Sprengers D, van der Molen R G, Kusters J G, Hansen B, Niesters H G M, Schalm S W, Janssen H L A
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
J Med Virol. 2006 May;78(5):561-8. doi: 10.1002/jmv.20576.
Based on virological and biochemical parameters patients with chronic hepatitis B virus (HBV) are divided into distinct clinical phases: the immune-tolerance phase, the immune-clearance phase, and the inactive carrier state. Unclear is whether these phases have characteristic intrahepatic immune responses. The composition of liver-derived lymphocytes in patients with chronic HBV infection was studied. In 47 patients the composition of liver-derived lymphocytes was analyzed by flow cytometry of fine needle aspiration biopsies of the liver. The proportion natural killer (NK) cells in the liver was significantly higher in immune-tolerant than in immune-clearance patients and inactive carriers. No differences were found in proportion CD4+ T-cells and CD8+ T-cells, in these phases. However, when patients in the immune-clearance phase, with similar alanine transaminase (ALT), were grouped according to viral load, the proportion CD8+ T-cells was higher in those with high viral load. In contrast, the proportion CD4+ T-cells was increased in patients with low HBV-DNA. These differences were absent in the peripheral blood (PB). Intrahepatic HBV-specific CD8+ T-cells were mainly found in immune-clearance patients with low viral load. In conclusion, clear differences in the intrahepatic cellular infiltrate were found between the various clinical phases of chronic HBV infection. These findings are relevant to the design of new, individualized anti-viral strategies.
基于病毒学和生化参数，慢性乙型肝炎病毒（HBV）患者被分为不同的临床阶段：免疫耐受期、免疫清除期和非活动携带者状态。尚不清楚这些阶段是否具有特征性的肝内免疫反应。对慢性HBV感染患者肝源性淋巴细胞的组成进行了研究。对47例患者通过肝脏细针穿刺活检的流式细胞术分析肝源性淋巴细胞的组成。免疫耐受患者肝脏中自然杀伤（NK）细胞的比例显著高于免疫清除患者和非活动携带者。在这些阶段，CD4+T细胞和CD8+T细胞的比例未发现差异。然而，当将免疫清除期丙氨酸转氨酶（ALT）相似的患者按病毒载量分组时，病毒载量高的患者中CD8+T细胞的比例更高。相反，HBV-DNA低的患者中CD4+T细胞的比例增加。外周血（PB）中不存在这些差异。肝内HBV特异性CD8+T细胞主要见于病毒载量低的免疫清除患者。总之，在慢性HBV感染的不同临床阶段，肝内细胞浸润存在明显差异。这些发现与新的个体化抗病毒策略的设计相关。
