拉米夫定对慢性乙型肝炎疗效的组织病理学分析

Histological improvement in chronic hepatitis B patients treated with lamivudine

目的-从病理组织-学和-免疫组织化学改变的角度分析拉米夫定的疗效。方法13例慢性乙型肝炎患者予拉米夫定100mg/d,连用1年。治疗前后在超声导向下行肝脏活检,切片HE染色和网纤染色,对炎症活动度(HAI)和纤维化程度作计分评价。HBsAg和HBcAg用免疫组化(LSAB)法检测。结果13例患者拉米夫定治疗后血清HBVDNA全部转为阴性(<1.6pg/ml),组织学炎症活动度计分由5.23±2.99降为3.54±1.55(P<0.05);纤维化程度计分由2.61±1.15降为1.92±1.21(P>0.05)。免疫组化5例HBsAg由弥漫性胞浆型表达转变为散在包涵体样型表达,其中4例HBcAg由胞浆型表达为主转变为核型表达为主。结论拉米夫定持续用药可使肝组织炎症活动度计分尤其是碎屑坏死改善(P<0.05);血清HBVDNA阴转,肝组织HBsAg。

Objective To evaluate the liver histopathological changes of the chronic hepatitis B patients treated with lamivudine. Methods 13 chronic hepatitis B patients received 100 mg lamivudine orally daily for 52 weeks. The liver biopcies were obtained before and after treatment. The liver sections were stained with HE, Gorden Sweet and Masson methods. HBsAg and HBcAg were examined by immunohistochemistry method. Results The HAI score reduced from 5.23±2.99 to 3.54±1.55( P <0.05) after treatment with lamivudine, while the fibrosis score reduced from 2.61±1.15 to 1.92±1.21( P >0.05). Expression type of HBsAg changed from mainly in cytoplasm to inclusion body like in 5 patients, and expression type of HBcAg also changed from mainly in cytoplasm to nucleus in 4 patients. All patients became HBV DNA negative during treatment (<1.6/ml, liquid quantitative hybridisation assay, Abbott). Conclusions These results suggested that prolonged suppression of viral replication by lamivudine could significantly improve liver histological activity index, especially piecemeal necrosis. Lamivudine therapy lowered the expression of HBsAg, HBcAg in hepatocytes, induced the change of expression types. Persistent viral suppression with lamivudine might eventually slow down the development of liver fibrosis.