Abstract
BackgroundHepatitis B virus (HBV) infection has been believed as a major cause of hepatocellular carcinoma (HCC) for a long time, however, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments. Tree shrew (Tupaia) is a small animal closely related to primates evolutionarily, with about 8 years of lifespan. Our previous study proved that tree shrews can be chronically HBV-infected after being inoculated neonatally with HBV. The present study reports the further results from the longer-term observation of these animals.MethodsNeonatal tree shrews were inoculated with sera from HBV-infected patient or tree shrew. Their serum samples and liver biopsies were collected periodically for detection of HBV markers as well as for histopathological and immunohistochemical examinations. Group A consisted of six tree shrews with chronic HBV-infection, and group B consisted of nine tree shrews without chronic HBV infection.ResultsPeriodical examinations on serum and liver biopsies of the animals in group A showed the progress of HBV infection, and two cases of HCC occurred at their late stage of life. The courses of HBV infection and the hepatic histopathological and immunohistochemical changes in the tree shrews were similar to those in humans. In contrast, neither HCC nor obvious hepatitis histopathological change was found among the tree shrews in group B.ConclusionsThe course of HBV infection and the features of HCC discovered in tree shrews are similar to those of chronically HBV-infected humans. The tree shrew model might be used to investigate the underlying mechanisms favoring susceptibility for chronic HBV infection and disease progression.
Highlights
Hepatitis B virus (HBV) infection has been believed as a major cause of hepatocellular carcinoma (HCC) for a long time, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments
General information of the animals All tree shrews observed in this study were from our previous investigations in which they were all inoculated with HBV at birth [16]
Group A consisted of six tree shrews that were chronically HBV-infected, while group B consisted of nine tree shrews that were confirmed as nonchronically HBV-infected
Summary
Hepatitis B virus (HBV) infection has been believed as a major cause of hepatocellular carcinoma (HCC) for a long time, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments. Tree shrew (Tupaia) is a small animal closely related to primates evolutionarily, with about 8 years of lifespan. The intimate relationship between human hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC), one of the most aggressive malignancies worldwide, is well recognized. The tree shrew (Tupaia) is a small animal classified currently in the order Scandentia and the superorder Euarchonta, with about 8 years lifespan. Since the early 1980s, studies have shown that tree shrews can be infected with HBV in vitro and probably in vivo [10,11,12], and HCC can be experimentally induced
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