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Qu et al. Etiological prevention of liver cancer

a recommendation/guideline of HBV vaccination in = 1.88, 95% CI: 1.07-3.30) and detectable HBV DNA
children in December 2016 (http://www.nhfpc.gov.cn/jkj/ in the cord blood (OR = 39.67, 95% CI: 14.22-110.64)
s3581/201701/a91fa2f3f9264cc186e1dee4b1f24084. are independent risk factors for immunoprophylaxis
shtml). For general infants, it recommends three doses failure [65] . Maternal HBV-DNA level > 6 log10 copies/mL
of HBV vaccines, with the first dose vaccine to be given (200,000 IU/mL) in Chinese women is still associated
within 24 h after delivery. The second and third doses are with the risk of immunoprophylaxis failure [65] .
to be given at 1 month and 6 months of age. Each dose
contains 10 μg vaccine from recombinant yeast or from Treatments aimed at lowering HBV-DNA levels during
Chinese hamster oocyte. For infants born to HBsAg- pregnancy may be helpful to ultimately decrease global
positive mothers, it recommends the administration of disease burden. The exact threshold for treatment
100 IU HBIG within 12 h after birth combined with a full remains controversial. However most studies have
course of HBV vaccination. The administration dose is accepted levels greater than 200,000 IU/mL as
10 μg vaccine from recombinant yeast or 20 μg vaccine significant viremia [69] . A Systematic Review and Meta-
from Chinese hamster oocyte. The vaccinated infants Analysis found that the use of any antiviral therapy
should be tested for the presence of HBsAg and the compared to control reduced the MTCT risk as defined
anti-HBs titer 1-2 months after completing the third by infant HBsAg seropositivity (RR = 0.3; 95% CI: 0.2-
dose of vaccine. If he/she is seronegative for HBsAg 0.4) or infant HBV-DNA seropositivity (RR = 0.3; 95%
and has anti-HBs < 10 mIU/mL, the fourth dose of HBV CI: 0.2-0.5) at 6-12 months. Notably, no significant
vaccine should be given. If the neonates are born to differences were found in congenital malformation rate,
HBsAg-positive mothers at premature gestation ages or prematurity rate, and Apgar scores [70] .
low birth weights, the first dose of the vaccine should be
administered when they are one month old. Lamivudine has been used the longest as antiviral
therapy of chronic HBV approved by the Chinese Food
Anti-viral therapy and vaccination for and Drug Administration, and is currently classified as
prevention of mother-to-child transmission a pregnancy Category C drug. A meta-analysis and
Despite the increased efficacy of passive-active systematic review of 14 lamivudine studies showed that
immunization given to infants born to HBsAg-positive lamivudine reduced maternal HBV DNA levels, reduced
mothers, some infants still become infected with infant HBsAg seropositivity by 11.7% and reduced infant
HBV, especially those born to HBeAg-positive and HBV DNA seropositivity by 21.2%, respectively [70] . During
highly viremic mothers [59] . Many different studies have the period of January 2009 to March 2011, a prospective,
identified that mothers with significant viremia are at open-label, interventional trial was conducted in Beijing
a much higher risk of MTCT. HBV can be vertically Youan Hospital of China (ClinicalTrials.gov Number:
transmitted to their infants, indicated by HBV-DNA NCT01743079). In the enrolled 700 pregnant women
positivity in the cord blood [64,65] . Experience in who were HBsAg-positive and HBeAg positivity, with
reducing the risk of perinatal transmission of human HBV-DNA levels > 6 log10 copies/mL (200,000 IU/mL),
immunodeficiency virus with lamivudine-zidovudine and alanine aminotransferase (ALT) < 40 IU/mL, 55
combination therapy drove the physicians to follow a women were treated with lamivudine, 263 were treated
similar rationale to prevent the perinatal transmission with telbivudine, and the rest (374 women) received no
of HBV-infection. Lamivudine, which strongly inhibits antiviral therapy (the control group). Based on the data
HBV replication, was used to treat eight highly from 661 infants who completed the HBV vaccination
viraemic HBV-positive Caucasian or Negroid pregnant series and the 52-week follow-up, the study found
women (HBV-DNA levels ≥ 1.2 × 10 geq/mL) starting that mothers who received lamivudine or telbivudine
9
from week 34. The results suggest that reduction had significantly lower HBV DNA levels than those
of viremia by antiviral therapy may be an effective who received no antiviral therapy. At birth, HBsAg
and safe measure to reduce the risk of MTCT [66] . was detected in 20% of treated and 24% of untreated
Therefore, several studies were conducted to evaluate newborns; however, by week 52, an intention-to-treat
the risk of MTCT with different maternal levels of HBV analysis indicated 2.2% (95% CI: 0.6-3.8) of HBsAg-
DNA. Many studies have identified that serum HBV positive infants from the treated versus 7.6% (95% CI:
DNA level in pregnant women was the single most 4.9-10.3) in the untreated group (P = 0.001), and no
important predictor and independent risk factor for difference in HBsAg-positive rate between infants in the
immunoprophylaxis failure in different populations [59,65] . lamivudine or telbivudine groups. On-treatment analysis
Some studies reported that maternal HBV DNA level indicated 0% of HBsAg-positive infants in the treated
of > 8 log10 IU/mL was associated with increased group versus 2.84% in the untreated group (P = 0.002).
likelihood of immunoprophylaxis failure [67,68] . A large The study concluded that lamivudine or telbivudine in
scale study on more than 1000 Chinese mother- late pregnancy for highly viremic mothers was equally
infant pairs found that maternal HBV DNA levels (OR effective in reducing MTCT .
[71]
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