Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen–negative chronic hepatitis B virus infection?

Authors

  • George V. Papatheodoridis,

    Corresponding author
    1. 2nd Department of Internal Medicine, Athens University Medical School, “Hippokration” General Hospital of Athens, Athens, Greece
    • 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, 114 Vas. Sophias Ave., 115 27 Athens, Greece
    Search for more papers by this author
    • fax: (30)-210-7706871

  • Emanuel K. Manesis,

    1. 2nd Department of Internal Medicine, Athens University Medical School, “Hippokration” General Hospital of Athens, Athens, Greece
    Search for more papers by this author
  • Spilios Manolakopoulos,

    1. 2nd Department of Internal Medicine, Athens University Medical School, “Hippokration” General Hospital of Athens, Athens, Greece
    Search for more papers by this author
  • Ioannis S. Elefsiniotis,

    1. University Department of Internal Medicine, “Helena Venizelou” Hospital, Athens, Greece
    Search for more papers by this author
  • John Goulis,

    1. 4th Department of Medicine, Aristotelian University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
    Search for more papers by this author
  • John Giannousis,

    1. 2nd Department of Internal Medicine, Athens University Medical School, “Hippokration” General Hospital of Athens, Athens, Greece
    Search for more papers by this author
  • Antonios Bilalis,

    1. Department of Gastroenterology, Polyclinic General Hospital of Athens, Athens, Greece
    Search for more papers by this author
  • Georgia Kafiri,

    1. Department of Pathology, “Hippokration” General Hospital of Athens, Athens, Greece
    Search for more papers by this author
  • Dimitrios Tzourmakliotis,

    1. Department of Gastroenterology, Polyclinic General Hospital of Athens, Athens, Greece
    Search for more papers by this author
  • Athanasios J. Archimandritis

    1. 2nd Department of Internal Medicine, Athens University Medical School, “Hippokration” General Hospital of Athens, Athens, Greece
    Search for more papers by this author

  • Potential conflict of interest: Dr. Papatheodoridis is a consultant for, advises, is on the speakers' bureau of, and received grants from Gilead Sciences, Roche, and Novartis. He is a consultant and advises Bristol-Myers Squibb. Dr. Manolakopoulos is a consultant, advises, is on the speakers' bureau of, and received grants from Gilead. He is a consultant for and received grants from Roche. He is a consultant for, advises, and received grants from Schering-Plough. He advises Bristol-Myers Squibb.

Abstract

The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA ≥2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score ≥7 and/or stage ≥2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA ≥200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. Conclusion: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA ≥20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up. (HEPATOLOGY 2008.)

Ancillary