Chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) are considered to be sequential adverse outcomes in patients with persistent hepatitis B virus (HBV) infection. HBV infection is endemic in Taiwan and most HBV carriers acquire the virus early in life. The impact of HBV factors on the natural course of patients with chronic HBV infection has been investigated in three cohort studies. The first Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) cohort study revealed that HBV viral load is a strong predictive factor for the risk of cirrhosis and HCC and baseline serum HBV DNA levels >2000 IU/ml may increase the risk of cirrhosis and HCC in adult HBV carriers. In the second Study of E Antigen seRoClearance of Hepatitis B (SEARCH-B), HBsAg level <100 IU/ml at 1-year post HBeAg seroconversion was shown to be a predictor of HBsAg seroclearance over time. Recently, the third Elucidation of Risk Factors for Disease Control or Advancement in Taiwanese Hepatitis B Carriers (ERADICATE-B) cohort study also suggested that HBsAg levels were a complementary predictive risk factor to HBV DNA levels for predicting HBV-related adverse events in patients with low viral load (HBV DNA level <2000 IU/ml). An HBsAg level >1000 IU/ml in HBeAg-negative patients with low viral load, is associated with higher risks of HCC, cirrhosis, and HBeAg-negative hepatitis. Based on results of the REVEAL-HBV cohort study, a risk calculator to predict HCC in non-cirrhotic patients was developed and validated by independent international cohorts (REACH-B). In the recent update of the REVEAL-HBV study, HBsAg level was incorporated into the HCC risk prediction model with excellent accuracy. In conclusion, evidence from these HBV clinical cohorts confirms the progression and integration of viral biomarkers for the prediction of the prognosis of Asian chronic hepatitis B (CHB) patients. If the predictive power of the HCC risk calculator could be validated in non-Asian populations, it could be used in clinical practice to individualize the management of HBV carriers with different levels of HCC risk.