长期使用恩替卡韦对慢性乙型肝炎患者肾小管功能的影响

车媛梅; 李嫒; 王亮; 张伦理; 李小鹏

doi:10.3969/j.issn.1001-5256.2023.06.010

长期使用恩替卡韦对慢性乙型肝炎患者肾小管功能的影响

DOI: 10.3969/j.issn.1001-5256.2023.06.010

车媛梅^{1, 2},
李嫒^{1, 3},
王亮¹,
张伦理¹,
李小鹏^1, , ,

1.
南昌大学第一附属医院感染科，南昌 330006
2.
江西省人民医院感染科，南昌 330006
3.
赣州市人民医院输血科，江西赣州 341000

基金项目:

江西省科技厅计划项目 (20161BCD40015);

江西省科技厅计划项目 (20212BAG70022);

南昌大学教改课题 (NCUJGLX-2020-166-162)

伦理学声明：本研究方案经由南昌大学第一附属医院伦理委员会审批，批号：IIT2021019。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：车媛梅、李嫒、李小鹏负责课题设计，资料分析，撰写论文；李嫒、王亮参与收集数据，修改论文；李小鹏、张伦理负责拟定写作思路，指导撰写文章并最后定稿。车媛梅和李嫒同为第一作者。

详细信息

通信作者:
李小鹏，lixiaopeng823@163.com (ORCID: 0000-0003-3644-4976)

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出版历程
- 收稿日期: 2022-09-30
- 录用日期: 2023-02-03
- 出版日期: 2023-06-20

Influence of long-term use of entecavir on renal tubular function in patients with chronic hepatitis B

Yuanmei CHE^{1, 2},
Ai LI^{1, 3},
Liang WANG¹,
Lunli ZHANG¹,
Xiaopeng LI^{1
, ,
,}

1.
Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
2.
Department of Infectious Diseases, Jiangxi Provincial People's Hospital, Nanchang 330006, China
3.
Department of Blood Transfusion, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, China

Research funding:

Science and Technology Plan Project of Jiangxi Provincial (20161BCD40015);

Science and Technology Plan Project of Jiangxi Provincial (20212BAG70022);

Teaching Reform Project of Nanchang University (NCUJGLX-2020-166-162)

More Information

Corresponding author: LI Xiaopeng, lixiaopeng823@163.com (ORCID: 0000-0003-3644-4976)

摘要

摘要: 目的分析长期使用恩替卡韦抗病毒治疗对慢性乙型肝炎(CHB)患者肾功能的可能影响，探索早期判断肾损伤的敏感指标。方法纳入2021—2022年南昌大学第一附属医院感染科门诊就诊的CHB患者，对125例恩替卡韦治疗1年以上的CHB患者(治疗组)和44例未进行抗病毒治疗的慢性HBV感染者(对照组)的血肌酐、肾小球滤过率(eGFR)以及尿α1微球蛋白(α1-MG)、β2微球蛋白(β2-MG)和N-乙酰β-D氨基葡萄糖苷酶(NAG)水平变化进行研究。计数资料两组间比较采用χ²检验或Fisher精确概率检验。计量资料两组间比较采用成组t检验或Mann-Whitney U检验。采用Logistic回归分析治疗组中尿α1-MG、β2-MG及NAG异常的独立影响因素。结果治疗组和对照组血肌酐水平和eGFR的差异均无统计学意义(t值分别为0.999、-1.259，P值均＞0.05)，且均在正常值范围内。但治疗组的尿α1-MG、β2-MG异常率(47.2%、42.4%)高于对照组(13.6%、13.6%)，组间差异均有统计学意义(χ²值分别为15.693、12.567，P值均＜0.001)。同时，这两个指标高于两倍正常值上限的比例，治疗组(18.4%、21.6%)亦高于对照组(2.3%、4.5%)，组间差异均有统计学意义(P值均＜0.05)；而尿NAG异常率治疗组和对照组比较(8.0% vs 6.8%)，差异无统计学意义(P＞0.05)，其大于两倍正常值上限的比例(8.8% vs 6.8%)，差异亦无统计学意义(P＞0.05)。两个以上肾小管损伤指标存在异常的比例在治疗组(33.6%)明显高于对照组(11.4%)，组间差异有统计学意义(χ²=8.519，P＜0.05)；但是单个指标异常率比较(16.0% vs 11.4%)，差异无统计学意义(P＞0.05)。结论恩替卡韦长期治疗CHB存在导致肾小管功能损伤的风险，两个以上肾损伤指标异常可帮助临床判断患者可能存在肾小管功能损伤，以便及时调整相关治疗。
- 乙型肝炎, 慢性 /
- 恩替卡韦 /
- 急性肾损伤
Abstract: Objective To investigate the possible influence of long-term antiviral therapy with entecavir on renal function in patients with chronic hepatitis B (CHB) and the sensitive indicators for early identification of renal injury. Methods A cross-sectional real-world study was conducted for the clinical data of 125 CHB patients treated with entecavir for more than 1 year (treatment group) and 44 patients with chronic HBV infection who did not receive antiviral therapy (control group), including the changes in serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and the levels of urinary α1 microglobulin (α1-MG), β2 microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG). The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Logistic regression analysis was used to investigate independent influencing factors for abnormal urinary α1-MG, β2-MG, and NAG in the treatment group. Results There were no significant differences in SCr and eGFR between the treatment group and the control group (t=0.999 and -1.259, P > 0.05), and both indices were within the normal range in these two groups. The treatment group had significantly higher abnormal rates of urinary α1-MG and β2-MG than the control group (47.2%/42.4% vs 13.6%/13.6%, χ²=15.693 and 12.567, both P < 0.001), and compared with the control group, the treatment group had a significantly higher proportion of patients with α1-MG or β2-MG > 2×upper limit of normal (18.4%/21.6% vs 2.3%/4.5%, both P < 0.05); however, there were no significant differences between the treatment group and the control group in the abnormal rate of urinary NAG (8.0% vs 6.8%, P > 0.05) and the proportion of patients with urinary NAG > 2×upper limit of normal (8.8% vs 6.8%, P > 0.05). Compared with the control group, the treatment group had a significantly higher proportion of patients with abnormalities in two or more indicators for renal tubular injury (33.6% vs 11.4%, χ²=8.519, P < 0.05), while there was no significant difference between the two groups in the proportion of patients with abnormalities in one indicator (16.0% vs 11.4%, P > 0.05). Conclusion Long-term treatment of CHB with entecavir may be associated with the risk of renal tubular dysfunction, and abnormalities in more than two indicators for renal injury may help to identify renal tubular dysfunction in patients, so as to adjust related treatment in time.
- Hepatitis B, Chronic /
- Entecavir /
- Acute Kidney Injury

