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HIV 引起的免疫缺陷与肝癌风险增加相关,法国 1998-2008 年 ANRS CO3 阿基坦队列研究。

HIV-induced immune deficiency is associated with a higher risk of hepatocarcinoma, ANRS CO3 Aquitaine Cohort, France, 1998-2008.

机构信息

INSERM U 897, Bordeaux School of Public Health (ISPED), Université Bordeaux Segalen, Bordeaux, France.

出版信息

J Hepatol. 2011 Nov;55(5):1058-62. doi: 10.1016/j.jhep.2011.02.017. Epub 2011 Feb 25.

DOI:10.1016/j.jhep.2011.02.017
PMID:21354449
Abstract

BACKGROUND & AIMS: HIV and viral hepatitis co-infected patients are at high risk for hepatocarcinoma. The contribution of immunodeficiency is not well documented. We aimed at estimating the relationship between the occurrence of hepatocarcinoma and both types of measures of immunodeficiency, current and cumulative (time below a given threshold), to assess their independent effects.

METHODS

HIV-infected adults included in the ANRS CO3 Aquitaine Cohort with no history of cancer, ≥ 3 months of follow-up between 1998 and 2008, ≥ 1 CD4+ cell count (CD4+), and documented hepatitis virus status were eligible. Extended Cox proportional hazards models with delayed entry were used to estimate the risk of hepatocarcinoma. Exposure to a CD4+ < 350 or <500 cells/mm(3) (current and cumulative duration) was time-updated. Hepatitis B or C virus co-infection and gender were fixed-effect variables.

RESULTS

Sixteen cases of hepatocarcinoma were diagnosed among the 2864 eligible patients, the incidence rate was 0.78 case/1000 person-years (95% Confidence Interval [CI]: 0.40-1.16). Current CD4+ < 350 or < 500 was independently associated with a higher risk of hepatocarcinoma (Hazard Ratio [HR]: 5.0, CI 1.5-16.8, p = 0.009 and HR = 10.3, CI 1.3-82.8, p = 0.029, respectively). The occurrence of hepatocarcinoma was independent of the cumulative exposure to a CD4+ < 350 or < 500 (p = 0.38 or p = 0.80, respectively).

CONCLUSIONS

Presenting with CD4+ < 500 was associated with a higher risk of hepatocarcinoma, whereas the cumulative duration with immunodeficiency was not. These results suggest that moving CD4+ count above 500 following antiretroviral therapy initiation is associated with a decreased risk of hepatocarcinoma, regardless of the duration of HIV-induced immunodeficiency.

摘要

背景与目的

HIV 和病毒性肝炎合并感染患者肝癌风险较高。免疫缺陷的作用尚未得到充分证实。本研究旨在评估当前和累计(低于特定阈值的时间)两种免疫缺陷测量方法与肝癌发生之间的关系,以评估它们的独立作用。

方法

符合条件的研究对象为纳入 ANRS CO3 阿基坦队列的、无癌症病史的成年 HIV 感染者,随访时间至少 3 个月(1998 年至 2008 年),至少有一次 CD4+细胞计数(CD4+),并记录了肝炎病毒状态。采用延迟进入的扩展 Cox 比例风险模型来估计肝癌风险。CD4+<350 或<500 细胞/mm3(当前和累计持续时间)的暴露情况为时间更新。乙型肝炎或丙型肝炎病毒合并感染和性别为固定效应变量。

结果

在 2864 名符合条件的患者中,诊断出 16 例肝癌,发病率为 0.78 例/1000 人年(95%置信区间:0.40-1.16)。当前 CD4+<350 或<500 与肝癌风险升高独立相关(风险比 [HR]:5.0,95%置信区间 [CI]:1.5-16.8,p=0.009 和 HR=10.3,CI 1.3-82.8,p=0.029)。CD4+<350 或<500 的累计暴露与肝癌的发生无关(p=0.38 或 p=0.80)。

结论

目前 CD4+<500 与肝癌风险升高相关,而免疫缺陷的累计持续时间与肝癌无关。这些结果表明,启动抗逆转录病毒治疗后将 CD4+计数提高到 500 以上与肝癌风险降低相关,而与 HIV 诱导的免疫缺陷持续时间无关。

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