Long-term effect of AIDS infected individuals with hepatitis B virus infection on abnormal liver enzymes in Guangzhou
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摘要:
目的 分析广州市人类免疫缺陷病毒(human immunodeficiency virus, HIV)感染者在长期抗病毒治疗的过程中, 合并乙型肝炎病毒(hepatitis B virus, HBV)感染对HIV感染者肝酶异常发生的影响。 方法 利用艾滋病(acquired immune deficiency syndrome, AIDS)综合防治数据信息管理系统中2010年1月1日―2021年6月30日于广州市第八人民医院接受抗病毒治疗的HIV感染者的随访数据, 于2023年12月进行回顾性队列研究, 采用Joinpoint回归模型分析肝酶异常风险的变化趋势, 采用倾向性评分匹配法来改善合并HBV感染者和单纯HIV感染者的组间可比性, 采用多水平logistic回归分析模型分析合并HBV感染对肝酶异常的影响。 结果 根据纳入和排除标准筛选出13 829名HIV感染者, 倾向性评分匹配后共9 050名HIV感染者被纳入分析。单纯HIV感染者和合并HBV的感染者中, 分别有61.8%和70.4%发生了肝酶异常, 其发生风险呈现为治疗开始的9个月内快速下降、治疗9~27个月缓慢下降、治疗27个月以后稳定的3个阶段。对于HIV感染者, 在抗病毒治疗开始的9个月内合并HBV感染是肝酶异常的危险因素(OR=1.637, 95% CI: 1.437~1.866), 而在抗病毒治疗持续9个月后合并HBV感染与肝酶异常间关联无统计学意义(P>0.05)。 结论 在AIDS随访和管理的工作中, 对于合并HBV感染者开启抗病毒治疗后的首年内应重点关注其肝功能情况。 -
关键词:
- 人类免疫缺陷病毒 /
- 乙型病毒性肝炎 /
- 高效抗逆转录病毒疗法
Abstract:Objective To analyze the impact of concurrent HBV infection on the occurrence of liver enzyme abnormalities in HIV-infected individuals during long-term antiviral therapy in Guangzhou City. Methods A retrospective cohort study was conducted in December 2023, using follow-up data from HIV-infected individuals who received antiviral treatment at the Eighth People′s Hospital of Guangzhou from January 1 2010, to June 30 2021, as recorded in the "Comprehensive AIDS Prevention and Control Data Information Management System." The study employed a joinpoint regression model to analyze the changing trend in the risk of liver enzyme abnormalities. Propensity score matching was applied to enhance comparability between individuals co-infected with HBV and those simple HIV infections. Additionally, a multilevel logistic regression model was used to analyze the impact of concurrent HBV infection on liver enzyme abnormalities. Results After applying the inclusion and exclusion criteria, 13 829 HIV-infected individuals were screened, and following propensity score matching, a total of 9 050 HIV-infected individuals were included in the analysis. Among individuals infected with HIV alone and those with HBV, 61.8% and 70.4% experienced liver enzyme abnormalities, respectively. The risk of occurrence showed a rapid decrease within 9 months of treatment, a slow decrease from 9 to 27 months of treatment, and a stable three stage period after 27 months of treatment. For HIV-infected individuals, the co-infection with HBV within the first 9 months of antiviral treatment is a risk factor for liver enzyme abnormalities (OR=1.637, 95% CI: 1.437-1.866), but after 9 months of continuous antiviral treatment, there was no association between ca-HBV and liver enzyme abnormalities (P>0.05). Conclusions In the follow-up and management of AIDS, the liver function of patients with HBV infection should be focused on in the first year after starting antiviral treatment. -
图 1 单纯HIV感染者和合并HBV感染者的肝酶异常发病密度的Joinpoint回归
