Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B.
BACKGROUND
Anti-hepatitis e antigen-positive chronic hepatitis B is a progressive liver disease associated with precore mutant hepatitis B virus (HBV) and poor response to interferon. Therefore, precore mutant HBV may behave as an interferon-resistant virus. The relations between the prevalences of wild-type and precore mutant HBVs in baseline viremias and response to interferon were analyzed.


METHODS
Sera from 115 patients (59 treated and 56 untreated, followed up for 30 months) were tested using a quantitative oligonucleotide hybridization assay.


RESULTS
Spontaneous or interferon-induced recoveries were observed in 28.5% (6 of 21) and 47.3% (18 of 38) or in 0% (0 of 35) and 19% (4 of 21) of the patients with wild-type prevalent or mutant prevalent HBVs, respectively. Relapses occurred in 85.7% (12 of 14) and 19.4% (4 of 21) of treated patients with prevalent precore mutant and prevalent wild-type HBV, respectively (P = 0.0001). High precore mutant HBV levels (> 20% of total viremia) were associated with the lack of permanent response to interferon (P = 0.01).


CONCLUSIONS
Precore mutant HBV can influence the response to interferon when it reaches significant serum levels (> 20% of total viremia). Therefore, chronic hepatitis B should be treated as early as possible in its natural history before precore mutant HBV is selected as a prevalent virus.
Brunetto
M R
MR
Department of Gastroenterology, Molinette Hospital, Turin, Italy.
Giarin
M
M
Saracco
G
G
Oliveri
F
F
Calvo
P
P
Capra
G
G
Randone
A
A
Abate
M L
ML
Manzini
P
P
Capalbo
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides; D014758:Viral Core Proteins / Q000235:genetics
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D009841:Oligonucleotides; D014758:Viral Core Proteins; D007372:Interferons