Level of Hepatitis B Virus DNA in Inactive Carriers With Persistently Normal Levels of Alanine Aminotransferase

Background & Aims: Little is known about the level of hepatitis B virus (HBV) DNA in individuals with chronic, inactive HBV infections. Patients who test positive for the antibody to hepatitis B e antigen (anti-HBe) and have normal levels of alanine aminotransferase for more than 10 years have a low risk of HBV reactivation and are considered to be inactive carriers. We investigated HBV DNA levels in inactive carriers and identified factors that correlated with this state among anti-HBe-positive carriers with HBV DNA levels of 10⁴ copies/mL or greater (5.26 copies/mL = 1 IU/mL). Methods: HBV DNA levels were assayed in 250 inactive carriers with persistently normal alanine aminotransferase levels for more than 10 years. Clinical and virologic features were compared between inactive carriers (with HBV DNA levels ≥10⁴ copies/mL) and age-matched patients with HBe antigen-negative chronic hepatitis (controls, n = 90). Results: The median level of HBV DNA among inactive carriers was 3.70 log₁₀ copies/mL (range, undetectable to 5.98 log₁₀ copies/mL). Ninety (36%) had levels of 10⁴ copies/mL or greater. Compared with control patients, significant differences of inactive carriers included sex (more female patients), lower HBV DNA levels, and lower prevalence of genotype C virus and the basal core promoter mutation T1762/A1764. The prevalence of the precore mutation A1896 was similar between groups. Multiple logistic regression analyses identified male sex, HBV DNA levels greater than 10⁵ copies/mL, and the basal core promoter mutation as independent factors that correlated with active disease. Conclusions: Nearly 40% of inactive carriers had HBV DNA levels of 10⁴ copies/mL or greater. Female sex, HBV DNA levels of 10⁴ to 10⁵ copies/mL, and wild-type basal core promoter correlated with inactive carrier state.