人类免疫缺陷病毒感染者的CD4+T淋巴细胞水平对保护性乙型肝炎表面抗体的影响

Retrospective analysis of the effect of CD4+T lymphocyte level on hepatitis B surface antibody in human immunodeficiency virus infected patients

目的探讨人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者发生乙型肝炎病毒(hepatitis B virus,HBV)暴露后乙型肝炎表面抗体(hepatitis B surface antibody,抗-HBs)阳性率和抗-HBs效价与CD4+T淋巴细胞计数水平的关系。方法纳入2010年1月至2018年12月武汉大学中南医院收治的HIV感染者共4893例,回顾性分析HIV感染者的人口学资料、HIV相关诊断和治疗信息。根据患者的CD4+T淋巴细胞计数和HBV血清学标志物检测结果进行分组,比较不同CD4+T淋巴细胞计数组患者的抗-HBs阳性率和HBV暴露率。并比较不同抗-HBs效价组患者的CD4+T淋巴细胞计数。统计学分析采用χ2检验、方差分析或t检验。结果CD4+T淋巴细胞计数<200/μL组患者有3293例,200~500/μL组有1200例,CD4+T淋巴细胞计数>500/μL组有400例,HBV暴露率分别为78.0%(2569/3293)、77.0%(924/1200)和76.2%(305/400),抗-HBs阳性率分别为38.2%(1258/3293)、53.8%(645/1200)和62.5%(250/400),抗-HBs效价分别为(120.00±36.45)、(148.00±26.40)和(212.00±92.08)IU/L,3组间HBV暴露率差异无统计学意义(χ2=0.992,P=0.609),但抗-HBs阳性率和抗-HBs效价间差异均有统计学意义(χ2=146.779,F=45.362;均P<0.01)。根据患者抗-HBs效价,将HIV感染者分为抗-HBs阴性组(<10 IU/L)2740例、抗-HBs低效价组(10~99 IU/L)1220例、抗-HBs组中效价组(100~499 IU/L)693例和抗-HBs高效价组(≥500 IU/L)240例,4组CD4+T淋巴细胞计数水平分别为(150.00±8.42)/μL、(185.00±7.08)/μL、(243.00±12.07)/μL和(308.00±22.60)/μL,组间差异有统计学意义(F=68.479,P<0.01)。90例接受抗反转录病毒治疗的HIV感染者的抗-HBs效价由治疗前的(91.96±21.87)IU/L升至(200.76±56.43)IU/L,差异有统计学意义(t=-2.542,P=0.035)。208例HBV血清学标志物均为阴性的患者在治疗前后多次检测了HBV血清学标志物,相邻2次检测间隔时间为(26.2±5.3)个月,尚未发现有乙型肝炎表面抗原由阴转阳的患者。结论HIV感染者发生HBV暴露的风险与疾病所处阶段无明显关系,但抗-HBs阳性率及其效价与CD4+T淋巴细胞计数水平有关。监测抗-HBs效价和HBV血清学标志物的变化,有助于深入认识抗-HBs的保护作用和科学评价HBV暴露后的感染风险。

Objective To investigate the relationship between positive rate and titer of hepatitis B surface antibody(anti-HBs)and CD4+T lymphocyte count level in human immunodeficiency virus(HIV)infected patients after hepatitis B virus(HBV)exposure.Methods A total of 4893 HIV-infected patients were admitted to Zhongnan Hospital of Wuhan University from January 2010 to December 2018.The demographic data,HIV-related diagnosis,treatment information,CD4+T lymphocyte count and serum markers of HBV infection of HIV infected patients were retrospectively analyzed.The patients were grouped according to the CD4+T lymphocyte count and serum markers of HBV infection,and the differences of anti-HBs positive rate and HBV exposure rate in patients with different CD4+T lymphocyte counts were compared.The differences of CD4+T lymphocyte count in patients with different titer of anti-HBs were compared.Statistical analysis was performed using chi-square test,analysis of variance or t test.Results Patients with HIV infection were divided into CD4+T lymphocyte count<200/μL group(3293 cases),200-500/μL group(1200 cases)and CD4+T lymphocyte count>500/μL group(400 cases).The HBV exposure rates in the three groups were 78.0%(2569/3293),77.0%(924/1200)and 76.2%(305/400),respectively.The anti-HBs positive rates were 38.2%(1258/3293),53.8%(645/1200)and 62.5%(250/400),respectively.The anti-HBs titers were(120.00±36.45)IU/L,(148.00±26.40)IU/L and(212.00±92.08)IU/L,respectively.The exposure rates of HBV in the three groups were similar(χ2=0.992,P=0.609),but the positive rates and titers of anti-HBs were significantly different(χ2=146.779 and F=45.362,respectively,both P<0.01).When the patients were grouped by anti-HBs titer,2740 cases were divided into anti-HBs negative group(<10 IU/L),1220 cases in low anti-HBs group(10-99 IU/L),693 cases in medium anti-HBs group(100-499 IU/L)and 240 cases in high anti-HBs group(≥500 IU/L).The CD4+T lymphocyte count levels of the four groups were(150.00±8.42)/μL,(185.00±7.08)/μL,(243.00±12.07)/μL and(308.00±22.60)/μL,respectively.The overall CD4+T lymphocyte count levels among the four groups were significantly different(F=68.479,P<0.01).Among the 90 HIV infected patients who received anti-retroviral therapy(ART),the anti-HBs titer increased from(91.96±21.87)IU/L to(200.76±56.43)IU/L after treatment,and the anti-HBs level before and after treatment was significantly different(t=-2.542,P=0.035).Among 208 patients with negative HBV markers,no patients had hepatitis B surface antigen switched to positive when monitored for an interval time of(26.2±5.3)months.Conclusions The risk of HBV exposure in patients with HIV infection is not significantly related to the disease stage,but the positive rate and titer of anti-HBs are significantly positively correlated with CD4+T lymphocyte count level.The monitoring of anti-HBs and the serum markers of HBV infection in the same individual is conducive to the in-depth understanding of the protective effect of anti-HBs and the scientific evaluation of the risk of infection after HBV exposure.