Callea F
Servizio di Anatomia Patologica, Istituto G. Gaslini, Genova, Italia.
Ric Clin Lab. 1988 Apr-Sep;18(2-3):223-31. doi: 10.1007/BF02918885.
Liver biopsy specimens from patients positive for serum HBsAg reveal various expression patterns when properly stained by immunohistochemical techniques for the demonstration of HBsAg, HBcAg and HDAg. A negative staining for these three antigens seems to be associated with two conditions, i.e., self-limiting acute lobular hepatitis (ALH) or low amounts of intrahepatic antigens. The discrepancy between serum positivity and tissue negativity for HBsAg can be explained either by sampling error or by the higher sensitivity of the radioimmunoassay as compared with immunohistochemical methods. The use of amplification systems such as the avidin-biotin-peroxidase complex enhances the sensitivity of immunohistochemical peroxidase-antiperoxidase (PAP) techniques and makes it possible to detect very small amounts of both HBsAg and HBcAg in liver cells from paraffin-embedded tissue sections which had been negative with the conventional PAP technique. In cases with a positive staining for viral antigens, two main expression patterns (non-aggressive and aggressive) can be distinguished. The non-aggressive pattern is reflected in the HBcAg-free HBsAg-positive type (HBsAg carrier) or the generalized type of nuclear core (HBcAg carrier), while the aggressive pattern is reflected in the presence of HDAg, the presence of HDAg and HBcAg, the focal type of nuclear core or the cytoplasmic HBcAg. Superinfection of HBsAg carriers or switching from generalized to focal core, with or without cytoplasmic expression of HBcAg, results in transition from non-aggressive to aggressive pattern. The aggressive pattern occurs in association with histological features of chronic active hepatitis (CAH). When it occurs in ALH cases or in milder forms of chronic hepatitis, an evolution into CAH has to be expected. Features of severe CAH, eventually with cirrhosis, are found in association with two new expression patterns: the cytoplasmic core and the simultaneous presence of HBcAg and HDAg. When features of CAH are observed in liver tissue specimens with HBcAg-free HBsAg-positive type, the liver disease may be due to viral superinfection or to non-viral etiology, e.g., alpha 1-antitrypsin deficiency.
对血清HBsAg呈阳性的患者进行肝活检，当采用免疫组化技术对HBsAg、HBcAg和HDAg进行恰当染色时，可发现多种表达模式。这三种抗原呈阴性染色似乎与两种情况有关，即自限性急性小叶性肝炎（ALH）或肝内抗原量低。血清HBsAg呈阳性而组织呈阴性之间的差异，可通过抽样误差或放射免疫测定法与免疫组化方法相比更高的敏感性来解释。使用诸如抗生物素蛋白-生物素-过氧化物酶复合物等放大系统可提高免疫组化过氧化物酶-抗过氧化物酶（PAP）技术的敏感性，并有可能在常规PAP技术呈阴性的石蜡包埋组织切片的肝细胞中检测到极少量的HBsAg和HBcAg。在病毒抗原呈阳性染色的病例中，可区分出两种主要的表达模式（非侵袭性和侵袭性）。非侵袭性模式表现为无HBcAg的HBsAg阳性类型（HBsAg携带者）或核芯的弥漫性类型（HBcAg携带者），而侵袭性模式表现为HDAg的存在、HDAg和HBcAg的存在、核芯的局灶性类型或细胞质HBcAg。HBsAg携带者的重叠感染或从弥漫性核芯转变为局灶性核芯，无论有无HBcAg的细胞质表达，都会导致从不侵袭性模式转变为侵袭性模式。侵袭性模式与慢性活动性肝炎（CAH）的组织学特征相关。当它出现在ALH病例或较轻形式的慢性肝炎中时，预计会演变为CAH。在严重CAH（最终可能发展为肝硬化）的特征中，发现与两种新的表达模式相关：细胞质核芯以及HBcAg和HDAg的同时存在。当在无HBcAg的HBsAg阳性类型的肝组织标本中观察到CAH特征时，肝脏疾病可能是由于病毒重叠感染或非病毒病因，例如α1-抗胰蛋白酶缺乏症。
