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Qu et al. Etiological prevention of liver cancer

Telbivudine and tenofovir are both classified as different, antiviral therapy for pregnant women with high
pregnancy Category B drugs. A large prospective, HBV DNA levels is recommended in various guidelines
controlled trial included 229 HBeAg-positive patients including the AASLD, EASL and APASL. A long term
with HBV DNA levels > 7 log10 copies/mL found that follow-up should be conducted regarding the safety of
the telbivudine given to 135 pregnant women from the mothers and/or their infants. This work was funded
weeks 20 to 32 of gestation safely reduce perinatal HBV by the State Key Projects Specialized on Infection
transmission compared to the 94 untreated pregnant Diseases of the Thirteenth 5-year Plan of China.
women. MTCT was markedly lower in the treatment
group (0% vs. 8%) and the immunized infant had a Status of immunological memory after
higher proportion of detectable HBsAb (100% vs. 92%). neonatal vaccination in young adults
A short-term follow-up showed that telbivudine was In children, HBV vaccination proves to be very efficacious
well-tolerated with no safety concerns in the mothers in decreasing HBsAg seroprevalence [23,25,27,28,33,58] . After
and/or their infants [72] . 10-15 years of the vaccination, neutralizing antibodies
(anti-HBs) waned or reached undetectable levels in
Tenofovir Disoproxil Fumarate (TDF) currently remains many individuals, and some became seropositive with
the first-line therapy for chronic HBV infection based on anti-HBV core antigen (anti-HBc) [75,76] . Although HBV
its safety and resistance profile as well as its potency primary infection in the perinatal period and early life
and efficacy. It is currently rated as pregnancy Category has a high rate of chronicity, the possibility of becoming
B. To evaluate the efficacy and safety of maternal TDF chronically infected in unprotected young adulthood
in reducing HBV MTCT, a prospective, multi-center was reported to be about 2.7-7.7% after horizontal
trial was conducted that enrolled 118 HBsAg-positive transmission [12,14,77] . It is necessary to confirm the
and HBeAg-positive pregnant women with HBV DNA efficacy of neonatal vaccination in protecting young
≥ 7.5 log10 IU/mL. In this trial, 56 mothers received adults who later had low or absent levels of anti-HBs.
no medication and 62 mothers received TDF 300
mg daily from 30-32 weeks of gestation until 1 month In order to understand the long-lasting immunity in
postpartum, respectively. Treatment with TDF for highly preventing chronic HBV infection, Zanetti and colleagues
viremic mothers decreased infant HBV DNA at birth and introduced a booster test to assess the presence of
infant HBsAg positivity at 6 months. However, TDF did anamnestic responses against HBV infection based on
not affect the MTCT rate in the per-protocol analysis at the principle that re-exposure of HBsAg in recombinant
the 12-month follow-up [73] . To verify the effect and safety vaccine should mimic the response to wildtype HBV
[78]
of TDF, the China Study Group for the Mother-to-Child infection . The enrolled population in this study
consisted of children born to HBsAg-negative mothers
Transmission of Hepatitis B included 200 mothers who and vaccinated adolescents (Air Force recruits), who
were positive for HBeAg and had an HBV DNA level were all vaccinated 10 years before the enrollment.
higher than 200,000 IU/mL (ClinicalTrials.gov number Serum anti-HBs levels of each individual was firstly
NCT01488526) [74] . The participants were randomly quantified, followed by giving 10 μg recombinant HBV
assigned in a 1:1 ratio to receive usual care without vaccine if they were seronegative for anti-HBc. Serum
antiviral therapy or to receive TDF from 30 to 32 weeks anti-HBs level in each of the participants was quantified
of gestation until postpartum week 4. At delivery, 68% of again two weeks later. Presence of an anamnestic
the mothers in the TDF group (66 of 97 women) had an response was defined as those with prebooster anti-
HBV DNA level < 200,000 IU/mL, while only 2% of the HBs titers < 10 mIU/mL and post-booster titers ≥ 10
mothers had an HBV DNA level < 200,000 IU/mL in the mIU/mL, a representation of protection conferred
control group. The TDF effect in reducing mothers’ HBV through immunologic memory. Later studies that used
DNA level was significant (P < 0.001). All the infants similar or modified methods, which also determined the
received immunoprophylaxis. At postpartum week 28, presence of HBsAg-specific T cells, were conducted in
the MTCT rate was found to be significantly lower in the many different populations worldwide [79] . These results
TDF group than in the control group, both in the intention- revealed that HBV vaccine does elicit immunologic
to-treat analysis [with transmission of virus to 5% of the memory, in which memory B cells could appropriately
infants (5 of 97) vs. 18% (18 of 100), P = 0.007] and the generate a robust anamnestic response to HBsAg even
per-protocol analysis [with transmission of virus to 0 vs. if the anti-HBs titer falls below 10 mIU/mL.
7% (6 of 88), P = 0.01]. Notably, there was no significant
difference in the fetal safety profiles between the two Nevertheless, the conclusion is controversial regarding
groups [75] . The results indicated that it might be too late the immune protection of the uninfected children/
to prevent the MTCT to commence the TDF treatment adolescents who had serum anti-HBs < 10 mIU/mL,
at 30 to 32 weeks of gestation if the pregnant women based on the studies conducted in the vaccinated
had higher viremic HBV [73] . As the participants were population who lived in areas with different HBV

234 Hepatoma Research ¦ Volume 3 ¦ October 25, 2017