原位杂交研究慢性乙型肝炎病毒感染者肝组织内HBV DNA清除模式

用地高辛素探针原位杂交技术研究52例慢性HBV感染者肝内HBV DNA分布,发现在病毒高复制期,HBV DNA阳性肝细胞以弥漫性分布为主,肝细胞HBV DNA表型为胞浆型和核型,在病毒低复制期肝内HBV DNA阳性肝细胞以小叶聚集分布为主,多分布于灶性坏死和碎片状坏死区,在病毒非复制期,HBV DNA阳性肝细胞以局灶性分布为主,表型多为包涵体型和核型。提示在漫长的HBV感染过程中,肝内HBV DNA阳性肝细胞的分布经历弥漫性—小叶聚集性—局灶性的演变过程,该过程反映肝组织内HBV的清除模式。HBeAg(+)的慢性HBV无症状感染者肝组织病变轻可能是由于HBV DNA易装配为完整的病毒排出肝细胞的结果。说明免疫活性细胞攻击的靶细胞主要是含有HBV DNA的肝细胞。

Clearance model of hepatitis B virus DNA in patients with chronic hepatitis B virus infection: An in situ hybridizition study with digoxigenin-labelled DNA probe

Hepatitis B virus DNA ( HBV DNA ) was detected by in situ hybridization using a non-radioactive digoxigenin-labelled probe in 52 liver biopsies from patie-nts with chronic HBV infection. Intrahepatic distribution of HBV DNA was correlated with the status of hepatits B e antigen/antibody ( HBeAg/anti-HBe ) and with the histologic activity of the patients. In HBeAg positive patients with minor hepatic activity, HBV DNA positive hepatocytes was distributed in diffuse pattern, In HBeAg positive or negative patients with chronic active liver disease, the intrahepatic distribution of HBV DNA changed from diffuse into lobular pattern, often in areas near focal and piecemeal hepatic necrosis. In patients with anti-HBe positive,HBV DNA was distributed in spotty pattern. From those data, we conclude that change of HBV DNA distribution in liver in patients with chronic HBV infection reflects processes of HBV clearance. These results suggested that the main target celles of immunocytes may be hepatocytes carrying replica-tive HBV.