HBeAg阴性慢性HBV感染期患者的临床治愈及影响因素

摘要/Abstract

摘要： HBeAg阴性慢性HBV感染期,又称免疫控制期,该期患者多无临床症状且未接受抗病毒治疗,但病程中仅少部分患者能发生HBsAg血清学转换。多项研究发现,该期患者接受抗病毒治疗尤其是干扰素治疗后获得临床治愈的概率高于其他期患者。本文通过整理HBeAg阴性慢性HBV感染期患者抗病毒治疗相关临床研究数据,对免疫控制期患者是否需要治疗、治疗方案的差异、临床治愈的可能性及影响因素进行综述。

谢艳迪, 张昕怡, 封波. HBeAg阴性慢性HBV感染期患者的临床治愈及影响因素[J]. 肝脏, 2024, 29(6): 631-634.

/ 推荐

[1] 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(2022年版)[J]. 中华传染病杂志, 2023, 41(1):3-28.
[2] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-98.
[3] 周路路, 刘娜, 李春霞, 等. 慢性HBV感染免疫控制期的抗病毒治疗[J]. 临床肝胆病杂志, 2020, 36(5):1134-7.
[4] Terrault N A, Lok A S F, McMahon B J, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4): 1560-99.
[5] Sarin S K, Kumar M, Lau G K, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update[J]. Hepatol Int, 2016, 10(1): 1-98.
[6] 白萧萧, 东冰, 徐光华. 慢性HBV感染免疫控制期与免疫逃逸期研究进展[J]. 肝脏, 2018, 23(4):344-7.
[7] Wang H, Luo H, Wan X, et al. TNF-α/IFN-γ profile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection[J]. J Hepatol, 2020, 72(1): 45-56.
[8] Habersetzer F, Moenne-Loccoz R, Meyer N, et al. Loss of hepatitis B surface antigen in a real-life clinical cohort of patients with chronic hepatitis B virus infection[J]. Liver Int, 2015, 35(1): 130-9.
[9] Invernizzi F, Viganò M, Grossi G, et al. The prognosis and management of inactive HBV carriers[J]. Liver Int, 2016, 36 Suppl 1: 100-4.
[10] WHO Guidelines Approved by the Guidelines Review Committee[M]. Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Geneva; World Health Organization, 2015.
[11] Papatheodoridis G V, Manolakopoulos S, Liaw Y F, Lok A. Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: a systematic review[J]. J Hepatol, 2012, 57(1): 196-202.
[12] 陈进, 卞冬雪, 叶卫江. 68例非活动性 HBsAg 携带者的肝组织病理及相关危险因素分析[J]. 浙江实用医学, 2013, (6):383-385.
[13] Zhai X, Zhu L, Jiang J, et al. Virological activity in treatment-naïve HBeAg-negative HBV-infected adult patients: A community-based study in Jiangsu, China[J]. Medicine (Baltimore), 2020, 99(29): e21179.
[14] 黄珊, 何清, 唐奇远, 等. 91例非活动性HBsAg携带者肝组织病理特点的研究[J]. 中国病毒病杂志, 2012, 2(01):58-61.
[15] Wu W J, Lin C L, Liu C J, et al. Lifetime risk of liver-related outcomes and determinants in male inactive carriers of chronic hepatitis B[J]. J Med Virol, 2023, 95(10): e29138.
[16] Kuang X J, Jia R R, Huo R R, et al. Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance[J]. J Viral Hepat, 2018, 25(9): 1026-37.
[17] Lin C L, Kao J H. Review article: the prevention of hepatitis B-related hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2018, 48(1): 5-14.
[18] Gaia S, Marzano A, Olivero A, et al. Inactive hepatitis B virus carriers: a favourable clinical condition[J]. Eur J Gastroenterol Hepatol, 2005, 17(12): 1435-1436.
[19] Indolfi G, Easterbrook P, Dusheiko G, et al. Hepatitis B virus infection in children and adolescents[J]. Lancet Gastroenterol Hepatol, 2019, 4(6): 466-476.
[20] Chien R N, Liaw Y F. Current Trend in Antiviral Therapy for Chronic Hepatitis B[J]. Viruses, 2022, 14(2):434.
[21] Hsu Y C, Yeh M L, Wong G L, et al. Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B[J]. J Infect Dis, 2021, 224(11): 1890-1899.
[22] Atay K, Hatemi İ, Canbakan B, et al. Five-year results of oral antiviral therapy in HBeAg-negative chronic Hepatitis B[J]. Turk J Gastroenterol, 2016, 27(3): 279-283.
[23] Fasano M, Lampertico P, Marzano A, et al. HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years[J]. J Hepatol, 2012, 56(6): 1254-1258.
[24] Jeng W J, Chen Y C, Chien R N, et al. Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B[J]. Hepatology, 2018, 68(2): 425-434.
[25] Lok A S, Zoulim F, Dusheiko G, Ghany M G. Hepatitis B cure: From discovery to regulatory approval[J]. J Hepatol, 2017, 67(4): 847-861.
