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Hepatitis B virus infection of transplanted human hepatocytes causes a biochemical and histological hepatitis in immunocompetent rats

查看全文 作　　者：Catherine [1]H.Wu;Edwin [1]C.Ouyang;Cherie [1]Walton;Kittichai [1]Promrat;Faripour [2]Forouhar;George Y. [1]Wu 高影响力作者 机构地区：[1]Department of Medicine,Division of Gastroenterology-Hepatology,University of Connecticut Health Center,Farmington,CT,USA;[2]Department of Pathology,University of Connecticut Health Center,Farmington,CT,USA高影响力机构 出　　处：《World Journal of Gastroenterology》索引2003年第9卷第5期,共6页高影响力期刊 基　　金：the grants from the NIDDK:DK-42182(GYW);Connecticut Innovations,Inc.(CHW);a Blowitz-Ridgeway grant of the American Liver Foundation(CHW);the Herman Lopata Chair in Hepatitis Research(GYW) 摘　　要：AIM: To characterize the host response to hepatitis B virus (HBV) infection in human hepatocytes transplanted into immunocompetent rodent rats tolerized by, and transplanted with primary human hepatocytes.METHODS: One week after the transplantation, rats were inoculated with HBV, and viral gene expression, replication,and host response was monitored.RESULTS: HBV DNA was detectable in serum for at least 60 days. HBsAg levels rose steadily for 3 weeks postinoculation and then plateaued at a level of about 0.6 pg/mi. HBV RNA was also found in liver at levels that remained constant through the time course. Immunofluorescence revealed clusters of hepatocytes that stained positive for HBcAg. The presence of HBV covalently closed circular DNA (cccDNA) in liver was demonstrated using nuclease digestion of single-stranded DNA followed by PCR. Serum ALT levels rose and reached a peak level of 180 IU/L on day 18, but remained elevated for 60 days. Histology revealed a progressive predominantly mononuclear lobular hepatitis.CONCLUSION: These data indicate that human hepatocytestransplanted into rats rendered tolerant to these cells, when infected by HBV, results in biochemical as well as histological evidence of hepatitis that accompanies viral gene expression,and DNA replication. 关 键 词：肝实质细胞种植 乙型肝炎病毒 生物化学 病理组织学 免疫原性 动物实验
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