Chronic alcohol intoxication decreases the serum level of hepatitis B surface antigen in transgenic mice.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Nalpas
B
B
Unité d'Hépatologie, Hôpital Laënnec, INSERM U-99, Paris, France.
Pourcel
C
C
Feldmann
G
G
Housset
C
C
Tiollais
P
P
Bréchot
C
C
Berthelot
P
P
Farza
H
H
D000437:Alcoholism / Q000097:blood* / Q000473:pathology; D000818:Animals; D001706:Biopsy; D015152:Blotting, Northern; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic / Q000097:blood*; D008854:Microscopy, Electron; D008870:Microtubules / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger