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Gastroenterology. 1995 Feb;108(2):505-14.

Genomic variations in the hepatitis B core gene: a possible factor influencing response to interferon alfa treatment.

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  • 1Institute of Liver Studies, King's College School of Medicine and Dentistry, London, England.



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.


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


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.


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.

[PubMed - indexed for MEDLINE]
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