Rothman Alan Lee, Morishima Chihiro, Bonkovsky Herbert L, Polyak Stephen J, Ray Ranjit, Di Bisceglie Adrian M, Lindsay Karen L, Malet Peter F, Chang Ming, Gretch David R, Sullivan Daniel G, Bhan Atul K, Wright Elizabeth C, Koziel Margaret James
Center for Infectious Disease and Vaccine Research and Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Hepatology. 2005 Mar;41(3):617-25. doi: 10.1002/hep.20581.
The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P = .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed.
宿主免疫和病毒因素与丙型肝炎病毒（HCV）所致肝病严重程度之间的关系尚不清楚。既往研究多聚焦于HCV免疫反应的个别成分，且患者数量往往相对较少。我们在一大群进入HALT-C（丙型肝炎抗病毒长期治疗抗肝硬化）试验时已有晚期肝纤维化（Ishak分期3 - 6期）的受试者中，检测了HCV特异性淋巴细胞增殖（LP）、肝内细胞毒性T淋巴细胞（CTL）和中和抗体（NA）反应以及HCV准种（QS）的多样性和复杂性。我们将LP、CTL、NA和QS结果与临床特征进行关联分析，这些临床特征包括血清丙氨酸氨基转移酶（ALT）、HCV RNA水平、HCV基因型和肝脏组织病理学。分别在37%、22%和22%的受试对象中检测到LP、CTL和NA反应。唯一具有统计学意义的关联是，可检测到HCV特异性CTL反应的患者血清ALT均值较高（P = 0.03）。总之，在这一经过选择、既往干扰素治疗失败的晚期慢性丙型肝炎患者群体中，对HCV的免疫反应和病毒多样性在单个时间点与临床或组织学特征几乎没有关联。