HIV：人类免疫缺陷病毒; HBV：乙型肝炎病毒。
Figure 1. The Joinpoint regression results for the incidence density of liver enzyme abnormalities in patients with HIV infection alone and those co-infected with HBV, with treatment divided into three phases
表 1 倾向性评分匹配后9 050名HIV感染者的一般情况
Table 1. The frequency, percentage, or mean and standard deviation of sociodemographic characteristics, HIV infection, HIV treatment, and baseline blood tests of 9 050 AIDS patients after propensity score matching, as well as the standardized mean difference between the two groups
变量 总计① (n=9 050) 单纯HIV感染者① (n=7 181) 合并HBV感染者① (n=1 869) 标准化差异 性别 男 7 749(85.6) 6 146(85.6) 1 603(85.8) -0.004 女 1 301(14.4) 1 035(14.4) 266(14.2) 0.004 开始治疗时的年龄/岁 37.4±13.0 37.3±13.3 37.7±12.0 0.016 传播途径 异性性传播 4 205(46.5) 3 319(46.2) 886(47.4) 0.008 同性性传播 4 265(47.1) 3 413(47.5) 852(45.6) -0.013 毒品注射传播 106(1.2) 79(1.1) 27(1.4) 0.004 血液制品传播 19(0.2) 14(0.2) 5(0.3) 0.012 其他/不确定 455(5.0) 356(5.0) 99(5.3) 0.007 现居地 广州市 8 851(97.8) 7 022(97.8) 1 829(97.9) 0.003 非广州市 199(2.2) 159(2.2) 40(2.1) -0.003 婚姻状况 单身 3 982(44.0) 3 190(44.4) 792(42.4) -0.018 已婚/同居 4 408(48.7) 3 469(48.3) 939(50.2) 0.013 离异/分居/丧偶/未知 660(7.3) 522(7.3) 138(7.4) 0.009 基线药物方案 非核苷酸逆转录酶抑制剂方案 7 106(78.5) 5 669(78.9) 1 437(76.9) 0.001 核苷酸逆转录酶抑制剂方案 407(4.5) 285(4.0) 122(6.5) -0.003 蛋白酶抑制剂方案 508(5.6) 399(5.6) 109(5.8) 0.021 整合酶抑制剂方案 1 029(11.4) 828(11.5) 201(10.8) -0.014 治疗时间/d 1 890(1080) 1 880(1080) 1 890(1080) -0.006 肝酶异常 5 789(64.0) 4 476(62.3) 1 313(70.3) 0.168 基线AST异常 1 270(14.0) 809(11.3) 461(24.7) 0.354 基线ALT异常 1 210(13.4) 821(11.4) 389(20.8) 0.257 基线总胆红素异常 401(4.4) 261(3.6) 140(7.5) 0.169 基线CD4+ T淋巴细胞计数异常 4 286(47.4) 3 373(47.0) 913(48.8) 0.005 基线CD8+ T淋巴细胞计数异常 2 213(24.5) 1 746(24.3) 467(25.0) 0.009 基线白细胞计数异常 2 392(26.4) 1 876(26.1) 516(27.6) 0.005 基线血小板计数异常 1 372(15.2) 1 076(15.0) 296(15.8) 0.011 基线血红蛋白异常 2 929(32.4) 2 306(32.1) 623(33.3) 0.004 基线血肌酐异常 498(5.5) 387(5.4) 111(5.9) 0.013 基线三酰甘油异常 2 502(27.6) 1 979(27.6) 523(28.0) 0.005 基线总胆固醇异常 965(10.7) 766(10.7) 199(10.6) -0.003 基线空腹血糖异常 1 234(13.6) 973(13.5) 261(14.0) 0.013 注：HIV, 人类免疫缺陷病毒; HBV, 乙型肝炎病毒; AST, 天冬氨酸氨基转移酶; ALT, 丙氨酸氨基转移酶。
①以人数(占比/%)或表示。
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表 2 匹配后的9 050名HIV感染者的肝酶异常的多水平logistic回归分析
Table 2. A multilevel model nested within logistic regression was used to analyze the effects of baseline information, infection details, treatment information, blood test results during treatment, treatment duration, and co-infection with HBV on liver enzyme abnormalities during the treatment process in HIV patients
