Article

Journal of Gastroenterology

, Volume 39, Issue 1, pp 34-40

Low rate of YMDD motif mutations in polymerase gene of hepatitis B virus in chronically infected patients not treated with lamivudine

  • Marie MatsudaAffiliated withResearch Institute for Hepatology, Toranomon Branch Hospital
  • , Fumitaka SuzukiAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Yoshiyuki SuzukiAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Akihito TsubotaAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Norio AkutaAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Tetsuya HosakaAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Takashi SomeyaAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Masahiro KobayashiAffiliated withDepartment of Gastroenterology, Toranomon Hospital
  • , Satoshi SaitohAffiliated withDepartment of Gastroenterology, Toranomon Hospital
    • , Yasuji AraseAffiliated withDepartment of Gastroenterology, Toranomon Hospital
    • , Junko SatohAffiliated withResearch Institute for Hepatology, Toranomon Branch Hospital
    • , Kimiko TakagiAffiliated withResearch Institute for Hepatology, Toranomon Branch Hospital
    • , Mariko KobayashiAffiliated withResearch Institute for Hepatology, Toranomon Branch Hospital
    • , Kenji IkedaAffiliated withDepartment of Gastroenterology, Toranomon Hospital
    • , Hiromitsu KumadaAffiliated withDepartment of Gastroenterology, Toranomon Hospital

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Background

Lamivudine is used for the treatment of chronic hepatitis B (CH-B), and exhibits excellent antiviral activity. However, longterm administration increases the likelihood of the emergence of resistant viruses, with an accompanying relapse of hepatitis. However, recent studies have reported lamivudine-resistant viruses in patients with CH-B before such treatment. The aim of this study was to investigate whether YMDD mutants occur in nature.

Methods

The existence of lamivudine-resistant viruses was examined in 20 asymptomatic carriers of hepatitis B virus (ASC), 10 patients who lost hepatitis B surface antigen (HBsAg) during follow-up and in 20 lamivudine-treated patients with and without breakthrough hepatitis. Both polymerase chain reaction (PCR) restriction fragment length polymorphism and SMITEST hepatitis B virus (HBV)-YMDD mutation detection methods were used to detect resistant viruses.

Results

No YMDD mutants were detected in the sera of the 20 ASC at the initial and final medical examinations, nor were YMDD mutants detected in sera collected at the initial medical examination, about 6 months before, or immediately after the loss of HBsAg in the 10 patients. In the 20 patients treated with lamivudine, YMDD mutants were not detected in any of them before treatment, whereas mutants were detected in the sera of 10 patients during treatment.

Conclusions

Our results suggest that lamivudine-resistant YMDD mutant viruses were present in a few patients with HBV infection who before they have been treated with lamivudine.

Key words

hepatitis B virus lamivudine YMDD mutant