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. 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.
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. 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.
Authors: Maria Homs; Maria Buti; David Tabernero; Josep Quer; Alex Sanchez; Noelia Corral; Rafael Esteban; Francisco Rodriguez-Frias Journal: World J Gastroenterol Date: 2012-11-14 Impact factor: 5.742
Authors: M K Maini; C Boni; C K Lee; J R Larrubia; S Reignat; G S Ogg; A S King; J Herberg; R Gilson; A Alisa; R Williams; D Vergani; N V Naoumov; C Ferrari; A Bertoletti Journal: J Exp Med Date: 2000-04-17 Impact factor: 14.307