Hepatic lesions observed in hepatitis C virus transgenic mice infected by Helicobacter hepaticus.
BACKGROUND
The heterogeneity of hepatitis C virus (HCV) infection cannot always be explained by HCV genotypes or host genetic factors, raising the issue of possible cofactors. A new form of hepatitis leading to liver cancer was discovered in 1992 in mice, owing to an infection by Helicobacter hepaticus. Moreover, several studies showed an association between the presence of HCV and Helicobacter in the liver of patients with severe liver diseases suggesting a possible synergism between the two pathogens. In an HCV transgenic mouse model with a B6C3F1 background, the combination of H. hepaticus infection and the HCV transgene resulted in a significantly greater incidence and multiplicity of preneoplastic and neoplastic liver foci in males.


OBJECTIVE
Because the mouse genetic background is a major determinant in the development of liver disease, our aim was to test the synergism between HCV and H. hepaticus infection using transgenic mice with a more sensitive genetic background to H. hepaticus infection.


METHODS
For this purpose, four groups of mice were followed up to 14 months, the presence of H. hepaticus was monitored by PCR and hepatic lesions were looked for.


RESULTS
We found that H. hepaticus, but not the HCV transgene, increased the number of hepatic lesions. The presence of carcinoma was more likely to occur on a background of hepatitis, and the overall lesions were more frequent in the presence of steatosis. The effect of the mouse genetic background was greater than the effect of the HCV transgene and was sufficient to promote lesions particularly via its sensitivity to H. hepaticus infection.


CONCLUSIONS
Genetic susceptibility may be a more important factor than expected. Indeed, the synergism between HCV and H. hepaticus infection involved in liver disease may be highly host dependent.
INSERM, U853, F-33076, Bordeaux, France.
Emilie
E
Le Roux-Goglin
Pierre
P
Dubus
Corinne
C
Asencio
Marthe-Aline
MA
Jutand
Jean
J
Rosenbaum
Francis
F
Mégraud
D000818:Animals; D060085:Coinfection / Q000382:microbiology / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D044923:Helicobacter hepaticus / Q000472:pathogenicity*; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications / Q000473:pathology* / Q000821:virology; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic