Published online Nov 28, 2015. doi: 10.4254/wjh.v7.i27.2729
Peer-review started: June 30, 2015
First decision: September 18, 2015
Revised: September 27, 2015
Accepted: November 13, 2015
Article in press: November 17, 2015
Published online: November 28, 2015
Hepatitis B virus (HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen (HBsAg) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBsAg, called the “a” determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBsAg detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBsAg mutants and their biological and clinical implications.
Core tip: Antibodies to the hepatitis B surface antigen (HBsAg) produced in response to hepatitis B virus infection or vaccination and those used in diagnostic assays to detect this antigen in serum are both directed against the ‘‘a’’ determinant region, common to all subtypes of the virus. Mutations occurring on the loops of the “a” determinant may be responsible for the lack of protection in immunized patients and in those individuals receiving hepatitis B immune globulin or for failed detection of HBsAg using commercial diagnostic assays. There is growing evidence in the last decade of the association between HBsAg mutations and the development of hepatocellular carcinoma (HCC), suggesting that the pre-S1 or pre-S2 large deletions are those prevalently associated with the development of HCC. This review article will focus on the clinical impact of the various HBsAg mutants.