Les antibiotiques sont produits sous des formes pharmaceutiques telles que des pilules acheter du zithromax
elles permettent d'injecter la quantité de préparation strictement nécessaire.
Hbv treatment and pregnancy
HBV treatment and pregnancy
Liver Unit, IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St. Georg Hamburg, Germany
See Article, pages MS
The management of hepatitis B virus (HBV) infection in preg-
often results in clinical remission This scenario is in contrast
nancy is complex. Because infection with HBV in infancy often
to the oral antiviral agents that generally require long-term ther-
leads to chronic disease, prevention of perinatal or vertical trans-
apy and result in lower rates of stable HBeAg seroconversion and
mission is a major goal. Worldwide, vertical transmission
some HBsAg loss only in HBeAg positive patients For those
remains the most frequent route of infection, particularly in
who require therapy, it is advisable to discuss the issue of preg-
endemic areas where up to 20% of women of childbearing age
nancy before starting the treatment.
may have HBV. These women constitute a reservoir for perinatal
No antiviral agent has been approved for use in pregnancy.
transmission, which is associated with a very high rate of chro-
Thus, when a woman on HBV antiviral therapy becomes preg-
nicity . Without immunoprophylaxis, up to 90% of infants
nant, a decision needs to be made whether she should continue
born to hepatitis B e antigen (HBeAg)-positive mothers become
therapy for the duration of the pregnancy or if therapy should
HBV chronically infected. However, the maternal screening pro-
be withdrawn immediately. As with all decisions during preg-
grams and universal vaccination in newborns with active and
nancy, the health of the mother and the fetus must be considered
passive immunoprophylaxis have dramatically reduced HBV
independently. From the perspective of the fetus, the major con-
transmission rates. But even with the use of appropriate prophy-
cern is the risk of exposure to medication during early embryo-
laxis with HBV immunoglobulin (HBIG) and HBV vaccination, a
genesis. From the perspective of the mother, the major issue is
signiﬁcant risk of vertical transmission remains, particularly in
whether stopping or switching medication will adversely affect
mothers with high viral loads and positive hepatitis B e antigen
both short- and long-term liver disease outcomes. In general, if
(HBeAg) status. In one series of mothers with high viral loads, this
the mother is known to have signiﬁcant ﬁbrosis, therapy should
risk was as high as 28% . An HBV DNA level greater than
be continued because the risk of ﬂare with withdrawal of therapy
107 copies/ml is an important risk factor for HBV transmission
could result in reactivation and even decompensation of her liver
Wiseman et al. recently studied 298 chronically HBV-
disease. This effect on the mother's health could also impact the
infected women and their infants, who were vaccinated and
health of the fetus.
who received HBIG. The infants were tested for HBV at 9 months
Decisions about initiating therapy during pregnancy again
of age and showed an HBV rate of 8.5% born to mothers with
must include consideration of the risks and beneﬁts for the
virus levels greater than 8 log10 copies/ml. There is no indication
mother and the fetus; furthermore, in which trimester the ther-
to perform a caesarian section to reduce HBV transmission if vac-
apy should be started must be considered, too. Interferon has
cination and HBIG are administered accordingly.
antiproliferative actions and is contraindicated during pregnancy.
Factors that inﬂuence treatment choices in women of child-
Furthermore, all polymerase inhibitors interfere with the replica-
bearing age include safety in pregnancy and breastfeeding, efﬁ-
tion of mitochondrial DNA, and this can result in mitochondrial
cacy of the agent, its barrier to resistance, length of therapy,
toxicity leading to the lactic acidosis syndrome Although
and most important, the cause of treatment, i.e. treating the
lactic acidosis syndrome is very uncommon in adults, less is
mother because of an advanced liver disease or treating the
known about the potential ramiﬁcations of mitochondrial toxic-
unborn child to prevent transmission.
ity in the developing fetus. These effects may be more diverse,
If pregnancy is contemplated in near future, it may be prudent
because toxicity may affect organogenesis.