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表 1 两组患者基本特征情况比较

Table 1. Comparison of two groups of basic characteristics

项目	治疗组(n=125)	对照组(n=44)	统计值	P值
年龄(岁)	42.30±0.83	39.34±1.12	t=0.746	0.650
女/男(例)	47/78	14/30	χ²=3.924	0.492
血肌酐(μmol/L)	69.46±1.72	72.44±1.27	t=0.999	0.319
eGFR(mL·min^-1·1.73 m^-2)	113.65±2.41	110.47±1.69	t=-1.259	0.210
尿α1-MG(mg/L)	11.02(5.84~21.24)	2.91(2.39~9.52)	Z=5.748	＜0.01
尿β2-MG(mg/L)	0.26(0.15~0.48)	0.23(0.18~0.27)	Z=1.618	＜0.01
尿NAG(U/L)	5.53(4.03~7.80)	3.15(2.88~6.99)	Z=2.909	0.078

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表 2 两组尿α1-MG、β2-MG和NAG异常率的比较

Table 2. Comparison of abnormal rates of urine α1-MG、β2-MG and NAG between two groups

指标	治疗组(n=125)	对照组(n=44)	χ²值	P值
尿α1-MG[例(%)]	59(47.2)	6(13.6)	15.693	＜0.001
尿β2-MG[例(%)]	53(42.4)	6(13.6)	12.567	＜0.001
尿NAG[例(%)]	10(8.0)	3(6.8)	0.464	0.793

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表 3 两组肾小管损伤指标数值高于两倍正常值上限的比例比较

Table 3. Comparison of the proportion of renal tubular injury index values above twice the upper limit of normal between the two groups

指标	治疗组(n=125)	对照组(n=44)	P值
尿α1-MG[例(%)]	23(18.4)	1(2.3)	0.005
尿β2-MG[例(%)]	27(21.6)	2(4.5)	0.010
尿NAG[例(%)]	11(8.8)	3(6.8)	0.762

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表 4 两组肾小管损伤指标数量差异的比较

Table 4. Comparison of the number of renal tubular injury indicators between the two groups

异常指标数	治疗组 (n=125)	对照组 (n=44)	χ²值	P值
单个[例(%)]	20(16.0)	5(11.4)	0.660	0.417
两个以上[例(%)]	42(33.6)	5(11.4)	8.519	0.004

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表 5 肾小管损伤指标异常的影响因素的Logistic分析

Table 5. Logistic analysis results of influencing factors of abnormal renal tubular injury index

变量	尿α1-MG异常		尿β2-MG异常		尿NAG异常
变量	P值	OR(95%CI)	P值	OR(95%CI)	P值	OR(95%CI)
性别	0.002	5.206(1.788~15.160)	0.464	1.373(0.587~3.214)	0.380	0.568(1.161~2.006)
年龄	0.772	1.006(0.968~1.044)	0.808	0.995(0.959~1.033)	0.851	0.994(0.933~1.059)
用药时间(≥1年)	＜0.001	1.311(1.145~1.501)	＜0.001	1.272(1.119~1.447)	0.030	1.231(1.021~1.484)

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