HBV感染者HBsAg、抗-HBs双阳性对肝细胞癌发生影响的Meta分析

范梦洁; 曾争

doi:10.3969/j.issn.1001-5256.2019.08.015

HBV感染者HBsAg、抗-HBs双阳性对肝细胞癌发生影响的Meta分析

DOI: 10.3969/j.issn.1001-5256.2019.08.015

范梦洁,
曾争

北京大学第一医院感染疾病科

基金项目:

国家国际科技合作专项(2014DFR31200)；国家自然科学基金(30671855)；美国国家卫生研究院国家癌症研究所(N01-CO-12400)；

详细信息

中图分类号: R512.62;R735.7
计量
- 文章访问数: 479
- HTML全文浏览量: 20
- PDF下载量: 100
- 被引次数: 34
出版历程
- 收稿日期: 2019-04-03
- 出版日期: 2019-08-20

Influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma in patients with chronic hepatitis B: A Meta-analysis

Department of Infectious Diseases, Peking University First Hospital

Research funding:

摘要

摘要:
目的探讨HBV感染者HBsAg、抗-HBs双阳状态对肝细胞癌（HCC）发生的影响。方法检索PubMed、Embase、Cochrane Library英文数据库及中国知网、万方中文数据库1975年7月1日-2019年3月27日发表的有关血清HBsAg、抗-HBs双阳状态对HCC发生风险的文献。采用RevMan5. 3和Stata11. 2软件对纳入文献数据进行统计分析。对纳入的各研究进行异质性分析,如果各研究间存在显著异质性,则采用随机效应模型分析;若各研究间异质性不显著,则采用固定效应模型分析。比值比（OR）和相应的95%可信区间（95%CI）被用于评估HBsAg、抗-HBs双阳状态与HCC发生的关系。采用Begg漏斗图和Egger检验进行发表偏倚分析。通过每次去除一篇文献的敏感性分析方法评估Meta分析的质量和可信度。结果最终纳入4篇文献,其中2项研究来自韩国人群,2项研究来自中国人群,共3042例患者。Meta分析结果显示,HBsAg、抗-HBs双阳状态与HCC发生之间无显著性关联（OR=1. 46,95%CI:0. 76～2. 80,P=0. 25）。基于国别的亚组分析显示,在...
- 乙型肝炎,慢性 /
- 癌,肝细胞 /
- 乙型肝炎表面抗原 /
- 乙型肝炎抗体 /
- Meta分析(主题)
Abstract:
Objective To investigate the influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection. Methods PubMed, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for articles on the influence of dual positivity of HBsAg and anti-HBs on the risk of HCC published from July 1, 1975 to March 27, 2019. RevMan5. 3 and Stata11. 2 were used for statistical analysis of data. A heterogeneity analysis was performed for the studies included; a random effects model was used in case of significant heterogeneity, and a fixed effects model was used in case of non-significant heterogeneity. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to investigate the association of dual positivity of HBsAg and anti-HBs with the development of HCC. Begg funnel plots were used to investigate publication bias. By removing one article each time, the sensitivity analysis was used to assess the quality and reliability of the Meta-analysis. Results A total of 4 articles were included, with 2 studies in the Korean population and 2 in the Chinese population, and there were 3042 patients in total. The meta-analysis showed that there was no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC (OR = 1. 46, 95% CI: 0. 76-2. 80, P = 0. 25) . A country-based subgroup analysis showed significant association between dual positivity of HBsAg and anti-HBs and the development of HCC in the Korean population (OR = 2. 67, 95% CI: 1. 61-4. 43, P = 0. 000 1) , while no significant association was found in the Chinese population (OR = 0. 89, 95% CI: 0. 48-1. 64, P = 0. 70) . Conclusion There is no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC, and further studies are needed in future.
- hepatitis B, chronic /
- carcinoma, hepatocellular /
- hepatitis B surface antigens /
- hepatitis B antibodies /
- Meta-analysis as topic

HTML全文

参考文献(37)

[1] ZHOU J, SUN HC, WANG Z, et al. Guidelines for diagnosis and treatment of primary liver cancer in China (2017 edition) [J]. Liver Cancer, 2018, 7 (3) :235-260.

