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Hepatitis A Virus-associated Cholecystitis

Samir Mourani, MD; Stuart M. Dobbs, MD; Robert M. Genta, MD; Atul K. Tandon, PhD; and Boris Yoffe, MD
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From the Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; BioGenex Laboratories, San Ramon, California. Requests for Reprints: Boris Yoffe, MD, Division of Digestive Diseases, 151B, Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030. Acknowledgments: The authors thank Ms. Irene Bleyzer for technical assistance and Dr. Mary Estes for provision of HAV-infected cell lines. Grant Support: By grants from the Department of Veterans Affairs, by the American College of Gastroenterology, and by BioGenex Laboratories. Dr. Yoffe is a Scientific Consultant for BioGenex Laboratories and Dr. Tandon is a Manager of Research and Development for BioGenex Laboratories.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;120(5):398-400. doi:10.7326/0003-4819-120-5-199403010-00008
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Cholestatic hepatitis [1] and cholecystitis [23] are poorly recognized manifestations of acute hepatitis A virus (HAV) infection. Although previous studies showed that HAV-associated RNA and antigen are present predominantly in hepatocytes and, to a lesser extent, in Kupffer cells, the pathogenesis of these abnormalities remains unknown [4]. To understand better the mechanisms of HAV-associated cholestasis and cholecystitis, we did an immunohistochemical analysis of liver and gallbladder specimens from an elderly patient with cholestatic hepatitis A and acalculous cholecystitis. A microscopic examination revealed portal inflammation and pericholangitis as well as cholestasis in the liver and lymphocytic cholecystitis. In contrast to weak staining in approximately 30% of hepatocytes, intense cytoplasmic staining of HAV antigen was detected in the epithelium of both the intrahepatic bile ducts and the gallbladder. These findings suggest that HAV can directly infect biliary epithelium and that such an infection may have an important role in the pathogenesis of cholestasis and gallbladder abnormalities in patients with acute HAV infection.

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Figure 1.
Immunostaining for antigen associated with hepatitis A virus in the liver and gallbladder from a patient with acute hepatitis A.top lefttop rightbottom leftbottom right

Microscopic examination of the liver showed severe portal inflammation with evidence of pericholangitis and intrahepatic cholestasis, in addition to focal hepatocyte necrosis and ballooning. Immunohistochemical staining of liver showed hepatitis A virus antigen in the biliary epithelium of bile ducts ( ), ductules and pseudoducts ( ), and faint cytoplasmic staining in approximately one third of the hepatocytes. The gallbladder showed a moderate lymphocytic infiltrate with virtual absence of neutrophils. Hepatitis A virus antigen was present in most epithelial cells ( ) and was located predominantly in the supranuclear areas of the cytoplasm of epithelial cells ( ).

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