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A 13-year longitudinal study of the impact of double mutations in the core promoter region of hepatitis B virus on HBeAg seroconversion and disease progression in patients with genotype C chronic active hepatitis

Authors

  • J. W. Jang,

    1. Department of Internal Medicine, College of Medicine, Seoul
    2. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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  • Y. C. Lee,

    1. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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  • M. S. Kim,

    1. Department of Internal Medicine, College of Medicine, Seoul
    2. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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  • S. Y. Lee,

    1. Department of Internal Medicine, College of Medicine, Seoul
    2. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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  • S. H. Bae,

    1. Department of Internal Medicine, College of Medicine, Seoul
    2. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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  • J. Y. Choi,

    1. Department of Internal Medicine, College of Medicine, Seoul
    2. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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  • S. K. Yoon

    1. Department of Internal Medicine, College of Medicine, Seoul
    2. WHO collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea
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Dr Seung Kew Yoon, Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, No. 505 Banpodong, Seocho-ku, 137-040 Seoul, South Korea. E-mail: yoonsk@catholic.ac.kr

Abstract

Summary.  The pathogenic role of core promoter (CP) mutations (T1762/A1764) of hepatitis B virus (HBV) in hepatitis B e antigen (HBeAg) seroconversion or disease progression remains unclear. We investigated the clinical relevance of these mutants over a long-term follow-up period of up to 15 years. In this longitudinal cohort study, 29 HBeAg-positive patients with biopsy-proved chronic active hepatitis without cirrhosis were regularly monitored for >10 years. The viral isolates were characterized, using the frozen liver tissue obtained on the day of biopsy. Long-term outcomes were compared between patients with and without CP mutations of HBV at baseline. HBV genotyping showed that 100% of study subjects were infected with genotype C HBV. During a median follow-up period of 12.5 years, patients without double CP mutations of HBV at baseline showed a tendency towards achieving an earlier HBeAg seroconversion than those with (6.9 vs 9.4 years, P = 0.062) double CP mutations. Double CP mutations at baseline were also significantly associated with the eventual development of cirrhosis or hepatocellular carcinoma (P = 0.013), whereas the absence of double CP mutations predicted inactive carrier status at the last follow-up (P = 0.027). At 10 years, liver-related tests were also significantly better in patients without double CP mutations of HBV than in those with these mutations, as reflected by higher platelet counts and albumin levels (P = 0.036 and P = 0.044, respectively). Double T1762/A1764 mutations are significantly related to liver deterioration in HBeAg-positive genotype C active hepatitis patients. A longer period of immune clearance coupled with delayed HBeAg seroconversion appears to contribute to disease progression in patients harbouring these mutations in the CP region of HBV.

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