[2] LYU H, LEE D, CHUNG YH, et al. Synergistic effects of A1896, T1653 and T1762/A1764 mutations in genotype c2hepatitis B virus on development of hepatocellular carcinoma[J]. J Viral Hepat, 2013, 20 (3) :219-224.

[3] WANG GQ, ZHAO XM, LI XY, et al. Effect of high hepatitis B vaccine coverage on the incidence among inoculated populations[J]. Int J Virol, 2017, 24 (5) :336-338. (in Chinese) 王桂强, 赵旭明, 李秀燕, 等.乙型肝炎疫苗高覆盖率对接种人群发病的影响[J].国际病毒学杂志, 2017, 24 (5) :336-338.

[4] WHO. Global hepatitis report, 2017[EB/OL]. 2017:83. http://www. who. int/hepatitis/publications/global-hepatitisreport2017/en/.

[5] DING F, YU HG, LI YX, et al. Sequence analysis of the HBV S protein in Chinese patients with coexisting HBsAg and antiHBs antibodies[J]. J Med Virol, 2015, 87 (12) :2067-2073.

[6] XIANG Y, CHEN P, XIA JR, et al. A large-scale analysis study on the clinical and viral characteristics of hepatitis B infection with concurrence of hepatitis B surface or E antigens and their corresponding antibodies[J]. Genet Mol Res, 2017, 16 (1) .

[7] FU X, CHEN J, CHEN H, et al. Mutation in the S gene of hepatitis B virus and anti-HBs subtype-nonspecificity contributed to the co-existence of HBsAg and anti-HBs in patients with chronic hepatitis B virus infection[J]. J Med Virol, 2017, 89 (8) :1419-1426.

[8] HUANG X, QIN Y, ZHANG P, et al. Pre S deletion mutations of hepatitis B virus in chronically infected patients with simultaneous seropositivity for hepatitis-B surface antigen and antiHBS antibodies[J]. J Med Virol, 2010, 82 (1) :23-31.

[9] PU Z, LI D, WANG A, et al. Epidemiological characteristics of the carriers with coexistence of HBsAg and anti-HBs based on a community cohort study[J]. J Viral Hepat, 2016, 23 (4) :286-293.

[10] LEE BS, CHO YK, JEONG SH, et al. Nationwide seroepidemiology of hepatitis B virus infection in South Korea in 2009emphasizes the coexistence of HBsAg and anti-HBs[J]. J Med Virol, 2013, 85 (8) :1327-1333.

[11] HAYASHI J, NOGUCHI A, NAKASHIMA K, et al. Frequency of concurrence of hepatitis B surface antigen and antibody in a large number of carriers in Okinawa, Japan[J]. Gastroenterol Jpn, 1990, 25 (5) :593-597.

[12] TSANG TK, BLEI AT, O'REILLY DJ, et al. Clinical significance of concurrent hepatitis B surface antigen and antibody positivity[J]. Dig Dis Sci, 1986, 31 (6) :620-624.

[13] COLSON P, BORENTAIN P, MOTTE A, et al. Clinical and virological significance of the co-existence of HBsAg and antiHBs antibodies in hepatitis B chronic carriers[J]. Virology, 2007, 367 (1) :30-40.

[14] HEIJTINK RA, van HATTUM J, SCHALM SW, et al. Co-occurrence of HBs Ag and anti-HBs:Two consecutive infections or a sign of advanced chronic liver disease?[J]. J Med Virol, 1982, 10 (2) :83-90.

[15] JANG JS, KIM HS, KIM HJ, et al. Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection[J]. J Med Virol, 2009, 81 (9) :1531-1538.

[16] Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.

[17] HIGGINS JP, THOMPSON SG. Quantifying heterogeneity in a meta-analysis[J]. Stat Med, 2002, 21 (11) :1539-1558.

