Longitudinal changes in serum HBV DNA levels and predictors of progression during the natural course of HBeAg-negative chronic hepatitis B virus infection

We evaluated the longitudinal changes of viraemia and predictors of progression in a prospectively followed cohort of 150 untreated patients with HBeAg-negative chronic hepatitis B virus (HBV) infection. According to the first year of follow-up, 85 patients were classified into inactive carrier state and 65 into chronic hepatitis B (CHB). Serum HBV DNA levels were determined at baseline in all patients, at year-1 in carriers or last pretherapy visit in CHB patients and during alanine aminotransferase (ALT) elevations in carriers progressing to CHB. HBV DNA levels at any occasion were >= 80, >= 2000 or >= 20 000 IU/mL in 81%, 23% or 0% of carriers and 100%, 95% or 83% of CHB patients. The cumulative progression rate from carrier to CHB was 11%, 16%, 24% at 2-, 3-, 4 years and was independently associated with higher baseline ALT (always within traditional normal range) and baseline HBV DNA >= 2000 or >= 5000 IU/mL. In 12 carriers progressed to CHB, HBV DNA increased by > 1 log(10) IU/mL. During 7.5 months of median follow-up, HBV DNA change >= 1 log(10) IU/mL was observed in 49% of CHB patients. In conclusion, serum HBV DNA levels are detectable in the majority of inactive HBV carriers exceeding 2000 IU/mL in only 23% and 20 000 IU/mL in none of them. Carriers have approximately 15% 3-year risk of progression to CHB, which is associated with higher baseline ALT and viraemia >= 2000-5000 IU/mL, and thus should be closely followed. Approximately 20% of HBeAg-negative CHB patients have HBV DNA < 20 000 IU/mL with fluctuations > 1 log(10) occurring in many of them.