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).
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 x 10(5)-4 x 10(7) copies/ml. Inactive carriers (98/195 (50.3%)) had detectable HBV-DNA (median 2.6 x 10(3) range 0.042 x 10(4)-1.9 x 10(4) copies/ml); 4/195 (2%) exhibited HBV reactivation during the observation period (all had HBV-DNA >10(4) 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 <10(4) copies/ml had persistently normal ALT and unchanged liver histology over the follow-up period of up to 12 years.
Zacharakis
G H
GH
Unit of Preventive Medicine, Social Security Institute, Alexandroupolis, Greece. GZacharakis@yahoo.gr
Koskinas
J
J
Kotsiou
S
S
Papoutselis
M
M
Tzara
F
F
Vafeiadis
N
N
Archimandritis
A J
AJ
Papoutselis
K
K
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D002353:Carrier State; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006115:Greece; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014766:Viremia
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D000410:Alanine Transaminase