Genomic variations in the hepatitis B core gene: a possible factor influencing response to interferon alfa treatment.
OBJECTIVE
Interferon treatment causes a sustained loss of virus replication only in a proportion of patients with chronic hepatitis B. This study investigated whether genomic variations in the precore/core gene of hepatitis B virus affect the response to interferon alfa.


METHODS
The precore/core region was sequenced in 46 serum samples obtained before, during, and after interferon treatment of 12 patients.


RESULTS
In 23 samples from 7 responders (group A), there were 24 missense mutations, whereas in 23 samples from 5 patients who did not respond or relapsed after treatment (group B), there were 141 missense mutations (P < 0.001). All group B patients had cirrhosis, but only 2 of 7 patients in group A had cirrhosis (P = 0.026). Substitutions in amino acids 21-27 of the core protein, known to diminish HLA-A2-restricted cytotoxic T-cell function, were found in all nonresponders but in none of the responders. No significant changes occurred in the precore/core region in responders after seroconversion to antibody to hepatitis B e antigen, but multiple variations persisted in group B during treatment and new mutations appeared with the relapse of hepatitis.


CONCLUSIONS
Specific mutations in the core protein that can interfere with T-cell function occur frequently in patients with advanced chronic hepatitis B and may affect the response to interferon.
Institute of Liver Studies, King's College School of Medicine and Dentistry, London, England.
N V
NV
Naoumov
M G
MG
Thomas
A L
AL
Mason
S
S
Chokshi
C J
CJ
Bodicky
F
F
Farzaneh
R
R
Williams
R P
RP
Perrillo
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002908:Chronic Disease; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D006509:Hepatitis B / Q000235:genetics* / Q000628:therapy*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*
D016898:Interferon-alpha; D014758:Viral Core Proteins