Khakoo S I, Soni P N, Savage K, Brown D, Dhillon A P, Poulter L W, Dusheiko G M
Academic Department of Medicine, Royal Free Hospital, London, United Kingdom.
Am J Pathol. 1997 Mar;150(3):963-70.
The pathogenesis of chronic hepatitis C and the mechanisms underlying progressive liver disease in patients with chronic hepatitis C infection are poorly understood. To demonstrate which inflammatory cells might be responsible for the necroinflammatory damage in chronic hepatitis C infection, we have correlated the phenotype of the intrahepatic lymphocytes and macrophages with histological activity in liver biopsy and explant specimens from 19 patients with chronic hepatitis C infection. In all stages of disease, more CD8+ than CD4+ lymphocytes were found. However, histologically active versus histologically mild hepatitis was associated with a trend toward greater parenchymal concentrations of CD4+ lymphocytes (0.71 +/- 0.27 per 10(4) microns 2 versus 0.35 +/- 0.15; not significant), significantly less parenchymal CD8+ lymphocytes (0.90 +/- 0.1 versus 1.70 +/- 0.3; t = 2.32, P = 0.03) and a greater parenchymal CD4/CD8 ratio (4.1 +/- 2.8 versus 0.91 +/- 0.3; t = 1.65, P = 0.07). No difference was found in the number of cells containing cytotoxic granules between the two groups. Greater numbers of CD4+ lymphocytes were found in liver biopsy specimens with little or no staining for hepatitis C virus antigen (1.47 +/- 0.88 versus 0.27 +/- 0.27; t = 2.28, P < 0.05). No significant differences were found in the macrophage subsets between the three stages of disease. Our data suggest that active histological disease in chronic hepatitis C infection may be associated with an increase in CD4+ lymphocytes and suggest that CD4+ T cells may play an important role in the hepatic injury in these patients.
慢性丙型肝炎的发病机制以及慢性丙型肝炎感染患者发生进行性肝病的潜在机制目前仍知之甚少。为了证明哪些炎症细胞可能导致慢性丙型肝炎感染中的坏死性炎症损伤，我们将19例慢性丙型肝炎感染患者肝活检和外植体标本中肝内淋巴细胞和巨噬细胞的表型与组织学活性进行了关联分析。在疾病的所有阶段，发现CD8⁺淋巴细胞比CD4⁺淋巴细胞更多。然而，组织学上活跃型与组织学上轻度型肝炎相比，CD4⁺淋巴细胞在实质中的浓度有增加趋势（每10⁴平方微米分别为0.71±0.27与0.35±0.15；无统计学意义），实质中CD8⁺淋巴细胞显著减少（0.90±0.1与1.70±0.3；t = 2.32，P = 0.03），且实质中CD4/CD8比值更高（4.1±2.8与0.91±0.3；t = 1.65，P = 0.07）。两组之间含有细胞毒性颗粒的细胞数量没有差异。在丙型肝炎病毒抗原染色很少或无染色的肝活检标本中发现了更多的CD4⁺淋巴细胞（分别为1.47±0.88与0.27±0.27；t = 2.28，P < 0.05）。疾病的三个阶段之间巨噬细胞亚群没有显著差异。我们的数据表明，慢性丙型肝炎感染中活跃的组织学疾病可能与CD4⁺淋巴细胞增加有关，并提示CD4⁺T细胞可能在这些患者的肝损伤中起重要作用。
