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[I have extracted some parts of the article. Please note, it is an Editorial, not a paper. Please consult your own doctors about treatment during pregnancy.][StephenW]
HBV treatment and pregnancy
Jörg Petersen
Liver Unit, IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St. Georg Hamburg, Germany
Editorial
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Even though lamivudine is classified as FDA pregnancy risk category C, it is associated with the risk of birth defects that is not higher than the baseline birth defect rate. A meta-analysis of 10 randomized clinical trials (RCTs) examining 951 HBV carrier mothers
was reported to evaluate the efficacy of lamivudine in reducing in utero transmission of HBV [12]. The RCTs evaluated included newborns who received immunoprophylaxis at birth and women who were treated with lamivudine from 24 to 32 weeks of gestation, until delivery to 1 month post-delivery. Newborns in the lamivudine group had a 13–24% significantly lower incidence of intrauterine exposure and a lower perinatal infection rate at 9–
12 months. This report was limited by the quality of the studies included. On the other hand, in a recent poster presented at EASL 2011 in Berlin [13], Ayres et al. showed that although the therapy with lamivudine achieved an HBV DNA load reduction of
3 log10 IU/ml, in 20% of the pregnant women, the viral load remained high (>1 107 IU/ml) and resistant mutations were detectable only after three months of therapy, calling for more potent antiviral drugs to be used to prevent transmission.
Of the two agents classified as FDA pregnancy risk category B,only tenofovir received this classification based on the data collected in human exposure, so far. There have been no other published studies using entecavir, adefovir, or emtricitabine for preventing HBV vertical transmission, and these drugs should be switched immediately, if a woman becomes pregnant. The experience with tenofovir in pregnant women consists of 606 women in their first trimester and 336 in their second trimester from the APR. The rate of birth defects associated with tenofovir ranges from 1.5% (second-trimester use) to 2.3% (first-trimester
use), which is again similar to the background rate. Telbivudine received its pregnancy risk category B rating based on animal studies; there were few human pregnancy registry data up to now. In this issue of the Journal of Hepatology, Han et al. present a prospective study [14] that evaluates the efficacy of telbivudine for preventing HBV newborn infection performed in 230 pregnant HBsAg positive patients with HBV DNA levels of >1.0 106
copies/ml. The study shows that telbivudine plus vaccination is superior to HBIG and HBV vaccines only in newborns to prevent HBV transmission (0% vs. 8%). This study reconfirms data from a recent study of 31 pregnant women in China, treated with telbivudine
started at weeks 28–32 of pregnancy and continued to 30 days postpartum [15]. All babies received active and passive immunoprophylaxis. The infection rate was 0% in those treated
with telbivudine and 13.3% in the untreated controls. The advantages of the study by Han et al. are the use of telbivudine, a more potent antiviral drug than lamivudine with a
lower risk of HBV drug resistance and the inclusion of a largenumber of pregnant HBsAg positive women. The disadvantages are the short follow up, only seven months after delivery, and the lack of results of virologic breakthrough and resistance data. Furthermore, it is not a randomized study, patients were allocated depending on their own wishes and prophylaxis was started either during the second trimester or during the third trimester
but without a definitive time point. It is unclear whether mothers with high levels of viremia started earlier compared to those with low levels of viremia. The risk of HBV transmission
could have been analyzed even better in relation to the time of starting prophylaxis in addition to HBV DNA levels. The primary end point of the study was defined as undetectable HBsAg and HBV DNA at birth and at month 7. This is a short period of follow-
up to analyze HBV perinatal transmission, at least newborns should be followed for 1 year. Nevertheless, this study is adding very important information to our very limited knowledge of safety of polymerase inhibitors in pregnant women and helps to support the ‘‘B’’ rating of telbivudine
..........
In summary, treatment of HBV infection during pregnancy remains a challenge, the risks and benefits must be weighed carefully and there are still numerous gaps in our knowledge. The benefits of treatment appear to be most pronounced in cases with high maternal viremia to prevent transmission and in mothers with advanced fibrosis to prevent flares. Viable treatment choices are limited to lamivudine, tenofovir, and telbivudine. Of these,
lamivudine and tenofovir appear to be the therapeutic options with reasonable human exposure and safety data in pregnancy and we do see now an increasing number of data for the safety of telbivudine, too.
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发表于 2011-11-21 20:23
