Relationship Between Core Gene Mutations of Hepatitis B Virus and Response to Alpha Interferon Therapy in Chronic Hepatitis B

Yoo, Byung Chul; Kim, Hyung Joon; Do, Jae Hyuk; Park, Sill Moo

Abstract

BACKGROUND/AIMS: Treatment of chronic hepatitis B with interferon results in a sustained loss of hepatitis B virus DNA and hepatitis B e antigen (HBeAg) and remission of liver disease only in a proportion of cases. Recently, mutations of hepatitis B virus (HBV) core gene have been reported as being related to the failure of interferon treatment in chronic hepatitis B. This study investigated whether core gene mutations of HBV are related to non-response to interferon therapy and whether the recurrence of HBeAg and HBV DNA in initial responders to interferon therapy is associated with the emergence of HBV core gene mutants. METHODS: The precore/core gene sequence was determined by polymerase chain reaction (PCR) and direct sequencing of PCR product in serum samples obtained before interferon treatment from 10 responders and 10 non-responders to interferon therapy. In addition, precore/core gene sequence was determined in serum samples obtained before interferon treatment and after recurrence from 10 patients who showed recurrence of HBeAg and HBV DNA after initial response to interferon therapy. RESULTS: In samples from 10 responders, there were 7 missense mutations and 71 silent mutations. However, there were 43 missense mutations and 109 silent mutations in samples from 10 non-responders. In samples obtained before interferon treatment from the 10 patients who showed recurrence after initial response, 8 missense mutations and 74 silents mutations were found. The nucleotide sequences from the samples obtained after the recurrence showed 6 silent nucleotide substitutions compared with the sequences from the samples obtained before interferon treatment. CONCLUSIONS: Mutations in the core protein of HBV occur more frequently in non-responders than responders to interferon therapy of chronic hepatitis B and may be a factor responsible for the failure of interferon treatment. The recurrence of HBeAg and HBV-DNA in initial responders to interferon therapy is not associated with the emergence of the HBV core gene mutants.