to delay therapy until after the child is born. This approach
Of the nucleoside and nucleotide analogs indicated for the
requires a careful assessment of the degree of hepatic activity
treatment of chronic HBV infection, all are classiﬁed as Food
and ﬁbrosis. Although it is not to be used in the pregnant woman,
and Drug Administration (FDA) pregnancy risk category C except
interferon can be used in the woman of childbearing age, because
for tenofovir and telbivudine, which are category B. Most human
therapy with this agent is for a deﬁned period of 48 weeks and
experience with antiviral drug therapy in pregnancy has beenwith lamivudine. More than 4600 women have been exposed tothe drug during their second or third trimester and reported
⇑ Address: IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St. Georg
to the Antiretroviral Pregnancy Registry (APR). The APR monitors
Hamburg, Lohmuhlenstrasse 5, D-20099 Hamburg, Germany. Tel.: + 49 40
the safety of antiretroviral agents in the United States of pregnant
181885 3796; fax: + 49 40 181885 3788.
women who have been exposed to lamivudine, tenofovir,
Journal of Hepatology 2011 vol. xxx j xxx–xxx
emtricitabine, or other antiviral drugs. Despite the large number
number of pregnant HBsAg positive women. The disadvantages
of enrolled patients and reassuring results showing no signiﬁcant
are the short follow up, only seven months after delivery, and
increase in birth defects, there are limitations, including short fol-
the lack of results of virologic breakthrough and resistance data.
low-up and recording only defects identiﬁed at birth. Develop-
Furthermore, it is not a randomized study, patients were allo-
mental anomalies (e.g. cardiac or neurologic defects) identiﬁed
cated depending on their own wishes and prophylaxis was
at a later date may therefore be omitted. Similar registries spon-
started either during the second trimester or during the third tri-
sored by the pharmaceutical industry have been severely limited
mester but without a deﬁnitive time point. It is unclear whether
by poor enrollment and provide little meaningful data. For the
mothers with high levels of viremia started earlier compared to
APR, no signiﬁcant difference was reported in the rate of adverse
those with low levels of viremia. The risk of HBV transmission
outcomes if the initial exposure of any HBV drug was in the ﬁrst
could have been analyzed even better in relation to the time of
trimester (2.7%) compared to the second or third trimester (2.5%)
starting prophylaxis in addition to HBV DNA levels. The primary
of pregnancy or compared to a non HIV nontreated general
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 fol-
Even though lamivudine is classiﬁed as FDA pregnancy risk cat-
low-up to analyze HBV perinatal transmission, at least newborns
egory C, it is associated with the risk of birth defects that is not
should be followed for 1 year. Nevertheless, this study is adding
higher than the baseline birth defect rate. A meta-analysis of 10
very important information to our very limited knowledge of
randomized clinical trials (RCTs) examining 951 HBV carrier moth-
safety of polymerase inhibitors in pregnant women and helps
ers was reported to evaluate the efﬁcacy of lamivudine in reducing
to support the ‘‘B'' rating of telbivudine.
in utero transmission of HBV . The RCTs evaluated included
Rather than switching agents, withdrawal of treatment for the
newborns who received immunoprophylaxis at birth and women
duration of pregnancy may be preferable in some cases, espe-
who were treated with lamivudine from 24 to 32 weeks of gesta-
cially to the mother who wants to avoid any potential future risk
tion, until delivery to 1 month post-delivery. Newborns in the lam-
to the fetus. What would be the consequence to the mother of
ivudine group had a 13–24% signiﬁcantly lower incidence of
stopping treatment completely? The natural history of chronic
intrauterine exposure and a lower perinatal infection rate at 9–
HBV in pregnancy has not been well described. Limited data exist
12 months. This report was limited by the quality of the studies
to suggest that, rarely, severe complications of HBV occur late in
included. On the other hand, in a recent poster presented at EASL
pregnancy, with reports of liver failure in previously asymptom-
2011 in Berlin Ayres et al. showed that although the therapy
atic individuals . Data speciﬁcally addressing the risk of stop-
with lamivudine achieved an HBV DNA load reduction of
ping therapy during pregnancy are only anecdotal.