[26] Islam M, Kumar K, Sevak J K, et al. Immune drivers of HBsAg loss in HBeAg-negative CHB patients after stopping nucleotide analog and administration of Peg-IFN[J]. Hepatol Commun, 2023, 7(5):e0098.
[27] Cao Z, Liu Y, Ma L, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66(4): 1058-1066.
[28] Marcellin P, Bonino F, Lau G K, et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a[J]. Gastroenterology, 2009, 136(7): 2169-79.e1-4.
[29] Su Q, Liu Y, Li J. Combined effect of pegylated interferon α with adefovir on renal function in Chinese patients with chronic hepatitis B[J]. Medicine (Baltimore), 2018, 97(34): e12089.
[30] Song A, Lin X, Lu J, et al. Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis[J]. Front Immunol, 2021, 12: 779347.
[31] Lim SG L G, Dan YY, et al. HBsAg loss in inactive chronic hepatitis B carriers is dependent on level of qHBsAg and interferon response: a randomized control trial[J]. AASLD2019, Abstracts (oral196).
[32] Li M H, Xie Y, Zhang L, et al. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a[J]. World J Hepatol, 2016, 8(15): 637-643.
[33] Zeng Q L, Yu Z J, Shang J, et al. Short-term Peginterferon-Induced High Functional Cure Rate in Inactive Chronic Hepatitis B Virus Carriers With Low Surface Antigen Levels[J]. Open Forum Infect Dis, 2020, 7(6): ofaa208.
[34] 李颍, 徐佳, 王延君, 丁芹. 回顾性分析聚乙二醇干扰素ɑ治疗慢性乙型肝炎HBsAg清除的预测因素分析[J]. 医学研究杂志, 2022, 51(4):109-113.
[35] Ouzan D, Pénaranda G, Joly H, et al. Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs[J]. J Clin Virol, 2013, 58(4): 713-717.
[36] Tangkijvanich P, Chittmittraprap S, Poovorawan K, et al. A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBeAg-negative chronic hepatitis B: Role of host and viral factors associated with treatment response[J]. J Viral Hepat, 2016, 23(6): 427-438.
[37] 李金伟. 聚乙二醇干扰素联合富马酸替诺福韦治疗HBeAg阴性慢性乙型肝炎的临床研究[J]. 世界复合医学, 2023, 9(3):164-166,170.
[38] Bahardoust M, Mokhtare M, Barati M, et al. A randomized controlled trial of pegylated interferon-alpha with tenofovir disoproxil fumarate for hepatitis B e antigen-negative chronic hepatitis B: A 48-week follow-up study[J]. J Infect Chemother, 2020, 26(12): 1265-1271.
[39] Li M H, Yi W, Zhang L, et al. Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy[J]. J Viral Hepat, 2019, 26 Suppl 1: 32-41.
[40] Zhang C, Yang Z, Wang Z, et al. HBV DNA and HBsAg: Early Prediction of Response to Peginterferon α-2a in HBeAg-Negative Chronic Hepatitis B[J]. Int J Med Sci, 2020, 17(3): 383-389.
[41] Farag M S, van Campenhout M J H, Pfefferkorn M, et al. Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B[J]. Clin Infect Dis, 2021, 72(2): 202-211.
[42] Jansen L, Kootstra N A, van Dort K A, et al. Hepatitis B Virus Pregenomic RNA Is Present in Virions in Plasma and Is Associated With a Response to Pegylated Interferon Alfa-2a and Nucleos(t)ide Analogues[J]. J Infect Dis, 2016, 213(2): 224-232.
[43] Limothai U, Chuaypen N, Poovorawan K, et al. Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon-based therapy in patients with hepatitis B e antigen-negative chronic hepatitis B[J]. J Viral Hepat, 2019, 26(12): 1481-1488.
[44] Yeo Y H, Ho H J, Yang H I, et al. Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis[J]. Gastroenterology, 2019, 156(3): 635-46.e9.
[45] Lai C L, Shouval D, Lok A S, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B[J]. N Engl J Med, 2006, 354(10): 1011-1020.
[46] Ye J, Chen J. Interferon and Hepatitis B: Current and Future Perspectives[J]. Front Immunol, 2021, 12: 733364.
[47] Wu Y, Liu Y, Lu J, et al. Durability of Interferon-induced Hepatitis B Surface Antigen Seroclearance[J]. Clin Gastroenterol Hepatol, 2020, 18(2): 514-6.e2.
[48] Song A, Wang X, Lu J, et al. Durability of hepatitis B surface antigen seroclearance and subsequent risk for hepatocellular carcinoma: A meta-analysis[J]. J Viral Hepat, 2021, 28(4): 601-612.

