| Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) worldwide, especially in the Asia-Pacific region. Several hepatitis B viral factors predictive of clinical outcomes in HBV carriers have been identified. The REVEAL-HBV study from Taiwan illustrated the strong association between HBV DNA level at study entry and risk of HCC overtime. In this community-based cohort study, male gender, older age, high serum alanineaminotransferase (ALT) level, positive HBeAg, higher HBV DNA level, HBV genotype C infection and core promoter mutationare independently associated with a higher risk of HCC. Another large hospital-based ERADICATE-B cohort of Taiwanese patients further validated the findings of REVEAL-HBV. The risk of HCC started to increase when HBV DNA level was higher than 2000 IU/mL. Both HBV DNA and HBsAg levels were shown to be associated with HCC development. While HBV DNA level had better predictive accuracy than HBsAg level when investigating the overall cohort, in patients with HBV DNA level <2000 IU/mL, HBsAg level ≥1000 IU/mL was identified as a new independent risk factor for HCC. With the results from REVEAL-HBV, a risk calculation for predicting HCC in non-cirrhotic patients has been developed and validated by independent cohorts (REACH-B). Current antiviral therapies, interferon and nucleos(t)ide analogues, have been proven to reduce the progression of chronic hepatitis B (CHB). However, covalently closed circular DNA (cccDNA) of HBV persists, resulting in viral relapse after the discontinuation of treatment. Several novel agents through viral and host targets approaches are under investigations towards functional cure of HBV. On one hand, direct acting antivirals (DAA) targeting virus itself, such as HBV new polymerase inhibitor, entry inhibitor, engineered site-specific nucleases and RNA interference, could inhibit amplification of cccDNA as well as intrahepatic HBV infection and eliminate or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. On the other hand, host targeting agents (HTA) include lymphotoxin-β receptor agonist, toll-like receptor agonist, immune checkpoint inhibitors and adenovirus-based therapeutic vaccine. Through enhancing innate and adaptive immune responses, these agents could induce non-cytolytic destruction of cccDNA or attack HBV-infected hepatocytes. With the implementation of universal hepatitis B vaccination and these promising therapeutic approaches, we hope to reach global HBV control in the middle of this century. |
