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Journal of Clinical Microbiology, November 2009, p. 3673-3681, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.00879-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Chronic Hepatitis, Hepatic Dysplasia, Fibrosis, and Biliary Hyperplasia in Hamsters Naturally Infected with a Novel Helicobacter Classified in the H. bilis Cluster{triangledown}

J. G. Fox,1* Z. Shen,1 S. Muthupalani,1 A. R. Rogers,1 S. M. Kirchain,1 and F. E. Dewhirst2

Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg. 16-825, Cambridge, Massachusetts 02139,1 Department of Molecular Genetics, The Forsyth Institute, Boston, Massachusetts 021152

Received 4 May 2009/ Returned for modification 29 June 2009/ Accepted 30 August 2009

We recently described helicobacter-associated progressive, proliferative, and dysplastic typhlocolitis in aging (18- to 24-month-old) Syrian hamsters. Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified. The presence of Helicobacter genus-specific DNA was noted by PCR in cecal and paraffin-embedded liver samples from aged hamsters by the use of Helicobacter-specific PCR primers. By 16S rRNA analysis, the Helicobacter sp. isolated from the liver tissue was identical to the cecal isolates from hamsters. The six hamster 16S rRNA sequences form a genotypic cluster most closely related to Helicobacter sp. Flexispira taxon 8, part of the Helicobacter bilis/H. cinaedi group. Livers from aged helicobacter-infected hamsters showed various stages of predominantly portocentric and, to a lesser extent, perivenular fibrosis. Within nodules, there was cellular atypia consistent with nodular dysplasia. The livers also exhibited a range of chronic active portal/interface and lobular inflammation, with significant portal hepatitis being present. The inflammation was composed of a mixture of lymphocytes, neutrophils, and macrophages, indicative of its chronic-active nature in these aged hamsters infected with Helicobacter spp. The isolation of novel Helicobacter spp., their identification by PCR from the diseased livers of aged hamsters, and their taxonomic classification as belonging to the Helicobacter bilis cluster strengthen the argument that H. bilis and closely related Helicobacter spp. play an etiological role in hepatobiliary disease in both animals and humans.

* Corresponding author. Mailing address: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave., Bldg. 16-825, Cambridge, MA 02139. Phone: (617) 253-1757. Fax: (617) 258-5708. E-mail: jgfox{at}mit.edu

{triangledown} Published ahead of print on 16 September 2009.

Journal of Clinical Microbiology, November 2009, p. 3673-3681, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.00879-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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