Chronic alcohol intoxication decreases the serum level of hepatitis B surface antigen in transgenic mice

Abstract

Hepatitis B virus (HBV) infections with an unusual serological profile, viz. positivity of HBV-DNA in the absence of hepatitis B surface antigen (HBsAg), have been described in alcoholics. This atypical pattern could be due to a low circulating level of viral particles rendering HBsAg undetectable with commercial kits, whereas HBV-DNA remains positive using the highly sensitive hybridization technique. We hypothesize that the well-known alcohol-induced impairment of protein secretion could also concern HBsAg particles and leads to a decrease in serum levels of the HBs antigen. To verify this hypothesis, we used HBsAg-positive transgenic mice as an animal model. Twelve HBsAg+ mice were separated into two groups; one group ( n = 6) was submitted to increasing alcoholisation over an 18-week period, while the other ( n = 6) was water fed. Seven HBsAg- littermates acted as controls: three received the alcohol regimen and the remaining four water. Chronic excessive alcoholisation lead to a significant decrease in serum HBsAg concentrations, while there was no obvious change in liver S mRNA. Ultrastructural studies showed a significant decrease in the number of microtubules in the livers of alcohol-fed mice. Finally, immunohistochemical studies performed at the end of the experiment showed a greater accumulation of HBsAg in the livers of HBsAg+ alcohol-fed (mainly located in the centrilobular area) than in the HBsAg+ water-fed mice. Our results (i) validate our initial hypothesis that chronic alcohol abuse leads to a decrease in serum HBsAg concentrations. This could explain, in part at least, the serological dissociations which were observed, (ii) Confirm the utility of screening serum HBV-DNA in alcoholics, (iii) Demonstrate that transgenic HBsAg+ mice offer a valid model for the study of the interactions between HBV and alcohol.