Published online Jun 28, 2016. doi: 10.3748/wjg.v22.i24.5467
Peer-review started: March 25, 2016
First decision: May 12, 2016
Revised: May 17, 2016
Accepted: June 2, 2016
Article in press: June 2, 2016
Published online: June 28, 2016
Core tip: Of hepatitis B virus (HBV)-X protein (HBx) mutations related to clinical severity, the A1762T/G1764A BCP mutation is one of the most frequently encountered HBx mutations and plays a significant role in liver disease progression in chronic patients with HBV infections. It also further contributes to disease progression by inducing mutations of other HBx mutations related to clinical severity, such as G1386A/C (V5M/L), C1653T (H94Y), T1753V (I127V) and HBx C-terminal deletion or insertion. Moreover, T1753V (I127L,T,N,S) and C1653T (H94Y) mutations in the enhancer II/BCP region and A1383C, G1386A/C (V5M/L) and C1485T (P38S) in the negative regulation domain are significantly related to severe types of liver diseases, including hepatocellular carcinoma. Furthermore, deletions or insertions affecting the C-terminal region of HBx may also contribute to the severity of the clinical outcome in chronic patients. In addition, our recent study indicated that a novel mutation type (X8Del) composed of an 8-bp deletion in the C-terminal region of the HBx could contribute to occult HBV infection in vaccinated Korean individuals via a reduced secretion of HBsAg and virions. Therefore, several distinct types of HBx mutations may contribute to HBV pathogenesis by regulating HBV replication or host genes related to cell homeostasis.