Nicoll A J, Angus P W, Chou S T, Luscombe C A, Smallwood R A, Locarnini S A
Victorian Infectious Diseases Reference Laboratory, Fairfield Hospital, Australia.
Hepatology. 1997 Feb;25(2):463-9. doi: 10.1002/hep.510250235.
Hepatitis B virus (HBV) has been demonstrated in bile duct epithelial cells (BDEC) during chronic infection. The persistence of virus in BDEC may play an important role in disease pathogenesis, and may be at least partly responsible for the relapse phenomenon observed in antiviral treatments using nucleoside analogues. The aims of this study were to examine the morphological changes within the liver in the duck hepatitis B model following bile duct ligation (BDL), and to assess the effect of biliary hyperplasia upon viral DNA and proteins. Seven-day-old ducklings, congenitally infected with the duck hepatitis B virus (DHBV), were subject to BDL. The pathological and virological changes were then followed at 5, 10, 15, and 20 days after ligation. All results were compared with age-matched unligated control birds congenitally infected with DHBV. To assess the early morphological changes, additional animals were sacrificed at 1, 2, 3, and 4 days post-BDL. The proportion of DHBV-infected BDEC, was examined by immunohistochemistry and in situ hybridization. BDL induced rapid biliary hyperplasia, with a doubling time for BDEC of 1.3 days. The proliferated BDEC displayed immunohistochemical features identical to resting BDEC. More than 50% of BDEC in unligated controls, and more than 46% of proliferated BDEC in ligated animals were positive for DHBV DNA and structural proteins. The intensity of immunohistochemical staining and in situ hybridization signal in the BDEC was consistently greater than that of the hepatocytes, both before and after BDL. BDL induces biliary hyperplasia in the duck model, and BDEC division does not reduce the viral burden in infected cells.
在慢性感染期间，已在胆管上皮细胞（BDEC）中证实存在乙型肝炎病毒（HBV）。病毒在BDEC中的持续存在可能在疾病发病机制中起重要作用，并且可能至少部分地导致在使用核苷类似物的抗病毒治疗中观察到的复发现象。本研究的目的是检查胆管结扎（BDL）后鸭乙型肝炎模型肝脏内的形态学变化，并评估胆管增生对病毒DNA和蛋白质的影响。将先天性感染鸭乙型肝炎病毒（DHBV）的7日龄雏鸭进行BDL。然后在结扎后第5、10、15和20天观察病理和病毒学变化。所有结果均与年龄匹配的先天性感染DHBV的未结扎对照禽类进行比较。为了评估早期形态学变化，在BDL后第1、2、3和4天处死额外的动物。通过免疫组织化学和原位杂交检查DHBV感染的BDEC的比例。BDL诱导胆管迅速增生，BDEC的倍增时间为1.3天。增殖的BDEC显示出与静止BDEC相同的免疫组织化学特征。未结扎对照中超过50%的BDEC以及结扎动物中超过46%的增殖BDEC对DHBV DNA和结构蛋白呈阳性。在BDL前后，BDEC中免疫组织化学染色强度和原位杂交信号始终大于肝细胞。BDL在鸭模型中诱导胆管增生，并且BDEC分裂不会降低感染细胞中的病毒载量。
