ALT正常肝组织学轻度异常的慢性乙型肝炎患者经恩替卡韦抗病毒治疗的效果分析

刘志红; 江建宁; 苏明华; 李仕华; 胡伯斌; 付嘉鑫; 傅燕平; 李慧娇; 郭莉

doi:10.3969/j.issn.1001-5256.2021.08.009

ALT正常肝组织学轻度异常的慢性乙型肝炎患者经恩替卡韦抗病毒治疗的效果分析

DOI: 10.3969/j.issn.1001-5256.2021.08.009

广西医科大学第一附属医院感染性疾病科，广西艾滋病防治研究重点实验室，南宁 530021

基金项目:

国家“十三五”艾滋病和病毒性肝炎等重大传染病防治科技重大专项 (2017ZX10202201)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：刘志红、江建宁负责课题设计，资料分析，撰写论文；刘志红、李仕华、胡伯斌、付嘉鑫参与收集数据，修改论文；江建宁、苏明华负责拟定写作思路，指导撰写文章并最后定稿；傅燕平、李慧娇、郭莉参与收集和分析数据。

详细信息

通信作者:
江建宁，jjianning@163.com

中图分类号: R512.62
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出版历程
- 收稿日期: 2020-12-16
- 录用日期: 2021-02-01
- 出版日期: 2021-08-20

Clinical effect of entecavir antiviral therapy in chronic hepatitis B patients with persistently normal alanine aminotransferase and mild liver histological abnormalities

Guangxi Key Laboratory of AIDS Prevention and Treatment, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

Research funding:

National "Thirteenth Five-Year Plan" AIDS and Viral Hepatitis and Other Major Infectious Diseases Prevention and Control Technology Major Special Projects (2017ZX10202201)

摘要

摘要: 目的对ALT正常肝组织学轻度异常的慢性乙型肝炎患者给予恩替卡韦治疗，探讨其抗病毒治疗的可行性。方法回顾性纳入2008年1月—2018年1月广西医科大学第一附属医院收治的HBV感染者181例。入组患者中基线ALT正常者归入研究组(n=61)，基线ALT 1~2×ULN归入对照1组(n=62)，基线ALT＞2×ULN归入对照2组(n=58)，经恩替卡韦抗病毒治疗至少1年，对比3组间临床疗效。采用寿命表法计算病毒学应答、HBeAg血清学应答和病毒学突破的累积进展率以及年发生率。计量资料多组间比较采用单因素方差分析，两两比较采用SNK法；计数资料多组间比较采用χ²检验。结果 181例中男性124例(68.5%)，HBeAg阳性80例(44.2%)，平均随访时间3.63年。3组病毒学应答年均发生率分别为74.37%、71.89%、74.21%(χ²=2.91，P=0.371)，3组病毒学突破年发生率分别为3.48%、5.17%、2.73%(χ²=1.72，P=0.097)。3组HBeAg阳性患者年均阴转率分别为9.79%、37.16%、38.24%(χ²=1.37，P=0.01)，3组HBeAg年均转换率分别为9.10%、31.35%、36.74%(χ²=5.61，P=0.021)，研究组HBeAg年均阴转率及HBeAg年均转换率均低于对照1组和2组(P值均＜0.05)。结论 ALT正常的HBV感染者经恩替卡韦抗病毒治疗可以获得理想的病毒学应答，但免疫学应答有待提高。
- 乙型肝炎, 慢性 /
- 抗病毒药 /
- 治疗结果
Abstract: Objective To investigate the clinical effect of entecavir antiviral therapy in chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT) and mild liver histological abnormalities. Methods A retrospective analysis was performed for 181 patients with hepatitis B virus (HBV) infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from January 2008 to January 2018, and according to the baseline ALT level, they were divided into study group (61 patients with PNALT at baseline), control group 1 [62 patients with an ALT level of (1-2)×upper limit of normal (ULN)], and control group 2 (58 patients with an ALT level of > 2×ULN). Entecavir antiviral therapy was given for at least 1 year, and clinical outcome was compared between the three groups. The life-table method was used to calculate the cumulative progression rates and annual incidence rates of virologic response, HBeAg serological response, and virologic breakthrough. An analysis of variance was used for comparison of continuous data between groups, and the SNK method was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Among the 181 patients enrolled in this study, there were 124 male patients (68.5%) and 80 patients with positive HBeAg (44.2%), with a mean follow-up time of 3.63 years. The three groups had a mean annual incidence rate of virologic response of 74.37%, 71.89%, and 74.21%, respectively (χ²=2.91, P=0.371) and an annual incidence rate of virologic breakthrough of 3.48%, 5.17%, and 2.73%, respectively (χ²=1.72, P=0.097). For the patients with positive HBeAg, the three groups had a mean annual clearance rate of 9.79%, 37.16%, and 38.24%, respectively (χ²=1.37, P=0.01) and a mean annual HBeAg seroconversion rate of 9.10%, 31.35%, and 36.74%, respectively (χ²=5.61, P=0.021); the study group had significantly lower mean annual clearance rate and seroconversion rate of HBeAg than the control groups 1 and 2 (all P < 0.05). Conclusion CHB patients with PNALT level can obtain satisfactory virologic response after entecavir antiviral therapy, while immunological response needs to be further improved.
- Hepatitis B, Chronic /
- Antiviral Agents /
- Treatment Outcome

