Abstract
Background & AimsQuantitative HBsAg has been recognized to assist in the management of chronic hepatitis B virus (HBV) infection. However, its role in disease monitoring of HBeAg-negative patients remains unclear. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection.MethodsThis is a retrospective cohort study conducted in a university hospital. Treatment-naïve HBeAg-negative carriers followed for more than 3 years were recruited. Their hepatitis activities were categorized by longitudinal HBV-DNA levels into high viral-load (HVL: HBV-DNA >/ = 2000 IU/mL persistently), low viral-load (LVL: HBV-DNA <2000 IU/mL persistently) and fluctuated viral-load (FVL: HBV-DNA between HVL and LVL). The baseline and end-of-follow-up (EOF) HBsAg levels were quantified for analyses.ResultsWe recruited 187 patients with a median follow-up of 8 years. LVL patients had a significantly lower HBsAg at baseline and EOF and a significantly greater annualized HBsAg decline compared with the FVL and HVL. The longitudinal HBsAg change was independent of genotype B or C. The lower baseline HBsAg level predicted the HBsAg decline and HBsAg loss, whereas the higher baseline HBV-DNA predicted the hepatitis flare. A baseline HBsAg <50 IU/mL predicted subsequent HBsAg loss with a sensitivity of 82% and specificity of 67%. The annualized HBsAg decline appeared non-linear, and accelerated as the HBsAg level lowered (0.054, 0.091, 0.126 log10 IU/mL in patients with baseline HBsAg >1000, 100–999, <100 IU/mL, respectively, P for trend = .014).ConclusionsIn genotype B or C HBeAg-negative carriers, baseline HBsAg levels correlate with future disease activities and help to predict HBsAg decline or loss. Inactive carriers with lower baseline HBsAg levels have a greater and accelerating HBsAg decline over time, regardless of HBV genotypes.
Highlights
The natural history of hepatitis B virus (HBV) carriers who acquire 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
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
The baseline HBsAg and HBV-DNA levels were significantly lower in the low viral-load (LVL) group compared with the fluctuated viral-load (FVL) and high viral-load (HVL) groups (HBsAg: 2.84, 3.43 and 3.37 log10 IU/mL, P,.001; HBV-DNA: 1.77, 3.43 and 4.78 log10 IU/mL, P,.001)
Summary
The natural history of hepatitis B virus (HBV) carriers who acquire 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. 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,[4,5,6,7,8,9] as well as the responses to treatment.[10,11,12] 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.[13,14,15,16] 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. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection
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