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

Abstract

ABSTRACT 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.