HBeAg阴性慢性HBV感染期患者的临床治愈及影响因素

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	孔维菊, 任传路, 周昱岐, 李竞争, 何清, 袁俊菲. 血清PIVKA-Ⅱ在HBV相关肝癌患者中的表达及其与肝功能的相关性[J]. 肝脏, 2024, 29(7): 794-797.
[2]	刘艳午, 田丹, 宋晶晶. 超声剪切波弹性成像结合血浆NRG4水平评估慢性乙型肝炎肝纤维化程度的价值[J]. 肝脏, 2024, 29(7): 825-829.
[3]	刘明, 郭艳, 陈文婷, 况雪梅, 李世炼, 揭丽, 夏杰, 毛青, 朱研. HBeAg阳性妊娠慢性HBV携带者母婴阻断停药后肝炎活动的危险因素研究[J]. 肝脏, 2024, 29(7): 834-839.
[4]	王雪梅, 宫富琪, 郑金娜, 于燕民, 徐菁, 杨永生. 重组人干扰素α-2b对丙型肝炎患者血清铁调素的影响及其机制[J]. 肝脏, 2024, 29(7): 840-843.
[5]	郝坤艳, 陈宇星, 汪文洋, 朱浩, 沈敏, 阳文新, 于乐成. 聚乙二醇干扰素对核苷(酸)类似物经治与未治的HBsAg低水平慢性乙型肝炎患者48周疗效比较[J]. 肝脏, 2024, 29(6): 635-640.
[6]	王春菊, 高嘉敏, 李丽容. 慢性乙型肝炎患者甲状腺激素水平与HBsAg水平及病情严重程度的相关性分析[J]. 肝脏, 2024, 29(6): 641-644.
[7]	宋舒瑛, 谢青, 姜绍文. 乙型肝炎治愈的临床研究进展[J]. 肝脏, 2024, 29(6): 725-730.
[8]	汪蕾, 陈晨, 华喜梅, 胡丰芬. 血清β-arrestin 2、HIF-1a及CA125联合预测慢性乙型肝炎肝纤维化的价值[J]. 肝脏, 2024, 29(5): 521-525.
[9]	李明慧, 王麟, 鲁凤民. 慢性乙型肝炎常见PC/BCP突变的可能致病机制[J]. 肝脏, 2024, 29(4): 371-373.
[10]	刘韵, 徐云, 韩亮, 钱艺, 谭碧波. 实时组织弹性成像评估慢性乙型肝炎患者食管静脉曲张的研究[J]. 肝脏, 2024, 29(4): 423-428.
[11]	蔡云, 赵凯, 潘良, 周鑫. IL-21参与HBeAg阳性慢性乙型肝炎的免疫发病机制的研究[J]. 肝脏, 2024, 29(4): 436-439.
[12]	余姣, 万谟彬. HBeAg阴性慢性乙型肝炎患者长期核苷(酸)类似物治疗停药后的随访及管理[J]. 肝脏, 2024, 29(3): 263-265.
[13]	程婉茜, 李茜, 杨大为. 经治慢性乙型肝炎低病毒血症患者序贯或联合富马酸丙酚替诺福韦的临床疗效及其影响因素[J]. 肝脏, 2024, 29(3): 289-292.
[14]	黎婉莹, 申笙, 刘诗, 孙剑. 血清HBV RNA在临床应用中尚未解决的关键科学问题[J]. 肝脏, 2024, 29(2): 143-146.
[15]	赵雅琳, 申川, 魏梦平, 赵彩彦. 不同抗病毒治疗方案对慢性丙型肝炎持续应答患者肝细胞癌发生的影响[J]. 肝脏, 2024, 29(2): 182-188.