Incidence and Risk Factors of Progression to Cirrhosis in Inactive Carriers of Hepatitis B Virus

OBJECTIVES: Most hepatitis B virus (HBV) carriers are incidentally identified as inactive carriers (positive hepatitis B e antibody with normal alanine aminotransferase (ALT) levels), but their long-time outcome and risk of cirrhosis are incompletely understood. METHODS: A total of 1,965 inactive carriers (mean age: 35.6 years; males: 1,076) were studied. Cirrhosis was diagnosed using a high-resolution real-time ultrasound. RESULTS: During an 11.5-year mean follow-up, 314 carriers developed reactivation of hepatitis B (ALT was more than twice the upper limit of normal and positive HBV DNA was found using hybridization assays). The risk of reactivation of hepatitis B correlated significantly with advanced age at study entry (P < 0.0001) and male sex (P < 0.0001). A total of 57 patients developed cirrhosis, with the cumulative incidence being 15% after 25 years. The risk of cirrhosis correlated significantly with advanced age at entry (P = 0.004) and reactivation of hepatitis B (P < 0.0001). Of the 1,651 carriers without reactivation of hepatitis B, 10 developed cirrhosis, and advanced age at entry was the only significant factor (P = 0.03). Of the 314 patients with reactivation of hepatitis B, cirrhosis developed in 47 of them, with the cumulative incidence being 8, 16, 27, and 46% at 5, 10, 15, and 20 years, respectively, after the onset of reactivation. Male sex (P = 0.037) and advanced age at reactivation (P = 0.006) were the two independent risk factors. CONCLUSIONS: The so-called inactive carrier state cannot be generally viewed as an innocent long-lasting condition of good prognosis; regular follow-up is necessary.