title: Viral level is an indicator of long-term outcome of hepatitis B virus e antigen-negative carriers with persistently normal serum alanine aminotransferase levels.
abstract: The association between viral level and the long-term outcomes of hepatitis B virus (HBV) carriers who test negative for hepatitis B virus e antigen (HBeAg) but have persistently normal serum alanine aminotransferase levels (PNALT) remains unclear. We examined hepatocarcinogenesis, hepatitis reactivation, predictive factors and the time course of HBV DNA levels during follow-up in 104 HBeAg-negative Japanese carriers with PNALT. During a mean follow-up period of 6.4 ± 3.4 years, 5 patients (4.8%) had hepatocarcinogenesis and 14 (13.5%) had hepatitis reactivation. At 5 and 10 years, the cumulative rates of hepatocarcinogenesis were 2.4% and 9.9%, while those of hepatitis activation were 13.7% and 15.5%, respectively. An HBV DNA level of ≥5 log10  copies/mL was the sole predictor of hepatocarcinogenesis with a univariate analysis. An HBV DNA level of ≥5 log10  copies/mL and an alanine aminotransferase (ALT) level of >20 to ≤40 IU/L were independent predictors of hepatitis reactivation in a Cox model. Because there was no association between hepatocarcinogenesis and ALT activity, the HBV DNA level was considered an essential predictor. In addition, the baseline HBV DNA level was related to the future level and was not subject to wide fluctuations. Our results showed that an HBV DNA level of ≥5 log10  copies/mL predicts subsequent hepatocarcinogenesis and hepatitis reactivation in HBeAg-negative carriers with PNALT. As the baseline HBV DNA level reflects the future level, appropriate clinical management according to the viral level is expected to decrease future risk.
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Japan. karsten@mh-hannover.de
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: A
authors.initials: A
authors.lastname: Shibuya
authors.forename: A
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: Y
authors.initials: Y
authors.lastname: Okuwaki
authors.forename: J
authors.initials: J
authors.lastname: Takada
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Minamino
authors.forename: K
authors.initials: K
authors.lastname: Sakurai
authors.forename: W
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000821:virology; D002353:Carrier State / Q000821:virology*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase