Naoumov N V, Thomas M G, Mason A L, Chokshi S, Bodicky C J, Farzaneh F, Williams R, Perrillo R P
Institute of Liver Studies, King's College School of Medicine and Dentistry, London, England.
Gastroenterology. 1995 Feb;108(2):505-14. doi: 10.1016/0016-5085(95)90080-2.
BACKGROUND/AIMS: 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.
