Chu C M, Liaw Y F
Liver Research Unit, Chang Gung Memorial Hospital and Medical College, Taipei, Taiwan.
J Gastroenterol Hepatol. 1997 Oct;12(9-10):S218-22. doi: 10.1111/j.1440-1746.1997.tb00503.x.
Three clinicopathological phases of chronic hepatitis B virus (HBV) infection are identified. First, is immune tolerance of HBV. High levels of viraemia are associated with normal alanine aminotransferase (ALT) levels and minimal histological lesions. More than 30-40% of hepatocytes have the hepatitis B core antigen (HBcAg), predominantly in their nuclei. Maternally derived hepatitis B e antigen (HBeAg) crossing the placenta may result in the elimination of T helper cells responsive to HBeAg/HBcAg. This phase can last for periods ranging from a few weeks to 10 or more years until the immune tolerance is lost. Second, is the immune clearance of HBV. Intermediate levels of viraemia are associated with fluctuating ALT levels and active and ongoing hepatitis. Approximately 20-30% of hepatocytes have HBcAg, predominantly in their cytoplasm. Expression of pre-core defective HBV mutants during chronic HBV infection may lead to a reduction in the secretion of HBeAg and may trigger the beginning of the immuno-elimination phase. The mechanism of intrahepatic shift of HBcAg from the nucleus to the cytoplasm and the decreased levels of viraemia in this phase may be, at least in part, secondary to liver damage and regeneration. Third, is latent infection with residual integrated HBV. Undetectable viraemia is associated with normal ALT levels and no virus-induced liver damage. With regard to hepatocyte expression of HBsAg in chronic HBV infection, membrane staining of HBsAg on hepatocytes has been shown to correlate well with the presence of viraemia. The degree of cytoplasmic hepatitis B surface antigen (HBsAg) expression inversely correlates with the level of viraemia. Therefore, HBsAg carriers with high levels of viraemia have low levels of cytoplasmic hepatitis B surface antigen (HBsAg) expression, while those with low levels of viraemia have high levels of cytoplasmic HBsAg expression. However, several exceptions have been identified. High levels of viraemia associated with high levels of cytoplasmic HBsAg expression were recognized in patients with fibrosing cholestatic hepatitis. In contrast, low levels of viraemia associated with low levels of cytoplasmic HBsAg expression were recognized in patients with hepatitis C virus but not hepatitis D virus superinfection.
慢性乙型肝炎病毒（HBV）感染可分为三个临床病理阶段。首先是HBV免疫耐受期。高病毒血症水平与正常丙氨酸氨基转移酶（ALT）水平及轻微组织学病变相关。超过30%-40%的肝细胞含有乙肝核心抗原（HBcAg），主要位于细胞核内。经胎盘传递的母源性乙肝e抗原（HBeAg）可能导致对HBeAg/HBcAg有反应的辅助性T细胞被清除。此阶段可持续数周至10年或更长时间，直至免疫耐受丧失。其次是HBV免疫清除期。中等水平的病毒血症与ALT水平波动以及活动性进行性肝炎相关。约20%-30%的肝细胞含有HBcAg，主要位于细胞质中。慢性HBV感染期间前核心缺陷型HBV突变体的表达可能导致HBeAg分泌减少，并可能引发免疫清除期的开始。此阶段HBcAg在肝内从细胞核转移至细胞质以及病毒血症水平降低的机制，至少部分可能继发于肝损伤和再生。第三是残留整合型HBV的潜伏感染期。无法检测到病毒血症与正常ALT水平及无病毒诱导的肝损伤相关。关于慢性HBV感染中肝细胞HBsAg的表达，已表明肝细胞上HBsAg的膜染色与病毒血症的存在密切相关。细胞质乙肝表面抗原（HBsAg）表达程度与病毒血症水平呈负相关。因此，病毒血症水平高的HBsAg携带者细胞质乙肝表面抗原（HBsAg）表达水平低，而病毒血症水平低的携带者细胞质HBsAg表达水平高。然而，也发现了一些例外情况。在纤维性胆汁淤积性肝炎患者中，可识别出高病毒血症与高细胞质HBsAg表达相关。相反，在丙型肝炎病毒而非丁型肝炎病毒重叠感染患者中，可识别出低病毒血症与低细胞质HBsAg表达相关。
