慢性乙型肝炎患者HBeAg血清学转换影响因素的研究进展

顾子杨; 王安辉; 何文昌; 李佳玉; 黄长形

doi:10.3969/j.issn.1001-5256.2022.11.029

慢性乙型肝炎患者HBeAg血清学转换影响因素的研究进展

DOI: 10.3969/j.issn.1001-5256.2022.11.029

1.
空军军医大学第二附属医院传染病科，西安 710038
2.
空军军医大学军事预防医学系流行病学教研室，西安 710032

基金项目:

国家自然科学基金面上项目 (81872670)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：顾子杨负责撰写论文；何文昌、李佳玉负责文献搜集及分析；王安辉负责修改论文；黄长形负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
黄长形，13572133011@163.com

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出版历程
- 收稿日期: 2022-04-30
- 录用日期: 2022-06-14
- 出版日期: 2022-11-20

Influencing factors for HBeAg seroconversion in patients with chronic hepatitis B

1.
Department of Infectious Diseases, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China
2.
Department of Epidemiology, School of Military Preventive Medicine, Air Force Medical University, Xi'an 710032, China

Research funding:

General Program of National Natural Science Foundation of China (81872670)

More Information

Corresponding author: HUANG Changxing, 13572133011@163.com(ORCID: 0000-0001-5511-2999)

摘要

摘要: HBeAg血清学转换是指既往HBeAg阳性的慢性乙型肝炎(CHB)患者HBeAg消失，抗-HBe出现。HBeAg血清学转换标志着病毒复制降低、免疫耐受减弱和肝脏炎症减轻，是评估病情和评价CHB抗病毒治疗效果的重要监测指标，预示着治疗满意的终点。探索影响HBeAg血清学转换的不同因素，对CHB患者治疗方案的选择以及预后评估意义重大。本综述主要就HBV病毒学因素、宿主遗传因素、药物因素、免疫学因素等方面与CHB患者发生HBeAg血清学转换的关系展开阐述。
- 乙型肝炎, 慢性 /
- 乙型肝炎e抗原 /
- 影响因素
Abstract: HBeAg seroconversion refers to the disappearance of HBeAg and the appearance of anti-HBe in chronic hepatitis B (CHB) patients with positive HBeAg in the past. HBeAg seroconversion marks the reductions in viral replication, immune tolerance, and liver inflammation and is an important monitoring indicator for evaluating disease conditions and the effect of CHB antiviral therapy, and it also indicates the endpoint of satisfactory treatment. Exploring the influencing factors for HBeAg seroconversion is of great significance to the selection of treatment regimens and the prognostic evaluation of CHB patients. This article mainly elaborates on the association of HBV with HBeAg seroconversion in CHB patients from the aspects of virological factors, host genetic factors, drug factors, and immunological factors.
- Hepatitis B, Chronic /
- Hepatitis B e Antigens /
- Influencing Factors

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参考文献(44)

