者的自身抗体:患病率及临床关联

Autoantibodies in Chinese patients with chronic hepatitis B: prevalence and clinical associations.

作者信息

Li Bo-An, Liu Jia, Hou Jun, Tang Jie, Zhang Jian, Xu Jun, Song Yong-Ji, Liu Ai-Xia, Zhao Jing, Guo Jing-Xia, Chen Lin, Wang Han, Yang Li-Hua, Lu Jie, Mao Yuan-Li

机构信息

Bo-An Li, Jia Liu, Jun Hou, Jian Zhang, Jun Xu, Yong-Ji Song, Ai-Xia Liu, Jing Zhao, Jing-Xia Guo, Lin Chen, Han Wang, Li-Hua Yang, Yuan-Li Mao, Center of Clinical Laboratory Medicine, 302 Military Hospital of China, Beijing 100039, China.

出版信息

World J Gastroenterol. 2015 Jan 7;21(1):283-91. doi: 10.3748/wjg.v21.i1.283.

Abstract

AIM

To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB).

METHODS

A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested.

RESULTS

The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity.

CONCLUSION

ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.

摘要

目的

研究中国慢性乙型肝炎(CHB)患者自身抗体的流行情况及其与临床特征的关联。

方法

本项基于医院的回顾性研究共纳入325例中国CHB患者。纳入慢性丙型肝炎(CHC)、自身免疫性肝炎(AIH)或原发性胆汁性肝硬化(PBC)患者,并以健康供者作为对照。通过间接免疫荧光法和线性免疫分析法检测一组从血清学角度定义AIH和PBC的自身抗体。AIH相关自身抗体谱包括均质型抗核抗体(ANA-H)、平滑肌抗体、抗肝肾微粒体1型抗体、抗肝细胞溶质抗原1型抗体和抗可溶性肝抗原/肝胰抗体;PBC相关抗体以核点/膜缘样ANA、抗线粒体抗体-M2(AMA-M2)、抗BPO(AMA-M2靶向的重组抗原)、抗Sp100、抗早幼粒细胞白血病蛋白(抗PML)和抗gp210为特征。采用聚类二分法明确为每例患者指定AIH或PBC谱。同时检测抗Ro52抗体。

结果

CHB患者中任何一种自身抗体的流行率为58.2%,与CHC患者66.2%的流行率相似,显著高于健康对照的6.7%(P<0.001),低于AIH和PBC患者中100%的流行率(分别为P=0.004和P<0.001)。CHB患者中抗PML和抗gp210抗体比CHC患者更多(分别为11.1%对0%,P=0.003;12.6%对0%,P<0.001)。PBC患者中AMA、抗BPO、抗PML和抗gp210的流行率和滴度高于CHB患者。在CHB患者中,与无肝硬化患者相比,代偿期和失代偿期肝硬化患者ANA尤其是ANA-H的流行率显著降低。CHB患者中的38例肝细胞癌(HCC)患者与非HCC患者相比,抗PML的流行率有显著差异(0%对12.5%,P=0.013)。自身抗体二分法显示,PBC谱在CHB患者中比在CHC患者中更普遍,且与代偿期和失代偿期肝硬化均密切相关。相反,CHB非肝硬化患者中AIH谱的流行率显著高于代偿期肝硬化患者(18.5%对8.2%,P=0.039)。此外,AIH谱也与乙肝e抗原阳性密切相关。

结论

ANA-H可能是CHB早期阶段的一个指标。对自身抗体谱进行二分法分析显示,PBC谱与CHB肝硬化密切相关。

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