title: Longitudinal changes in serum HBV DNA levels and predictors of progression during the natural course of HBeAg-negative chronic hepatitis B virus infection.
abstract: 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 > or =80, > or =2000 or > 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 > or =2000 or > 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 > or =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 > or =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.
authors.affiliation: Academic Department of Medicine, Hippokration General Hospital of Athens, Athens, Greece. gepapath@med.uoa.gr
authors.forename: G V
authors.initials: GV
authors.lastname: Papatheodoridis
authors.forename: N
authors.initials: N
authors.lastname: Chrysanthos
authors.forename: E
authors.initials: E
authors.lastname: Hadziyannis
authors.forename: E
authors.initials: E
authors.lastname: Cholongitas
authors.forename: E K
authors.initials: EK
authors.lastname: Manesis
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D002353:Carrier State / Q000175:diagnosis; D004796:Clinical Enzyme Tests; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase