The clinical significance of surface antigen variants of hepatitis B virus

Abstract

Hepatitis B surface antigen (HBsAg) is not only critical to the biology of hepatitis B virus (HBV), it is also the basis of the currently available vaccines, assays to detect it in serum are crucial for diagnosis of infection and antibodies against it are used clinically to suppress infection of transplanted livers. All of these rely on antigenic interactions between HBsAg and HBsAb. Thus, it should not be surprise that changes in epitopes will affect all these situations. It is useful to classify such changes simplistically as variants, found in natural isolates, and mutants, which are observed to emerge, usually under immunological pressure, often medical in origin. The former tend to affect the sensitivity of diagnostic assays and the latter allow escape of viruses in vaccinees and those being treated with HBsAb. The majority of these changes cluster in the hydrophilic central core of HBsAg, from aa99 up to 169. They are gaining importance as causes of mistaken diagnosis and are associated with infection of vaccinees and transplanted livers. There is a danger that they will become the dominant strains as vaccination becomes universal. More data are required on the epidemiology and antigenicity of these changes.

Characterization of a Hepatitis B virus strain in southwestern Paraná, Brazil, presenting mutations previously associated with anti-HBs Resistance

“…Although the amino acids found at positions 115 (T), 116 (T) and 129 (Q) are considered to be conserved residues and amino acids located at positions 105 (P/HAS) and 140 (T/S) are non-conserved residues (SCHAEFER et al 2005), the presence of a P at position 105, three T's at positions 115, 116 and 140 and a Q at position 129 observed in the present study have been associated with monoclonal or polyclonal therapy with anti-HBs after liver transplantation, with these mutations tending to accumulate within and around the HBs2 and HBs4 regions 6,7,8,25,32 . Although mutation T114R has also been associated with monoclonal or polyclonal anti-HBs therapy after liver transplantation, a serine (S) was found at this position, which is a neutral polar amino acid like threonine (T).…”

Occult hepatitis B virus infection in immunocompromised patients

“…A number of explanations for the persistence of HBV DNA in HBS-negative samples have been proposed, including HBV DNA in low copy numbers [27], genetic variations of the S gene [30,31], and immune complexes in which HBsAg is hidden [32].…”

Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under hbig immunoglobulin after liver transplantation

“…Only 1 patient (NR21) selected a mutation (P120T) on FCV, which has been associated with failure of HBIg prophylaxis. [29][30][31][32][33] However, 1 nonresponder (NR24) reverted this mutation P120T on FCV.…”

“…From previous studies, we know that certain amino acid changes are associated with failure of HBIg immunoprophylaxis. [29][30][31][32][33] Before the start of nucleoside analogue therapy, 8 patients (PR11, NR22, NR24, R01, R02, PR16, PR19, NR26) (Tables 11, 12, and 13) also showed such mutations within the S-gene. These mutations were a G145R mutation associated with a D144E mutation of the HBsAg corresponding to a W501E mutant of the HBV-DNA polymerase in 2 patients (R01, NR22), and a P120T mutation corresponding to a T476N mutation of the HBV-DNA polymerase in 6 (R01, PR11, NR24, PR 16, PR19, NR26), of whom 1 (R01) also had the G145R and D144E mutations.…”