Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis

Authors

  • Teh-ia Huo,

    1. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Jaw-ching Wu M.D., Ph.D.,Professor in Medicine,

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
    • Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei, Taiwan. Fax: 886-2-2874-9437
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  • Pui-ching Lee,

    1. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Gar-yang Chau,

    1. Department of Surgery, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Wing-yu Lui,

    1. Department of Surgery, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Shyh-haw Tsay,

    1. Department of Pathology, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Ling-tan Ting,

    1. Department of Pathology, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Full-young Chang,

    1. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Shou-dong Lee

    1. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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Abstract

The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the natural history of chronic hepatitis B virus (HBV)-infected patients was low. Previous studies regarding the prognosis in such patients were controversial. Among 1,355 chronic carriers from 1985 to 1997, spontaneous HBsAg clearance was observed in 55 patients. During a mean follow-up period of 23 months, 18 (32.7%; all were male subjects) developed serious complications, including 11 with hepatocellular carcinoma (HCC) (9 of them underwent surgical resection), 6 with cirrhosis, and 1 with subfulminant liver failure. The overall cumulative probability of complications was 29.8% at 4 years, and it was higher in males (P= .044) and patients aged 45 years or more (P= .006); the latter carried an 8.6-fold increased risk (95% CI: 1.2-64.6; P= .037) of adverse events. Histories of acute or chronic infection by hepatitis A virus, C virus (HCV), or D virus (HDV) were present in 42% of patients. Patients seropositive for antibodies against HCV (anti-HCV) or HDV (anti-HDV) had higher alanine transaminase (ALT) levels (>40 U/L;P= .008) after sero-clearance. HBV DNA was detectable in 31% of 51 subjects, in 20% of 20 with antibodies against HBsAg, in 40% of 20 with anti-HCV or anti-HDV, and also in an HCC patient's serum and tumor. Staining of liver HBsAg was positive in 30% of 10 HCC patients. In conclusion, our results demonstrated that hepatitis B viremia may persist, and adverse complications were not rare in HBsAg-clearance patients. All such patients should be closely monitored, which may allow for earlier detection of HCC.

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