Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers.

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the serum in absence of hepatitis B surface antigen (HBsAg). Studies were conducted to screen for occult HBV infection among family members of HBV carriers, incidentally detected positive for HBV infection with a view to assess the pattern of virus transmission among them. Nested PCR assay, employing independent sets of primers to surface and core genes, was used for detection of HBV DNA in serum samples from 28 index cases with asymptomatic HBV infection, and in serum samples from 72 HBsAg negative/anti-HBc positive family members. HBV DNA was detected in 15 HBsAg negative family members of 10 HBsAg positive index patients and was studied in detail. Direct sequencing of S gene region of 25 isolates (10 index cases and 15 contacts) and phylogenetic analysis with data base sequences revealed that genotypes A, C, and D and subtype adw2, adr, and ayw3 were present among them. Evidence of transmission from outside family sources was found in addition to intrafamilial transmission among individuals with occult infection. Mutations in the major hydrophilic loop (MHL) of the S gene region were also detected, including the 'vaccine escape' mutation G145R in three cases. Although majority of the occult infection was associated with low viral load, 3/15 (20%) cases were with higher viral load and potential infectivity. These cases are especially notable in diagnostic, blood banking, and transplantation services.