Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution.
Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution.
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DOI：
10.1097/qad.0b013e3283324344
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发表时间：
2009-11-27
期刊：
影响因子：
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通讯作者：
Torbenson MS
中科院分区：
文献类型：
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作者：
Balagopal A;Ray SC;De Oca RM;Sutcliffe CG;Vivekanandan P;Higgins Y;Mehta SH;Moore RD;Sulkowski MS;Thomas DL;Torbenson MS
目的：HIV相关的肠道微生物易位的增强与肝纤维化的进展有关。虽然肝巨噬细胞（枯否细胞）清除大多数微生物易位产物，可以感染HIV，他们的命运在HIV的进展还没有仔细investigated.Methods：我们研究了枯否细胞密度（KCD）在76 HIV-丙型肝炎病毒合并感染的患者在不同阶段的肝脏疾病和CD 4+淋巴细胞耗竭（和恢复）。结果：KCD平均23个细胞每高倍视野（范围4.4-52.2），是最高的门静脉和门静脉周围区域相比，小叶中心区（P< 0.001）。KCD在年龄、肝纤维化分期或肝脏炎症评分方面无差异。然而，与没有明显的HIV相关免疫抑制的个体相比，外周血CD 4+淋巴细胞计数较低的人（P= 0.027）和最深的CD 4+淋巴细胞最低点的人（P= 0.006）中，KCD显著降低。在最初的肝活检后，8名患者开始抗逆转录病毒治疗，并有免疫恢复（外周血CD 4+淋巴细胞计数增加≥ 2倍）和第二次组织学评价，中位时间为36.8个月后（范围28.1-58.4个月）; KCD在所有（P= 0.007）。鉴于枯否细胞在控制微生物易位中的核心作用，这些数据提示在HIV-丙型肝炎病毒共感染者的肝纤维化发病机制中需要考虑枯否细胞损失。门脉和门脉周围枯否细胞的丰富提示它们在慢性病毒性肝炎门脉周围区域纤维化中的作用。
Objectives:HIV-related enhancement of gut microbial translocation is associated with progression of hepatic fibrosis. Although hepatic macrophages (Kupffer cells) clear most microbial translocation products and can be infected by HIV, their fate in HIV progression has not been carefully investigated.Methods:We studied Kupffer cell density (KCD) in 76 HIV–hepatitis C virus coinfected patients investigated at various stages of liver disease and CD4+ lymphocyte depletion (and restoration).Results:KCD averaged 23 cells per high-powered field (range 4.4–52.2) and was highest in portal and periportal regions as compared with centrilobular regions (P< 0.001). No differences were detected in KCD by age, liver fibrosis stage, or hepatic inflammatory score. Compared with individuals without apparent HIV-related immunosuppression, however, KCD was substantially lower in persons with lower peripheral blood CD4+ lymphocyte counts (P= 0.027) and lowest among those with deepest CD4+ lymphocyte nadir (P= 0.006). After the initial liver biopsy, eight patients began antiretroviral therapy and had immune restoration (≥ 2-fold increase in peripheral CD4+ lymphocyte count) and a second histologic evaluation with a median of 36.8 months later (range 28.1–58.4 months); KCD increased in all (P= 0.007).Conclusion:Given the central role of Kupffer cells in controlling microbial translocation, these data suggest Kupffer cell loss needs to be considered in the pathogenesis of liver fibrosis in HIV–hepatitis C virus coinfected persons. The abundance of portal and periportal Kupffer cells is suggestive of their contribution to fibrosis in periportal regions in chronic viral hepatitis.