The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The natural history of hepatitis B virus (HBV) carriers who acquire always find useful information the virus in early life can be divided into 4 dynamic phases based on virus-host interactions, including: immune tolerance, immune clearance, inactive carrier state and reactivation phase. [1], [2] After hepatitis B e antigen (HBeAg) seroconversion, patients usually enter the inactive state, with low viral load and normal alanine aminotransferase (ALT) level. However, a certain proportion of inactive carriers may experience HBV reactivation, which accelerates the disease progression to end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC).
[3] Therefore, patients in the HBeAg-negative phase should still receive regular monitoring of the hepatitis activity. The introduction of HBsAg quantification has provided a new diagnostic tool in the management of chronic hepatitis B (CHB), such as the prediction of disease activity, HBsAg loss, and development of HCC in the natural history,[4]�C[9] as well as the responses to treatment.[10]�C[12] Several cross-sectional studies have shown the dynamic change of HBsAg levels during the natural course of HBV infection: higher in the immune tolerance and clearance phase, lower in the inactive phase and increases again in the reactivation phase.[13]�C[16] In an European study with 3 years of longitudinal follow-up of 209 genotype D HBeAg-negative patients, HBsAg levels correlated with disease activity and helped to predict the inactive carrier state.
[8] In another longitudinal study on 68 genotype B or C HBeAg-negative patients, HBsAg levels tended to be higher in the active carriers. [14] These lines of evidence suggest that, HBsAg quantification can be utilized for monitoring in patients with chronic hepatitis B infection because of its dynamic change and complementary role to HBV-DNA. However, most of the previous studies looking at the clinical significance of HBsAg level were of cross-sectional design with a limited follow-up duration or case numbers. The definition of disease activities mostly relied on the short-term observation of HBV-DNA; however, the HBV-DNA tended to fluctuate overtime. Therefore, larger studies with longer observation period are still needed for validation, especially in Asian countries where most chronic HBV infections are acquired early in life.
To that end, we conducted a study to investigate the longitudinal HBsAg change in HBeAg-negative patients with genotype B or C infection, and to explore the role of baseline HBsAg level in predicting disease progression in this special clinical setting. Materials and Methods Patient Cohort A total of 187 HBeAg-negative Batimastat carriers were recruited from the Gastroenterology Clinics in National Taiwan University Hospital between 1993 and 2006.