Immune Pathogenesis of Hepatocellular Carcinoma

doi:10.1084/jem.188.2.341

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J. Exp. Med., Volume 188, Number 2, July 20, 1998 341-350

Immune Pathogenesis of Hepatocellular Carcinoma

By Yasunari Nakamoto, Luca G. Guidotti, Christian V. Kuhlen, Patricia Fowler, and Francis V. Chisari

From the Division of Experimental Pathology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037

Hepatocellular carcinoma (HCC) is a common complication of chronic hepatitis B virus (HBV) infection. The pathogenetic mechanismspotentially responsible for HCC during chronic HBV infection arenot well defined. This study demonstrates that chronic immune-mediatedliver cell injury triggers the development of HCC in the absenceof viral transactivation, insertional mutagenesis, and genotoxicchemicals. These results strongly suggest that the immune responseto HBV is both necessary and sufficient to cause liver cancerduring chronic HBV infection, and that all other procarcinogenicevents associated with HCC are probably dependent on this process.

Key words: cytotoxic T lymphocytes; hepatitis B virus; chronic hepatitis; hepatocellular carcinoma; transgenic mice

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