Is mother-to-infant transmission the most important factor for persistent HBV infection?

Abstract

Of the infants born to hepatitis B surface antigen (HBsAg)-positive mothers globally, 42.1% who did not receive hepatitis B virus (HBV) passive-active immunoprophylaxis and 2.9% of infants who received the immunoprophylaxis acquired HBV infection perinatally. Moreover, perinatal infection occurred in 84.2% (18.8%–100%) and 8.7% (0.0–21.0%) of infants born to hepatitis B e-antigen (HBeAg)-positive mothers who did not and did receive immunoprophylaxis, respectively; by contrast, the infection rates were 6.7% (0.0–15.4%) and 0.4% (0.0–2.5%) for infants born to HBeAg-negative-carrier mothers, respectively. The chronicity rates of HBV infection acquired perinatally were 28.2% (17.4%–33.9%) in infants born to HBeAg-negative mothers and 64.5% (53.5%–100%) in infants born to HBeAg-positive mothers. HBV mother-to-child transmission was more frequent in East Asia relative to other areas. In addition to differences in the endemic HBV genotype, the interchange of allelic dominance in genetic polymorphisms in HLA class II and NF-κB between the Chinese and European populations may explain why chronic HBV infection frequently affects the Chinese. The risk of progressing into chronic infection was inversely related to the age of children at the time of horizontal transmission. To further diminish HBV chronic infection, it is necessary to enforce antiviral treatment after the 28th week of gestation for HBeAg-positive mothers and to improve the health habits of carrier mothers and household sanitary conditions.

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

“…The polymorphic genotypes that are significantly association with increased risks of chronic progression of HBV infection as well as immune selection of the end-stage liver diseases-associated HBV mutations are more frequent in the Han Chinese than in European populations. These data indicate that the Han Chinese are inherently more apt to progressing into chronic infection once exposed to HBV infection than European, whereas European tend to recover from HBV infection spontaneously [12] . This might be one of the reasons why chronic HBV infection and the HBVinduced end-stage liver diseases are more frequent in Chinese than in European populations.…”

“…Several longitudinal studies carried in China have also demonstrated that baseline A1762T/G1764A mutation increases the risk of HCC in chronic HBV carriers or CHB patients [34][35][36][37] . Among the HCC-risk HBV mutations, the A1762T/G1764A is usually detected in the early stage in young adolescents, while other mutations including T1753V, C1653T, G1899A, and preS deletion appear only at the late stage of chronic HBV infection [12,38] . Reaction to chronic HBV infection, as characterized by immune response-induced hepatocyte damage and release of transaminase, facilitates the generation of the HBV mutations, indicating active immune selection of the HBV mutants during HBeAg seroconversion from HBeAg-positive to HBeAg-negative.…”

“…The infection rates were 6.7% and 0.4% for infants born to HBeAgnegative-carrier mothers, respectively. Moreover, the chronicity rates of HBV infection acquired perinatally were 28.2% in infants born to HBeAg-negative mothers and 64.5% in infants born to HBeAg-positive mothers [12] . This is possible due to the fact that the immaturity of immune system in infants make it unable to recognize HBV as an external antigen, thus establishing chronic HBV infection although the immune response can be aroused thereafter.…”

“…Interestingly, different human races have different allelic frequencies of SNPs that affect the expression of HLA-DP, HLA-DQ, and the inhibitory component of NF-κB complex IκBa gene NFKBIA. These genetic loci whose dominant alleles are significantly association with increased risks of chronic progression of HBV infection (or whose rare alleles are significantly associated with decreased risks of chronic HBV infection) include rs3138053 (affecting NFKBIA), rs2856718, rs7453920, and rs9275319 (affecting HLA-DQ), and rs9277378, rs2395309, rs2301220, and rs9277341 (affecting HLA-DP) [12] . The polymorphic genotypes that are significantly association with increased risks of chronic progression of HBV infection as well as immune selection of the end-stage liver diseases-associated HBV mutations are more frequent in the Han Chinese than in European populations.…”

Perinatal factors influencing mother-to-child HBV transmission

“…The exact mechanism by which HBV enters the fetus through the maternal placenta remains unclear. The HBsAg is detectable in amniotic fluid, cord blood, breast milk, vaginal fluid, and infant gastric contents, suggesting multiple routes for MTCT [4,5].…”