[1]	Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[2]	CHEN Q, ZHANG J, HUANG J, et al. Early serum HBsAg drop is a strong predictor of HBeAg seroconversion and HBsAg loss to pegylated interferon alfa-2a in chronic hepatitis B patients with prior nucleos(t)ide analogue exposure[J]. Med Sci Monit, 2019, 25: 4665-4674. DOI: 10.12659/MSM.916441.
[3]	LIN TC, CHIU YC, CHIU HC, et al. Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy[J]. World J Gastroenterol, 2018, 24(6): 725-736. DOI: 10.3748/wjg.v24.i6.725.
[4]	ZHAO XA, WANG J, LIU J, et al. Baseline serum hepatitis B core antibody level predicts HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B after antiviral treatment[J]. Antiviral Res, 2021, 193: 105146. DOI: 10.1016/j.antiviral.2021.105146.
[5]	CAI S, LI Z, YU T, et al. Serum hepatitis B core antibody levels predict HBeAg seroconversion in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analogs[J]. Infect Drug Resist, 2018, 11: 469-477. DOI: 10.2147/IDR.S163038.
[6]	CHEN HS, WU JF, SU TH, et al. Baseline level of hepatitis B core antibody predicts spontaneous hepatitis B e Antigen (HBeAg) seroconversion in HBeAg-positive children with a normal alanine aminotransferase level[J]. Hepatology, 2019, 70(6): 1903-1912. DOI: 10.1002/hep.30788.
[7]	CHI XM, WANG XM, WANG ZF, et al. Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B[J]. World J Gastroenterol, 2021, 27(40): 6927-6938. DOI: 10.3748/wjg.v27.i40.6927.
[8]	SONNEVELD MJ, van OORD GW, van CAMPENHOUT MJ, et al. Relationship between hepatitis B core-related antigen levels and sustained HBeAg seroconversion in patients treated with nucleo(s)tide analogues[J]. J Viral Hepat, 2019, 26(7): 828-834. DOI: 10.1111/jvh.13097.
[9]	LEE HA, LEE HW, PARK Y, et al. Hepatitis B core-related antigen is useful for predicting phase and prognosis of hepatitis B e antigen-positive patients[J]. J Clin Med, 2022, 11(6): 1729. DOI: 10.3390/jcm11061729.
[10]	LEE WM, KING WC, JANSSEN H, et al. Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: A prospective cohort study[J]. J Viral Hepat, 2021, 28(11): 1526-1538. DOI: 10.1111/jvh.13591.
[11]	HUANG YJ, CHANG CS, PENG YC, et al. On-treatment HBV DNA level could predict HBeAg seroclearance in patients with HBeAg-positive chronic hepatitis B with entecavir therapy[J]. J Chin Med Assoc, 2017, 80(6): 341-346. DOI: 10.1016/j.jcma.2016.12.005.
[12]	FU XY, TAN DM, LIU CM, et al. Early hepatitis B viral DNA clearance predicts treatment response at week 96[J]. World J Gastroenterol, 2017, 23(16): 2978-2986. DOI: 10.3748/wjg.v23.i16.2978.
[13]	WANG X, WANG Z, CHI X, et al. Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks[J]. Int J Infect Dis, 2020, 99: 171-178. DOI: 10.1016/j.ijid.2020.07.031.
[14]	WANG Y, LIAO H, DENG Z, et al. Serum HBV RNA predicts HBeAg clearance and seroconversion in patients with chronic hepatitis B treated with nucleos(t)ide analogues[J]. J Viral Hepat, 2022, 29(6): 420-431. DOI: 10.1111/jvh.13671.
[15]	JIA W, ZHU MQ, QI X, et al. Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a[J]. Virol J, 2019, 16(1): 61. DOI: 10.1186/s12985-019-1152-6.
[16]	LUO H, TAN N, KANG Q, et al. Hepatitis B virus pregenomic RNA status can reveal the long-term prognoses of chronic hepatitis B patients treated with nucleos(t)ide analogues[J]. J Viral Hepat, 2020, 27(3): 323-328. DOI: 10.1111/jvh.13227.
[17]	WU Y, WEN J, TANG G, et al. On-treatment HBV RNA dynamic predicts entecavir-induced HBeAg seroconversion in children with chronic hepatitis B[J]. J Infect, 2021, 83(5): 594-600. DOI: 10.1016/j.jinf.2021.08.044.
