Abstract
Fibrosing cholestatic hepatitis (FCH) is a rapidly progressive form of viral hepatitis B that occurs in severely immunosuppressed patients. Pathologically, the liver in FCH is characterizdd by widespread hepatocyte vacuolization and apoptosis, which, in contrast to more common forms of hepatitis B, is only rarely associated with significant inflammation. Therefore, it has been proposed that, in FCH, hepatocytes may be injured by a direct cytopathic effect of the virus rather than by the host immune response. In support of this hypothesis, we present evidence that cultured hepatoma cells that had been transfected with a plasmid selectively expressing the viral large surface protein form numerous large vacuoles and undergo apoptosis. The similarity of the cytopathology in FCH in vivo and in these transfected cells in vitro strongly implicates the large surface protein as the direct cause of this acute liver disease. This conclusion is further supported by the published demonstration that hepatocytes tend to accumulate large surface protein in FCH, which may reflect its overexpression by the virus. In conclusion, our data implicate the large surface protein as a major cause of hepatocyte injury in fibrosing cholestatic hepatitis.
Original language | English |
---|---|
Pages (from-to) | 1400-1407 |
Number of pages | 8 |
Journal | Hepatology |
Volume | 36 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2002 Dec 1 |
Bibliographical note
Funding Information:Abbreviations: HBV, hepatitis B virus; FCH, fibrosing cholestatic hepatitis; ER, endoplasmic reticulum; CMV, cytomegalovirus; GFP, green fluorescent protein; PBS, phosphate-buffered saline; FACS, fluorescence-activated cell sorter; ERGIC, endoplasmic reticulum/Golgi intermediate compartment; zVADfmk, benzyloxycarbonyl-Val-Ala-Asp-fluromethylketone. From the 1Pathology Service, San Francisco VA Medical Center, San Francisco, CA; 2Department of Pathology and 4Comprehensive Cancer Center, University of California, San Francisco, CA; and 3Department of Life Science, Korea University, Seoul, Korea. Received July 19, 2002; accepted August 26, 2002. Supported by a VA Merit Review and National Institutes of Health grant R01CA55578 (to T.S.B.Y.); the UCSF Liver Center is supported by National Institutes of Health grant P30DK26743. B.Y.A. is the recipient of an overseas travel award from the Department of Education, Korea. N.-C.F. and B.Y.A. contributed equally to this work. Dr. Foo’s current affiliation is Genetic Immunotherapy Laboratory, Johns Hopkins Singapore Pty Ltd., Singapore. Address reprint requests to: T. S. Benedict Yen, M.D., Pathology 113B, 4150 Clement St., San Francisco, CA 94121. E-mail: [email protected]; fax: 415-750-6947. This is a US government work. There are no restrictions on its use. 0270-9139/02/3606-0015$0.00/0 doi:10.1053/jhep.2002.36819
ASJC Scopus subject areas
- Hepatology