Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B

In chronic replicative hepatitis B the significance of mutations in the bas ic core promoter (BCP), core upstream regulatory sequences (CURS) and negat ive regulatory element (NRE) for response to interferon (IFN) is unknown. A sequence analysis of the NRE, CURS, BCP, and precore region was performed from sera of 96 patients with chronic replicative hepatitis B (64 hepatitis B e antigen [HBeAg]-positive patients and 32 HBeAg-negative patients) trea ted with alfa-IFN (IFN-alpha), The overall sustained response (SR) rate to IFN was 30% with no significant difference between HBeAg-positive and HBeAg -negative patients. IFN responsiveness correlated to hepatitis B virus (HBV )-DNA levels, hepatitis B surface antigen (HBsAg) levels, the number of mut ations in the complete BCP, especially nucleotide (nt) region 1753 to 1766 and mutations at nt 1762 and 1764. In HBeAg-positive hepatitis, SR to IFN w as associated with a high number of mutations in the BCP (P < .04) and nucl eotide region 1753 to 1766 (P < .015) as well as mutations at nucleotide 17 64 (P < .007). In HBeAg-negative hepatitis, SR to IFN correlated with a low number of mutations in the BCP (P < .04) and nucleotide region 1753 to 176 6 (P < .02) and a wild-type sequence at nt 1764 (P < .003), Prediction of I FN response was possible on the basis of nt 1764 in 77% of HBeAg-positive p atients and 78% of HBeAg-negative patients. IFN response did not correlate with the occurrence of the 1896 mutation, mutations in the CURS or NRE, dis ease duration, ethnic origin of the patient, alanine transaminase (ALT) lev els and HBV genotype. Our data suggest that HBV genome mutations located wi thin the BCP are determinants of a response to IFN therapy.