Viral Hepatitis
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 15, 2003; 9(5): 978-983
Published online May 15, 2003. doi: 10.3748/wjg.v9.i5.978
Hepatitis B virus infection of transplanted human hepatocytes causes a biochemical and histological hepatitis in immunocompetent rats
Catherine H. Wu, Edwin C. Ouyang, Cherie Walton, Kittichai Promrat, Faripour Forouhar, George Y. Wu
Catherine H. Wu, Edwin C. Ouyang, Cherie Walton, Kittichai Promrat, George Y. Wu, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
Faripour Forouhar, Department of Pathology, University of Connecticut Health Center, Farmington, CT, USA
Author contributions: All authors contributed equally to the work.
Supported by the grants from the NIDDK: DK-42182 (GYW), Connecticut Innovations, Inc. (CHW), a Blowitz-Ridgeway grant of the American Liver Foundation (CHW), and the Herman Lopata Chair in Hepatitis Research (GYW)
Correspondence to: George Y. Wu, PhD, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Rm. AM-045263 Farmington Avenue, Farmington, CT 06030-1845, USA. wu@nso.uchc.edu
Telephone: +1-860-6793158 Fax: +1-860-6793159
Received: October 25, 2002
Revised: October 29, 2002
Accepted: November 7, 2002
Published online: May 15, 2003
Abstract

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 post-inoculation and then plateaued at a level of about 0.6 pg/ml. 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 hepatocytes transplanted 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.

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