[18]	CHEN CH, LEE CM, HUNG CH, et al. Hepatitis B virus genotype B results in better immediate, late and sustained responses to peginterferon-alfa in hepatitis-B-e-antigen-positive patients[J]. J Gastroenterol Hepatol, 2011, 26(3): 461-468. DOI: 10.1111/j.1440-1746.2010.06429.x.
[19]	LAU D, GANOVA-RAEVA L, WANG J, et al. Precore and basal core promoter hepatitis B virus (HBV) variants are present from a young age and differ across HBV genotypes[J]. Hepatology, 2021, 73(5): 1637-1651. DOI: 10.1002/hep.31506.
[20]	LUO Y, PAN M, NING M, et al. High mutation prevalence of precore and basal core promoter in pregnant women who underwent spontaneous HBeAg seroconversion within one year postpartum[J]. Dig Liver Dis, 2020, 52(2): 199-204. DOI: 10.1016/j.dld.2019.06.021.
[21]	LIU WC, WU IC, CHIU YC, et al. Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients[J]. Antiviral Res, 2020, 176: 104719. DOI: 10.1016/j.antiviral.2020.104719.
[22]	LI T, LIU F, ZHANG L, et al. Host genetic factors in predicting response status in chronic hepatitis B patients discontinuing nucleos(t)ide analogs[J]. Saudi J Gastroenterol, 2018, 24(1): 30-36. DOI: 10.4103/sjg.SJG_228_17.
[23]	WANG H, WU H, BAO S, et al. Association of IPS1 polymorphisms with peginterferon efficacy in chronic hepatitis B with HBeAg-positive in the Chinese population[J]. Infect Genet Evol, 2015, 31: 161-168. DOI: 10.1016/j.meegid.2015.01.013.
[24]	RYBICKA M, WOZIWODZKA A, ROMANOWSKI T, et al. Host genetic background affects the course of infection and treatment response in patients with chronic hepatitis B[J]. J Clin Virol, 2019, 120: 1-5. DOI: 10.1016/j.jcv.2019.09.002.
[25]	THANAPIROM K, SUKSAWATAMNUAY S, SUKEEPAISARNJAREON W, et al. Genetic variation in the vitamin D pathway CYP2R1 gene predicts sustained HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon: A multicenter study[J]. PLoS One, 2017, 12(3): e0173263. DOI: 10.1371/journal.pone.0173263.
[26]	TAI J, LIU F, WANG Y, et al. Efficacy of acupuncture combined with Shuimu Liangzi Decoction in treating the syndrome of liver and kidney yin deficiency in patients with chronic hepatitis B and its effect on intestinal flora[J]. J Changchun Univ Chin Med, 2021, 37(1): 115-118. DOI: 10.13463/j.cnki.cczyy.2021.01.031. 台杰, 刘峰, 王燕, 等. 针刺联合加味水木两滋汤治疗慢性乙型肝炎肝肾阴虚证疗效及对肠道菌群的影响[J]. 长春中医药大学学报, 2021, 37(1): 115-118. DOI: 10.13463/j.cnki.cczyy.2021.01.031.
[27]	CON D, GOODWIN T, MAJEED A, et al. Comparison of 48-week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta-analysis[J]. J Viral Hepat, 2021, 28(1): 40-50. DOI: 10.1111/jvh.13400.
[28]	CHEN L, LIN L, ZHOU H, et al. Peginterferon and entecavir combination therapy improves outcome of non-early response hepatitis B e antigen-positive patients[J]. Open Forum Infect Dis, 2020, 7(11): ofaa462. DOI: 10.1093/ofid/ofaa462.
[29]	LI J, QU L, SUN X, et al. Peg-interferon alpha add-on Tenofovir disoproxil fumarate achieved more HBsAg loss in HBeAg-positive chronic hepatitis B naïve patients[J]. J Viral Hepat, 2021, 28(10): 1381-1391. DOI: 10.1111/jvh.13571.
[30]	LI X, ZHOU D, CHI X, et al. Entecavir combining Chinese herbal medicine for HBeAg-positive chronic hepatitis B patients: a randomized, controlled trial[J]. Hepatol Int, 2020, 14(6): 985-996. DOI: 10.1007/s12072-020-10097-z.
[31]	SHI WJ, ZHANG Y, WANG ZX, et al. Correlation between liver pathological features and laboratory parameters of 91 patients of chronic hepatitis B with alanine aminortransferase lower than 2×upper limits of normal[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2020, 14(2): 138-143. DOI: 10.3877/cma.j.issn.1674-1358.2020.02.010. 施文娟, 张妍, 王兆勋, 等. 91例丙氨酸氨基转移酶低于正常值上限二倍的慢性乙型肝炎患者肝组织病理特征与实验室指标的相关性[J/CD]. 中华实验和临床感染病杂志(电子版), 2020, 14(2): 138-143. DOI: 10.3877/cma.j.issn.1674-1358.2020.02.010.
