Emergence of entecavir-resistant mutations in nucleos(t)ide-naive Japanese patients infected with hepatitis B virus: Virological breakthrough is also dependent on adherence to medication

Abstract

Objective. Currently, five nucleos(t)ide analogues (NUCs) are available for the treatment of chronic hepatitis B in the world. We examined the prevalence of hepatitis B virus (HBV) DNA and alanine aminotransferase normalization in patients receiving entecavir (ETV) and the frequency of ETV-resistant mutations during an approximately 27-month use of ETV in chronic hepatitis B patients in an urban hospital in Japan. Materials and methods. A retrospective analysis of 81 NUC-naive chronic hepatitis B patients who received 0.5 mg of ETV daily was performed. HBV DNA was measured and sequence analysis of HBV DNA was performed in virological breakthrough patients. Results. Hepatitis B e antigen (HBeAg)-positive patients with HBV DNA 5.0–7.0 log IU/mL group and all HBeAg-negative patients achieved serum HBV DNA negativity by 12 months. Four patients experienced virological breakthrough during ETV therapy. Two patients had no genotypic mutations, and medical interviews revealed that they had poor adherence to ETV. Conclusions. We found that some of the HBV virological breakthroughs during ETV treatment were related to poor adherence to medication, highlighting that clinicians should pay attention to the emergence of resistant mutants as well as adherence to ETV.

Key Words::

• Adherence
• entecavir
• HBV
• resistant mutants
• virological breakthrough

Acknowledgements

This work was supported by grants for Scientific Research 21590829, 21590828, and 21390225 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (TK, FI, and OY); a grant from the Viral Hepatitis Research Foundation of Japan (TK); and a grant from Chiba University Young Research-Oriented Faculty Member Development Program in Bioscience Areas (TK).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.