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

Abstract

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 genusspecific 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.We recently described progressive, proliferative, and dysplastic typhlocolitis in aging (18-to 24-month-old) Syrian hamsters (31). The lesions in these hamsters were more severe in the older animals aged 7 to 24 months than in the younger, 1-to 6-month-old hamsters. The presence of Helicobacter spp. in the large bowel of all 24 hamsters included in the study was confirmed by culture and Helicobacter-specific PCR (31). Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified in this study (31). Enterohepatic Helicobacter spp. are associated with the development of inflammatory bowel disease in mice and, as determined more recently, humans (2, 18, 27, 51). These helicobacters can also induce hepatitis and hepatocellular carcinoma in susceptible strains of mice (1,14,19). We undertook a study to examine in detail the histological profile of the livers of hamsters aged 18 to 24 months and to determine whether Helicobacter sp. DNA was present in their livers (31). In addition, we purchased a small number of 6-month-old hamsters from the same vendor which originally supplied the aged hamsters and examined them for the presence of Helicobacter spp. in their intestines and liver and whether inflammation was associated with the presence of Helicobacter spp. in these target tissues. We document t...

Human liver flukes

“…Chronic cholestasis may also contribute to a low pH environment favourable to H. pylori (69) . H. bilis causes similar pre-malignant pathological changes to those seen in liver fluke infection in the biliary tree in an animal model (chronic hepatitis, hepatic dysplasia, fibrosis, and biliary hyperplasia) (70) . Cell inflammation and proliferation of biliary and gallbladder epithelial cells has been shown to be significantly higher in O. viverrini-related cholangiocarcinoma with H. pylori DNA detected in bile samples, compared to those without detectable biliary H. pylori infection (71) .…”

Molecular Epidemiologic Analysis and Antimicrobial Resistance of Helicobacter cinaedi Isolated from Seven Hospitals in Japan

“…Fifty H. cinaedi isolates were obtained from blood or fecal samples from patients treated in seven hospitals in Japan. Twelve isolates were obtained from Sapporo City General Hospital (hospital A) in Sapporo; the other 38 isolates were obtained from six hospitals in Tokyo: 2 isolates from the Social Insurance Chuo General Hospital (hospital B), 6 isolates from Toranomon Hospital (hospital C), 6 isolates from Teikyo University Hospital (hospital D), 3 isolates from Nihon University Itabashi Hospital (hospital E), 4 isolates from Toho University (hospital F), and 17 isolates from Surugadai Nihon University Hospital (hospital G). Details regarding the clinical manifestation of the patients were available only for the 26 isolates from hospitals A to D. These patients consisted of 7 women and 19 men, with a mean age of 61.3 years (age range, 28 to 88 years).…”

“…All isolates were subcultured on brucella agar (Becton, Dickinson, Franklin Lakes, NJ), with 5% horse blood, under microaerobic conditions with hydrogen obtained by the gas replacement method using an anaerobic gas mixture (H 2 , 10%; CO 2 , 10%; and N 2 , 80%) (5,6). H. cinaedi isolates were identified by morphological analysis and by DNA sequencing of both the 16S rRNA and the 23S rRNA genes.…”

Helicobacter pullorum Outbreak in C57BL/6NTac and C3H/HeNTac Barrier-Maintained Mice

“…The sequences of the 16S rRNA genes of two isolates (MIT 09-6633 and 09-6634) cultured from mice feces were analyzed using previously published techniques (8). Phylogenetic trees were constructed by the neighbor-joining method (13).…”