Bonacini M, Govindarajan S, Kohla M, Lai M M C, Lindsay K L
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Minerva Gastroenterol Dietol. 2007 Mar;53(1):1-7.
The pathogenesis of viral hepatitis involves the activation of cellular immunity, including intrahepatic lymphocytes (IHL). Lym-phocyte phenotypes play a fundamental role in the pathogenesis of chronic hepatitis C virus (HCV) infection, the progression of liver fibrosis and subsequent hepatocellular carcinoma. The aim of this study was to evaluate the frequency of intrahepatic mononuclear cell phenotypes in patients with chronic HCV. Another aim was to assess the relationship of nonparenchymal cells with liver fibrosis.
Liver fibrosis was evaluated with the Histologic Activity Index. Fourteen liver biopsies showed mild fibrosis (group 1), and 11 bridging fibrosis (group 2). Fourteen samples were explants from HCV patients who underwent liver transplantation (group 3). CD4 and CD8 T-lymphocytes, CD20 (B lymphocytes), CD16 (macrophage), and CD57 (NK) cells were detected using monoclonal antibodies on paraffin-embedded tissue.
A minority of lobular cells stained for T- or B-lymphocytes. Most lobular cells stained with macrophage antibodies, and were more common in bridging fibrosis, compared to mild fibrosis. The percentages of lobular CD4 and CD8 cells were significantly lower in regenerative nodules of cirrhotic livers. There was a strong negative correlation between lobular CD8 and fibrosis score (R= -0.65), and a strong positive correlation between CD16-stained mononuclear cells (macrophages) and fibrosis score (R=0.66). In portal and periportal areas, CD4 but not CD8 lymphocytes decreased in parallel with fibrosis. B-lymphocytes were more commonly found in the portal areas than in the lobule. CD57-positive cells were rare in both lobule and portal areas, and their frequency was not different in the three groups studied.
In hepatitis C, lobular mononuclear cells are mostly macrophages and appear associated with bridging fibrosis. Cirrhotic livers display significantly lower numbers of lobular CD4 and CD8 lymphocytes. This finding could help explain a decrease in immune surveillance and the promotion of neoplastic growth in HCV-associated cirrhosis.
病毒性肝炎的发病机制涉及细胞免疫的激活，包括肝内淋巴细胞（IHL）。淋巴细胞表型在慢性丙型肝炎病毒（HCV）感染的发病机制、肝纤维化进展及随后的肝细胞癌中起重要作用。本研究的目的是评估慢性HCV患者肝内单核细胞表型的频率。另一个目的是评估非实质细胞与肝纤维化的关系。
用组织学活动指数评估肝纤维化。14例肝活检显示轻度纤维化（第1组），11例为桥接纤维化（第2组）。14个样本是接受肝移植的HCV患者的肝外植体（第3组）。使用单克隆抗体在石蜡包埋组织上检测CD4和CD8 T淋巴细胞、CD20（B淋巴细胞）、CD16（巨噬细胞）和CD57（NK）细胞。
少数小叶细胞被T或B淋巴细胞染色。大多数小叶细胞被巨噬细胞抗体染色，与轻度纤维化相比，在桥接纤维化中更常见。肝硬化肝脏再生结节中小叶CD4和CD8细胞的百分比显著降低。小叶CD8与纤维化评分之间存在强负相关（R = -0.65），CD16染色的单核细胞（巨噬细胞）与纤维化评分之间存在强正相关（R = 0.66）。在门静脉和门静脉周围区域，CD4淋巴细胞而非CD8淋巴细胞随纤维化程度平行减少。B淋巴细胞在门静脉区域比在小叶中更常见。CD57阳性细胞在小叶和门静脉区域均很少见，其频率在研究的三组中无差异。
在丙型肝炎中，小叶单核细胞主要是巨噬细胞，且似乎与桥接纤维化有关。肝硬化肝脏中小叶CD4和CD8淋巴细胞数量显著减少。这一发现有助于解释HCV相关肝硬化中免疫监视的降低和肿瘤生长的促进。