变量 β值 OR值(95% CI) P值 变量 β值 OR值(95% CI) P值 性别(参照：男) 药物方案(参照：NNRTIs方案) 女 -0.886 0.412(0.358~0.474) < 0.001 PIs方案 -1.634 0.195(0.179~0.213) < 0.001 开始治疗时的年龄/岁 -0.016 0.984(0.979~0.988) < 0.001 INSTIs方案 -0.639 0.528(0.482~0.578) < 0.001 传播途径(参照：异性性传播) 基线AST异常 0.440 1.553(1.341~1.797) < 0.001 同性性传播 0.200 1.222(1.097~1.360) < 0.001 基线ALT异常 1.016 2.762(2.393~3.189) < 0.001 毒品注射传播 0.129 1.137(0.754~1.715) 0.539 基线总胆红素异常 0.092 1.096(0.898~1.338) 0.367 血液制品传播 0.338 1.402(0.591~3.330) 0.443 随访CD4+ T淋巴细胞计数异常 0.269 1.308(1.229~1.392) < 0.001 其他/不确定 -0.004 0.997(0.808~1.229) 0.974 合并HBV感染 0.602 1.825(1.625~2.049) < 0.001 现居地(参照：广州) 治疗时间(参照：短期) 非广州 0.251 1.285(0.961~1.719) 0.090 中期 -0.318 0.728(0.692~0.765) < 0.001 婚姻状况(参照：单身) 长期 -0.127 0.881(0.842~0.922) < 0.001 已婚/同居 0.023 1.023(0.910~1.151) 0.700 合并HBV感染×治疗时间(参照：短期) 离异/分居/丧偶/未知 0.141 1.151(0.952~1.392) 0.147 中期 -0.543 0.581(0.524~0.644) < 0.001 药物方案(参照：NNRTIs方案) 长期 -0.654 0.520(0.476~0.568) < 0.001 NRTIs方案 -0.497 0.609(0.535~0.692) < 0.001 注：NRTIs, 核苷酸逆转录酶抑制剂; PIs, 蛋白酶抑制剂; INSTIs, 整合酶抑制剂; AST, 天冬氨酸氨基转移酶; ALT, 丙氨酸氨基转移酶。
①以人数(占比/%)或表示。
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表 3 匹配后的9 050名HIV感染者的肝酶异常的分层多水平logistic回归分析
Table 3. After stratifying the treatment phases, a multilevel model nested within logistic regression was used to analyze the effects of baseline information, infection details, treatment information, blood test results during treatment, and co-infection with HBV on liver enzyme abnormalities in HIV patients throughout the treatment process
变量 短期 中期 长期 OR值(95% CI) P值 OR值(95% CI) P值 OR值(95% CI) P值 性别(参照：男) 女 0.461 (0.385~0.552) < 0.001 0.352 (0.272~0.457) < 0.001 0.333 (0.269~0.412) < 0.001 开始治疗时的年龄/岁 0.995 (0.990~1.001) 0.105 0.983 (0.975~0.990) < 0.001 0.966 (0.959~0.972) < 0.001 传播途径(参照：异性性传播) 同性性传播 1.196 (1.042~1.373) 0.011 1.291 (1.067~1.563) 0.009 1.292 (1.103~1.513) 0.002 毒品注射传播 0.854 (0.507~1.440) 0.555 1.142 (0.512~2.550) 0.745 1.591 (0.801~3.162) 0.185 血液制品传播 1.256 (0.416~3.792) 0.685 2.268 (0.505~10.196) 0.286 2.510 (0.782~8.054) 0.122 其他/不确定 0.955 (0.735~1.239) 0.728 0.915 (0.624~1.341) 0.649 1.192 (0.844~1.683) 0.319 现居地(参照：广州) 非广州 1.260 (0.874~1.816) 0.216 1.242 (0.726~2.124) 0.429 1.573 (0.993~2.492) 0.054 婚姻状况(参照：单身) 已婚/同居 1.122 (0.965~1.305) 0.135 0.953 (0.772~1.176) 0.654 1.036 (0.871~1.231) 0.691 离异/分居/丧偶/未知 1.397 (1.100~1.773) 0.006 1.019 (0.725~1.433) 0.913 1.188 (0.887~1.591) 0.248 药物方案(参照：NNRTIs方案) NRTIs方案 0.871 (0.692~1.097) 0.240 0.333 (0.221~0.503) < 0.001 0.430 (0.351~0.527) < 0.001 PIs方案 0.190 (0.157~0.230) < 0.001 0.122 (0.097~0.153) < 0.001 0.169 (0.147~0.194) < 0.001 INSTIs方案 0.471 (0.402~0.552) < 0.001 0.322 (0.251~0.413) < 0.001 0.542 (0.466~0.630) < 0.001 基线AST异常 2.275 (1.899~2.726) < 0.001 1.324 (1.012~1.731) 0.040 0.889 (0.703~1.125) 0.329 基线ALT异常 3.587 (3.000~4.287) < 0.001 3.999 (3.083~5.187) < 0.001 3.827 (3.073~4.767) < 0.001 基线总胆红素异常 1.223 (0.949~1.576) 0.120 0.818 (0.565~1.183) 0.285 1.012 (0.755~1.357) 0.937 随访CD4+ T淋巴细胞计数异常 1.373 (1.244~1.515) < 0.001 1.022 (0.872~1.197) 0.789 1.256 (1.081~1.460) 0.003 合并HBV感染 1.637 (1.437~1.866) < 0.001 1.013 (0.840~1.221) 0.895 0.905 (0.775~1.056) 0.206 注：NRTIs, 核苷酸逆转录酶抑制剂; PIs, 蛋白酶抑制剂; INSTIs, 整合酶抑制剂; AST, 天冬氨酸氨基转移酶; ALT, 丙氨酸氨基转移酶; HBV, 乙型肝炎病毒。
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