Natural history of chronic HBV infection: A cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project)


  • Preliminary results of this study were presented at the 39th Annual Meeting of The European Association for the Study of the Liver.


The aim of the study was to assess the long-term outcome of chronic hepatitis B surface antigen (HBsAg) carriers in the general population in North Greece (Thrace), an area with an intermediate endemicity. This was a part of the Interreg I-II EC project. Two hundred sixty three chronic HBsAg(+) carriers, median age 34 years (20–65), were evaluated prospectively for a median follow-up of 5 years (2–12). Hepatitis B virus (HBV) markers and ALT were examined every 6 months and serum HBV-DNA every 12 months. Liver biopsy was undertaken at presentation and every 2–4 years. Fourteen of 263 (5.3%) subjects were HBeAg(+) and 249/263 (94.7%) HBeAg(−)/anti-HBe(+) of whom 48 (19.3%) had elevated ALT, and HBV-DNA levels ranging from 1.4 × 105–4 × 107 copies/ml. Inactive carriers (98/195 (50.3%)) had detectable HBV-DNA (median 2.6 × 103 range 0.042 × 104–1.9 × 104 copies/ml); 4/195 (2%) exhibited HBV reactivation during the observation period (all had HBV-DNA >104 copies/ml at presentation). Patients (7/14 (50%) HBeAg(+)) developed anti-HBe(+), annual rate 10%. Subjects (16/195 (8%)) lost HBsAg, all were inactive carriers; 10 developed anti-HBs (annual rate 1%). Liver biopsy was normal or with minimal changes in 92/95 (97%) inactive carriers and remained so at 4 years follow-up. In contrast, 4/48 (8.3%) HBeAg(−)/anti-HBe(+) patients with active disease had deterioration of liver histology. In this cohort study: (a) the annual seroconversion rate was 1% for the HBsAg and 10% for the HBeAg, (b) 23.6% of the HBsAg(+) carriers had active liver disease and 39% moderate fibrosis at presentation of whom a small proportion deteriorated over the observation period, (c) HBsAg carriers with HBV-DNA level <104 copies/ml had persistently normal ALT and unchanged liver histology over the follow-up period of up to 12 years. J. Med. Virol. 77:173–179, 2005. © 2005 Wiley-Liss, Inc.