Clinical significance and evolution of core promoter and precore mutations in HBeAg-positive patients with HBV genotype B and C: a longitudinal study

Authors

  • Chien-Hung Chen,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Internal Medicine, the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Chuan-Mo Lee,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Internal Medicine, the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    3. Department of Chinese Medicine, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Chao-Hung Hung,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Tsung-Hui Hu,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Jing-Houng Wang,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Jyh-Chwan Wang,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Sheng-Nan Lu,

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Chi-Sin Changchien

    1. Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Correspondence
Chuan-Mo Lee, MD, Department of Internal Medicine, Division of Hepatogastroenterology, Chang Gung Memorial Hospital–Kaohsiung Medical Center, 123 Ta Pei Road, Kaohsiung, Taiwan.
Tel: +886 7731 7123, ext 8301
Fax: +886 7732 2402
e-mail: chmolee@ms15.hinet.net

Abstract

Background/Aims: The aims of this longitudinal study were to investigate whether the clinical outcome and evolution of core promoter and precore mutations were different during hepatitis B e antigen (HBeAg) seroconversion between hepatitis B virus (HBV) genotypes B and C in HBeAg-positive patients with chronic hepatitis B.

Patients and Methods: The core promoter and precore sequences were determined from serial sera of 156 HBeAg-positive patients with chronic HBV infection.

Results: In HBV genotype C, the T1762/A1764 mutant was detected earlier than the A1896 mutant, and the frequency was significantly higher than in HBV genotype Ba over the entire follow-up period. In HBV genotype Ba, A1896 was found earlier than the T1762/A1764 mutant, and the frequency was significantly higher than in genotype C only before HBeAg seroconversion, and the A1896 mutant played an important role in HBeAg seroconversion in HBV genotype Ba. In addition, the T1846 variant was an independent factor associated with HBeAg seroconversion. Furthermore, HBV genotype C was associated with the development of G or C1753 and T1766/A1768 mutations, and the reactivation of hepatitis after HBeAg seroconversion. Based on Cox's regression analysis, the significant risk factors of liver cirrhosis were older age at entry [hazard ratio (HR)=1.085, 95% confidence interval (CI)=1.036–1.136, P=0.001], alanine transaminase (ALT) >80 U/l (HR=3.48, 95% CI=1.37–8.86, P=0.009), and the T1762/A1764 mutant (HR=5.54, 95% CI=2.18–14.08, P<0.001).

Conclusions: Our study showed that different HBV genotypes were associated with various mutations in the core promoter and precore regions during HBeAg seroconversion. T1762/A1764 mutation could be useful in predicting clinical outcomes in HBeAg-positive patients with HBV infection.

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