[18] MACASKILL P, WALTER SD, IRWIG L. A comparison of methods to detect publication bias in meta-analysis[J]. Stat Med, 2001, 20 (4) :641-654.

[19] QIAO Y, LU S, XU Z, et al. Additional N-glycosylation mutation in the major hydrophilic region of hepatitis B virus S gene is a risk indicator for hepatocellular carcinoma occurrence in patients with coexistence of HBs Ag/anti-HBs[J]. Oncotarget, 2017, 8 (37) :61719-61730.

[20] SEO SI, CHOI HS, CHOI BY, et al. Coexistence of hepatitis B surface antigen and antibody to hepatitis B surface may increase the risk of hepatocellular carcinoma in chronic hepatitis B virus infection:A retrospective cohort study[J]. J Med Virol, 2014, 86 (1) :124-130.

[21] FU XC, CHEN J, YE AZ, et al. Epidemiological and molecular virological characteristics of HBV infected patients of hospital with simultaneously positive HBsAg and anti-HBs[J]. Chin J Clin Lab Sci, 2017, 35 (1) :47-52. (in Chinese) 傅晓春, 陈静, 叶爱珠, 等.医院就诊人群HBsAg与抗HBs双阳性HBV感染者的流行病学与分子病毒学特征[J].临床检验杂志, 2017, 35 (1) :47-52.

[22] MOHER D, LIBERATI A, TETZLAFF J, et al. Preferred reporting items for systematic reviews and meta-analyses:The PRISMA statement[J]. PLo S Med, 2009, 6 (7) :e1000097.

[23] Prevention of Infection Related Cancer (PIRCA) Group, Specialized Committee of Cancer Prevention and Control, Chinese Preventive Medicine Association; Non-communicable&Chronic Disease Control and Prevention Society, Chinese Preventive Medicine Association; Health Communication Society, Chinese Preventive Medicine Association. Strategies of primary prevention of liver cancer in China:Expert consensus (2018) [J]. J Clin Hepatol, 2018, 34 (10) :2090-2097. (in Chinese) 中华预防医学会肿瘤预防与控制专业委员会感染相关肿瘤防控学组, 中华预防医学会慢病预防与控制分会, 中华预防医学会健康传播分会.中国肝癌一级预防专家共识 (2018) [J].临床肝胆病杂志, 2018, 34 (10) :2090-2097.

[24] YU DM, LI XH, MOM V, et al. N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape[J]. J Hepatol, 2014, 60 (3) :515-522.

[25] DING F, MIAO XL, LI YX, et al. Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and antiHBs[J]. Braz J Infect Dis, 2016, 20 (1) :1-7.

[26] LIU W, CAO Y, WANG T, et al. The N-glycosylation modification of LHBs (large surface proteins of HBV) effects on endoplasmic reticulum stress, cell proliferation and its secretion[J]. Hepat Mon, 2013, 13 (9) :e12280.

[27] WEINBERGER KM, ZOULEK G, BAUER T, et al. A novel deletion mutant of hepatitis B virus surface antigen[J]. J Med Virol, 1999, 58 (2) :105-110.

[28] CHEN CJ, YANG HI, SU J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level[J]. JAMA, 2006, 295 (1) :65-73.

[29] CHEN CH, HUNG CH, LEE CM, et al. Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBe Ag-negative patients[J]. Gastroenterology, 2007, 133 (5) :1466-1474.

[30] HSIEH YH, SU IJ, WANG HC, et al. Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage[J]. Carcinogenesis, 2004, 25 (10) :2023-2032.

[31] WANG HC, HUANG W, LAI MD, et al. Hepatitis B virus preS mutants, endoplasmic reticulum stress and hepatocarcinogenesis[J]. Cancer Sci, 2006, 97 (8) :683-688.

[32] CHEN Y, QIAN F, YUAN Q, et al. Mutations in hepatitis B virus DNA from patients with coexisting HBsAg and anti-HBs[J]. J Clin Virol, 2011, 52 (3) :198-203.

[33] KAO JH, CHEN PJ, LAI MY, et al. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers[J]. Gastroenterology, 2003, 124 (2) :327-334.

