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)

Abstract

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.

Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia

“…This is in line with observations made in other studies that reported that there are few patients who recall their acute episode of hepatitis, making it likely that intrafamily acquisition of the virus in the first years of life is the most common form of transmission of HBeAg-negative disease [5,19].…”

Viral load in hepatitis B e antigen-negative carriers with normal aminotransferase level

“…Compared with the results of a few earlier studies, [3][4][5][6] these figures are obviously much higher (Fig. 1).…”

“…1 This finding is also contradictory to earlier observations: abnormal ALT level was observed between the third and twelfth month of follow-up in all 25 HBeAg-negative subjects with normal baseline ALT but higher HBV-DNA level 5 ; the only 4 subjects with serum HBV-DNA Ͼ10 4 copies/mL at presentation in another study all exhibited ALT elevation during follow-up. 6 We recently followed 1241 asymptomatic HBeAg-negative HBsAg carriers with PNALT for 14,484 person-years and found that the cumulative probability of hepatitis relapse was 5% at the 2-year follow-up and 10% at the 5-year follow-up. 8 Given these findings in earlier studies and the finding that 16% of Lin's patients had an HBV-DNA level Ͼ10 6 and 32% had a level Ͼ10 5 copies/mL, it is anticipated that the dynamic interaction between the host and HBV in these patients would result in elevated ALT level during follow-up.…”

Follow-Up of Chronic Hepatitis B Carriers: A Cross-Sectional Descriptive-Analytical Study

“…Previous studies reported an HBeAg positivity rate of 2.5% to 29.4% (10,(13)(14)(15) studies was 10.5% (10), 13.3% (16), 30% (17), and 10% (18). Seroconversion is affected by factors, such as precore mutation, the phase of hepatitis, and the age when afflicted by HBV infection.…”