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Infection and Immunity, June 2003, p. 3667-3672, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3667-3672.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Natural History of Helicobacter hepaticus Infection in Conventional A/J Mice, with Special Reference to Liver Involvement

Philippe Avenaud,¹ Brigitte Le Bail,² Kathryn Mayo,¹ Armelle Marais,¹ Rabia Fawaz,² Paulette Bioulac-Sage,² and Francis Megraud^1*

Laboratoire de Bactériologie,¹ GREF/INSERM E0362, Université Victor Segalen Bordeaux 2, Bordeaux, France²

Received 18 October 2002/ Returned for modification 10 December 2002/ Accepted 19 February 2003

It has been reported that Helicobacter hepaticus infection of mice leads to chronic hepatitis and hepatocarcinoma. Our aim was to monitor a cohort of 80 conventional A/J mice in which half of the mice were infected by H. hepaticus in order to study the evolution of the infection and the pathological changes in comparison to uninfected mice. H. hepaticus was detected by culture only in some colon and cecum specimens after 17 months of age, while PCR detected H. hepaticus in the intestines of all inoculated mice after only 5 months of infection. The percentage of mice in which H. hepaticus was detected in the gallbladder, bile ducts, and liver by PCR, as well as the number of bacteria present in the liver, tended to increase with increasing age and longer infection time. Anti-H. hepaticus immunoglobulin G antibodies were positive by enzyme-linked immunosorbent assay only in inoculated mice. Pathological findings were also more frequent as the mice grew older: fibrosis was present (especially in the peripheral part of the liver), and significant portal inflammation including lymphoid nodules was present in almost all infected animals. Biliary lesions of neutrophilic acute cholangitis or lymphocytic cholangitis were noted. However, lesions were also observed in uninfected animals, although at a significantly lower level, and the only hepatocellular carcinoma occurred in an uninfected mouse. The evolution towards hepatocarcinoma is not always the endpoint and may depend on the bacterial strain and on the environmental conditions.

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* Corresponding author. Mailing address: Laboratoire de Bactériologie, Hôpital Pellegrin, 33076 Bordeaux, France. Phone: 33 0 5 57 57 11 19. Fax: 33 0 5 56 51 41 82. E-mail: francis.megraud{at}chu-bordeaux.fr.

Editor: A. D. O'Brien

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Infection and Immunity, June 2003, p. 3667-3672, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3667-3672.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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