[34] LIN CL, LIAO LY, WANG CS, et al. Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B[J]. Liver Int, 2005, 25 (3) :564-570.

[35] TONG MJ, BLATT LM, KAO JH, et al. Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen-positive hepatocellular carcinoma:A comparison with chronic carriers[J]. Liver Int, 2007, 27 (10) :1356-1363.

[36] ZHENG JX, ZENG Z, ZHENG YY, et al. Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients[J]. J Viral Hepat, 2011, 18 (10) :e423-e431.

[37] LEVRERO M, ZUCMAN-ROSSI J. Mechanisms of HBV-induced hepatocellular carcinoma[J]. J Hepatol, 2016, 64 (1Suppl) :s84-s101.

施引文献

期刊类型引用(30)

1.	汪淑佳，俞黎. 多学科团队诊疗模式下的PDCA循环管理在梗阻性黄疸患者围术期护理中的应用效果分析. 中国社区医师. 2025(02): 96-98 . 百度学术
2.	易衡，何芬，王曦，冯谦，唐杰，卿小琼，孙菲菲，陈重. 超声引导下PTCD治疗晚期MOJ疗效及预后因素分析. 武汉大学学报(医学版). 2024(07): 814-819 . 百度学术
3.	李鸿. 老年晚期恶性梗阻性黄疸患者实时超声弹性成像定量分析对PTCD预后的预测价值. 昆明医科大学学报. 2023(01): 122-127 . 百度学术
4.	李鸿. 老年晚期恶性梗阻性黄疸患者实时超声弹性成像定量分析对PTCD预后的评估价值. 昆明医科大学学报. 2023(02): 150-155 . 百度学术
5.	梁亚丽，李馨，夏俊杰. 胰腺癌梗阻性黄疸患者经皮穿刺胆管引流术后发生胰腺炎的危险因素分析. 实用癌症杂志. 2023(08): 1321-1324 . 百度学术
6.	杨立新，刘茜，周晶晶，唐亚丹，傅鹏，戴峰，白淑芬. 不同方法PTCD应用于梗阻性黄疸治疗中的体会. 现代医用影像学. 2023(12): 2229-2231+2235 . 百度学术
7.	华建军. 超声引导下经皮肝穿刺胆管引流术治疗对阻塞性黄疸病人胆红素水平与肝功能的影响研究. 贵州医药. 2022(02): 226-227 . 百度学术
8.	黄道琼，沈小叶，刘骏，刘月娥，陈瑜. 回授法在经皮肝穿刺胆管引流术后的应用. 介入放射学杂志. 2022(03): 294-297 . 百度学术
9.	彭赵宏，张德志，施万印，赵本胜，熊壮，汪名权，宋文，陶龙香，刘斌，张帅，程翔. ~(125)I粒子支架治疗恶性梗阻性黄疸支架通畅时间的影响因素分析. 安徽医科大学学报. 2022(04): 645-649 . 百度学术
10.	王玮，陈熙，罗丹，李启祥，尹合坤. 不同姑息性引流术对低位恶性梗阻性黄疸的近远期疗效及安全性分析. 当代医学. 2022(19): 39-42 . 百度学术
11.	买买提·瓦司力，高旭升，司俊杰，徐峰. 经皮肝穿引流和支架植入在恶性梗阻性黄疸患者治疗的疗效评价. 新疆医学. 2022(07): 770-772+809 . 百度学术
12.	王颖. 彩超引导经皮穿刺肝胆管引流术治疗梗阻性黄疸的临床研究. 中国医疗器械信息. 2022(15): 123-125 . 百度学术
