Role of Hepatitis B Surface Antigen Level in Long-term Outcomes of Hospital-based Hepatitis B Virus Carriers

• Main Authors: Tai-Chung Tseng, 曾岱宗
• Other Authors: 高嘉宏
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/87604109750419101285

博士 === 國立臺灣大學 === 臨床醫學研究所 === 101 === Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with a higher level of HBV DNA level have increased risks of hepatitis activity, cirrhosis, and HCC. However, in patients with HBV DNA level <2000 IU/mL, the viral load plays a little role in predicting these adverse events. Recently, using commercial quantitative assays, quantitative HBsAg (qHBsAg) has improved our understanding and management of chronic hepatitis B. Recent studies have shown that HBsAg level is highest in immune tolerance phase, starts to decline during immune clearance phase and decreases slowly but progressively after HBeAg seroconversion. HBsAg level is lowest in those with inactive carrier state but higher in those who develop HBeAg-negative hepatitis. In the Asian-Pacific region where HBV genotype B and C are dominant, HBeAg-negative carriers with a low viral load and spontaneous HBeAg seroconverters, HBsAg levels of 10-100 IU/mL may predict HBsAg loss over time, which is marker for HBV cure. However, little is known about whether higher levels of HBsAg increase the risk for disease progression in HBV carriers. In this dissertation, we used a hospital-based cohort study to investigate whether HBsAg level could complement HBV DNA level in predicting HBV-related adverse events. Our results showed that HBV DNA level, compared to HBsAg level, served as a better predictor for HCC. However, in HBeAg-negative patients with HBV DNA level <2000 IU/mL (low viral load), HBsAg level is the only viral factor associated with HCC development. In addition, we used the same cohort and found that HBsAg level ≥1000 IU/mL was associated with HBV-related complications, including HBV DNA relapse, hepatitis activity and cirrhosis development in lowly viremic patients. In other words, in patients with HBV DNA level <2000 IU/mL, HBsAg level >1000 IU/mL is associated with the HBV-related complications in every step of disease progression. In addition to patients with low viral loads, we also investigated the role of HBsAg in HBeAg-negative patients with HBV DNA level between 2000-20,000 IU/mL (intermediate viral load) and HBeAg-negative patients with HBV DNA level ≥20,000 IU/mL (high viral load). We found that HBsAg levels of 100 and 1000 IU/mL can further stratify HCC risk in patients with intermediate viral loads but HBsAg level played little role in patients with high viral loads. Finally, we tried to combine HBsAg and HBV DNA levels as a combined biomarker to predict HCC risk in the overall HBeAg-negative cohorts. The combined biomarker served as a better predictor for HCC than using HBV DNA level alone. Taking these lines of evidence together, qHBsAg can complement HBV-DNA to improve the management of CHB patients in our daily clinical practice. However, our results need to be validated by other large cohorts and the clinical utility of qHBsAg in patients receiving anti-viral therapy awaits further studies.