[32]	WANG CH, CHANG KK, LIN RC, et al. Consolidation period of 18 months no better at promoting off-treatment durability in HBeAg- positive chronic hepatitis B patients with tenofovir disoproxil fumarate treatment than a 12-month period: A prospective randomized cohort study[J]. Medicine (Baltimore), 2020, 99(18): e19907. DOI: 10.1097/MD.0000000000019907.
[33]	BRAHMANIA M, LOMBARDERO M, HANSEN BE, et al. Association between severe serum alanine aminotransferase flares and hepatitis B e antigen seroconversion and HBV DNA decrease in untreated patients with chronic HBV infection[J]. Clin Gastroenterol Hepatol, 2019, 17(12): 2541-2551. e2. DOI: 10.1016/j.cgh.2019.02.005.
[34]	CHEN T, ZHU L, SHI A, et al. Functional restoration of CD56bright NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B[J]. Hepatol Int, 2017, 11(5): 419-428. DOI: 10.1007/s12072-017-9803-4.
[35]	HUANG F, LU MH, GONG HY, et al. Changes in peripheral blood natural killer T cells in hepatitis B e antigen-positive chronic hepatitis B patients and efficacy prediction after pegylated interferon therapy[J]. Genet Mol Res, 2015, 14(2): 4932-4938. DOI: 10.4238/2015.May.11.26.
[36]	LIN C, ZOU H, WANG S. Hepatitis B e antigen seroconversion is related with the function of dendritic cells in chronic hepatitis B virus infection[J]. Gastroenterol Res Pract, 2014, 2014: 413952. DOI: 10.1155/2014/413952.
[37]	WEI MJ, PAN XN, WEI KP, et al. Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection[J]. Int Immunopharmacol, 2015, 27(2): 238-243. DOI: 10.1016/j.intimp.2015.06.019.
[38]	CHOI YH, LEE HW, PURDY MA. Natural antibody IgG levels are associated with HBeAg-positivity and seroconversion in chronic hepatitis B patients treated with entecavir[J]. Sci Rep, 2022, 12(1): 4382. DOI: 10.1038/s41598-022-08457-w.
[39]	KHLAIPHUENGSIN A, CHUAYPEN N, HIRANKARN N, et al. Circulating BAFF and CXCL10 levels predict response to pegylated interferon in patients with HBeAg-positive chronic hepatitis B[J]. Asian Pac J Allergy Immunol, 2021, 39(2): 129-135. DOI: 10.12932/AP-050718-0365.
[40]	YANG J, SHENG G, XIAO D, et al. The frequency and skewed T-cell receptor beta-chain variable patterns of peripheral CD4(+)CD25(+) regulatory T-cells are associated with hepatitis B e antigen seroconversion of chronic hepatitis B patients during antiviral treatment[J]. Cell Mol Immunol, 2016, 13(5): 678-687. DOI: 10.1038/cmi.2015.100.
[41]	XIA J, HUANG R, CHEN Y, et al. Profiles of serum soluble programmed death-1 and programmed death-ligand 1 levels in chronic hepatitis B virus-infected patients with different disease phases and after anti-viral treatment[J]. Aliment Pharmacol Ther, 2020, 51(11): 1180-1187. DOI: 10.1111/apt.15732.
[42]	LU YQ, WU J, WU XJ, et al. Interferon gamma-inducible protein 16 of peripheral blood mononuclear cells may sense hepatitis B virus infection and regulate the antiviral immunity[J]. Front Cell Infect Microbiol, 2021, 11: 790036. DOI: 10.3389/fcimb.2021.790036.
[43]	TSAI TY, PENG CY, YANG HI, et al. The human C-type lectin 18 is a potential biomarker in patients with chronic hepatitis B virus infection[J]. J Biomed Sci, 2018, 25(1): 59. DOI: 10.1186/s12929-018-0460-2.
[44]	XIA Z, ZHENG J, ZHENG L, et al. Effects of dyslipidemia on E antigen seroconversion of patients with chronic hepatitis B treated by nucleoside (acid) analogs[J]. Lipids Health Dis, 2021, 20(1): 148. DOI: 10.1186/s12944-021-01582-x.