13.	宋飞，向盈盈，车佳音，李红阳，徐文勇，魏凌潇，黄明. 胆道~(125)I粒子支架与金属裸支架治疗Bismuth Corlette Ⅲ型胆管癌合并梗阻性黄疸的临床对比. 昆明医科大学学报. 2022(11): 85-89 . 百度学术
14.	冉庆. ERCP联合PTCD胆总管支架置入胆管引流治疗恶性梗阻性黄疸的临床价值. 医学食疗与健康. 2021(04): 86-87 . 百度学术
15.	王锦程，余佩和，苏松，李波. 经内镜鼻胆管引流术与经内镜胆道支架置入术在低位恶性梗阻性黄疸术前胆道引流效果比较的Meta分析. 临床肝胆病杂志. 2021(04): 863-867 . 本站查看
16.	马博，周军，周京涛，李建刚，王俊. 胆道支架植入治疗恶性梗阻性黄疸术后并发症的发生因素分析. 现代生物医学进展. 2021(07): 1283-1286 . 百度学术
17.	张建松，侯森，崔虎啸. 超声引导下经皮肝穿刺胆道引流联合胆管复合支架置入术治疗晚期肝外胆管癌的效果. 癌症进展. 2021(09): 931-934 . 百度学术
18.	张华安，周晓芳，蒋易君，张淏嘉. NRS-2002联合炎症反应标志物预测恶性梗阻性黄疸患者预后的Nomogram模型构建. 山东医药. 2021(16): 35-40 . 百度学术
19.	石书伟，王劲. 经皮肝穿刺胆道引流联合金属支架植入术对恶性梗阻性黄疸的影响. 黑龙江医学. 2021(15): 1608-1609 . 百度学术
20.	宋英茜，陶冶. 梗阻性黄疸经皮肝穿刺胆道引流术后胆道感染的病原菌特点及其危险因素分析. 中国实用乡村医生杂志. 2021(02): 33-36 . 百度学术
21.	张志强，韩涛，崔钢，王奕，蔡恒烈，廖骞. 右肝管入路单通道横跨左右肝管引流治疗汇管区恶性梗阻性黄疸的临床研究. 中国普通外科杂志. 2021(12): 1503-1508 . 百度学术
22.	傅建英. 内镜介入治疗急性梗阻性黄疸的疗效及对患者炎症因子的影响. 中外医疗. 2021(33): 57-60 . 百度学术
23.	李蔚，王锡斌，崔卫东，杨青，刘会苗，杨金雨，王锡斌. 超声引导下经皮经肝胆管穿刺引流术治疗急性梗阻性化脓性胆管炎患者疗效分析. 实用肝脏病杂志. 2020(03): 447-450 . 百度学术
24.	李磊. 胆道支架联合经皮肝穿刺胆管引流术对晚期恶性梗阻性黄疸的临床应用价值. 名医. 2020(08): 85-86 . 百度学术
25.	张蓓，答秀维，张乐. 经皮肝穿刺胆道外引流治疗恶性梗阻性黄疸疗效及对患者细胞免疫功能、血清直接胆红素、超敏C反应蛋白水平的影响. 陕西医学杂志. 2020(10): 1249-1252 . 百度学术
26.	朱超，刘会春，胡小四，庞青，陈邦邦，李传涛. 胆道双支架联合~(125)I粒子腔内照射治疗恶性肝门部胆道梗阻的疗效分析. 介入放射学杂志. 2020(11): 1100-1104 . 百度学术
27.	姜磊，都晓英，孙医学，张大坤，周凯，徐建中，陈芳芳. PTBS术治疗恶性梗阻性黄疸的临床价值及预后因素分析. 蚌埠医学院学报. 2019(09): 1202-1205+1209 . 百度学术
28.	江新华. 64层螺旋CT3D成像与MRCP成像技术对胆道梗阻性疾病的诊断价值. 江西医药. 2019(11): 1336-1340 . 百度学术
29.	吴子鑫，吴申伟. 经皮肝穿刺胆道支架植入治疗对恶性梗阻性黄疸患者肝功能指标、炎症指标的影响. 齐齐哈尔医学院学报. 2019(24): 3098-3099 . 百度学术
30.	武飞. 经皮肝穿刺胆管引流术与Roux-en-Y胆肠吻合术治疗恶性梗阻性黄疸患者的对比研究. 中国药物与临床. 2019(23): 4098-4100 . 百度学术