Published online Jul 28, 2016. doi: 10.4254/wjh.v8.i21.863
Peer-review started: March 28, 2016
First decision: May 17, 2016
Revised: May 28, 2016
Accepted: June 27, 2016
Article in press: June 29, 2016
Published online: July 28, 2016
About 250 to 350 million people worldwide are chronically infected with hepatitis B virus (HBV), and about 700000 patients per year die of HBV-related cirrhosis or hepatocellular carcinoma (HCC). Several anti-viral agents, such as interferon and nucleos(t)ide analogues (NAs), have been used to treat this disease. NAs especially have been shown to strongly suppress HBV replication, slowing the progression to cirrhosis and the development of HCC. However, reactivation of HBV replication often occurs after cessation of treatment, because NAs alone cannot completely remove covalently-closed circular DNA (cccDNA), the template of HBV replication, from the nuclei of hepatocytes. Anti-HBV immune responses, in conjunction with interferon-γ and tumor necrosis factor-α, were found to eliminate cccDNA, but complete eradication of cccDNA by immune response alone is difficult, as shown in patients who recover from acute HBV infection but often show long-term persistence of small amounts of HBV-DNA in the blood. Several new drugs interfering with the life cycle of HBV in hepatocytes have been developed, with drugs targeting cccDNA theoretically the most effective for radical cure of chronic HBV infection. However, the safety of these drugs should be extensively examined before application to patients, and combinations of several approaches may be necessary for radical cure of chronic HBV infection.
Core tip: Among the agents used to treat chronic hepatitis B virus (HBV) infection are nucleos(t)ide analogues, which have been shown to strongly suppress HBV replication. HBV replication, however, may be reactivated after cessation of treatment, because complete removal of covalently-closed circular DNA (cccDNA) from hepatocyte nuclei is extremely difficult. Immune responses have been shown to destroy cccDNA, but immune response alone is insufficient for complete eradication of template DNA. Several drugs were recently developed to block the HBV life cycle in hepatocytes, with drugs targeting cccDNA being, at least theoretically, the most effective for radical cure of chronic HBV infection. The safety of these agents should be extensively examined before their use in patients. Combinations of two or more classes of agent may be necessary for radical cure of chronic HBV infection.