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表 1 研究对象人口学和基线临床特征

指标	研究组(n=61)	对照1组(n=62)	对照2组(n=58)	统计值	P值
年龄(岁)	55.60±3.50	42.30±3.92	40.50±5.72	F=1.91	0.043
男/女(例)	41/20	43/19	40/18	χ²=2.12	0.623
HBeAg阳性/阴性(例)	20/41	30/32	30/28	χ²=1.32	0.032
基线ALT(U/L)	26.57±6.31	60.41±11.65	157.61±32.69	F=1.90	0.017
HBV DNA(log₁₀)	4.82±1.60	5.69±1.43	6.17±1.83	F=1.87	0.218
随访时间(年)	3.28±1.59	3.06±2.51	3.75±1.73	F=0.38	0.273

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表 2 病毒学应答累积发生率

组别	例数	转阴例数	随访人年	累积应答率(%)			年均应答率 (%)
组别	例数	转阴例数	随访人年	3个月	6个月	9个月	年均应答率 (%)
研究组	61	61	113	65	96	100	74.37
对照1组	62	62	125	64	92	99	71.89
对照2组	58	58	107	70	89	99	74.21

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表 3 HBeAg累积阴转率

组别	例数	转阴例数	随访人年	累积阴转率(%)			年均阴转率 (%)
组别	例数	转阴例数	随访人年	1年	2年	3年	年均阴转率 (%)
研究组	20	3	31.7	10	18	20	9.79
对照1组	30	17	64.8	31	58	65	37.16¹⁾
对照2组	30	18	65.6	37	61	64	38.24¹⁾
注：3组间年均阴转率比较，χ²=1.37, P=0.01;与研究组比较，1)P＜0.05。

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表 4 HBeAg累积转换率

组别	>例数	>转换例数	>随访人年	累积转换率(%)			>年均转换率 (%)
组别	>例数	>转换例数	>随访人年	1年	2年	3年	>年均转换率 (%)
研究组	20	3	37.5	10	20	20	9.10
对照1组	30	13	57.6	29	47	60	31.35¹⁾
对照2组	30	15	56.3	40	58	61	36.74¹⁾
注：3组间年均转换率比较，χ²=5.61，P=0.021；与研究组比较，1)P＜0.05。

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表 5 病毒学突破累积发生率

组别	例数	病毒学突破例数	随访人年	累积突破率(%)			年均突破率 (%)
组别	例数	病毒学突破例数	随访人年	1年	2年	3年	年均突破率 (%)
研究组	61	4	139	4	8	8	3.48
对照1组	62	9	181	2	15	17	5.17
对照2组	58	3	185	2	4	6	2.73
注：3组间年均突破率比较，χ²=1.72, P=0.097。

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