3 log10 IU/ml, in 20% of the pregnant women, the viral load
Overall, it appears that the risk of an adverse outcome with
remained high (>1 107 IU/ml) and resistant mutations were
continuing antiviral therapy during pregnancy is likely to be very
detectable only after three months of therapy, calling for more
low. However, therapy could be discontinued with close observa-
potent antiviral drugs to be used to prevent transmission.
tion of the mother to avoid continued fetal exposure during the
Of the two agents classiﬁed as FDA pregnancy risk category B,
ﬁrst trimester, especially in the patient who does not have
only tenofovir received this classiﬁcation based on the data col-
lected in human exposure, so far. There have been no other pub-
When deciding on starting therapy in the third trimester, the
lished studies using entecavir, adefovir, or emtricitabine for
perinatal transmission outcome of prior pregnancies should be
preventing HBV vertical transmission, and these drugs should
considered. If previous pregnancies did not result in perinatal
be switched immediately, if a woman becomes pregnant.
transmission, then a viral load of greater than 107 copies/ml
The experience with tenofovir in pregnant women consists of
should be used to determine if therapy should be initiated (sim-
606 women in their ﬁrst trimester and 336 in their second trimes-
ilar to women who had no children). However, if perinatal trans-
ter from the APR. The rate of birth defects associated with tenofovir
mission did occur with a prior pregnancy, then the risk of
ranges from 1.5% (second-trimester use) to 2.3% (ﬁrst-trimester
perinatal transmission in the current pregnancy is likely higher.
use), which is again similar to the background rate. Telbivudine
In such cases, strong consideration for initiating therapy in the
received its pregnancy risk category B rating based on animal stud-
third trimester is recommended, regardless of the mother's viral
ies; there were few human pregnancy registry data up to now.
load at the end of the second trimester.
In this issue of the Journal of Hepatology, Han et al. present a
Despite the position from the American Academy of Pediatrics
prospective study that evaluates the efﬁcacy of telbivudine
stating that breastfeeding is not contraindicated in naïve women
for preventing HBV newborn infection performed in 230 preg-
with HBV if HBIG and vaccination have been administered
nant HBsAg positive patients with HBV DNA levels of
accordingly for mothers on antiviral therapy, breastfeeding
>1.0 106 copies/ml. The study shows that telbivudine plus vac-
cannot be recommended. According to prescribing information,
cination is superior to HBIG and HBV vaccines only in newborns
it has not been recommended that women breastfeed their
to prevent HBV transmission (0% vs. 8%). This study reconﬁrms
infants while taking lamivudine or tenofovir, to avoid risking
data from a recent study of 31 pregnant women in China, treated
postnatal transmission of HIV-1 infection (package inserts lami-
with telbivudine started at weeks 28–32 of pregnancy and con-
vudine and tenofovir). Although it is known that lamivudine
tinued to 30 days postpartum All babies received active
and tenofovir are both excreted into human breast milk, little is
and passive immunoprophylaxis. The infection rate was 0% in
known about the extent of exposure of antiviral agents during
those treated with telbivudine and 13.3% in the untreated
breastfeeding. Thus, little is known about the overall safety of
breastfeeding in this setting.
The advantages of the study by Han et al. are the use of tel-
In summary, treatment of HBV infection during pregnancy
bivudine, a more potent antiviral drug than lamivudine with a
remains a challenge, the risks and beneﬁts must be weighed care-
lower risk of HBV drug resistance and the inclusion of a large
fully and there are still numerous gaps in our knowledge. The
Journal of Hepatology 2011 vol. xxx j xxx–xxx
JOURNAL OF HEPATOLOGY
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The Neurobehavioral Pharmacology of Ketamine: Implications for Drug Abuse, Addiction, and Psychiatric Disorders Keith A. Trujillo, Monique L. Smith, Brian Sullivan, Colleen Y. Heller, Cynthia Garcia, and Melvin Bates Ketamine was initially developed in the 1960s as a safer alternative to phencyclidine (PCP1) for anes- Ketamine was developed in the early 1960s as an anesthetic
Juluri et al. BMC Gastroenterology 2011, 11:38http://www.biomedcentral.com/1471-230X/11/38 Polyethylene glycol vs. sodium phosphate forbowel preparation: A treatment arm meta-analysis of randomized controlled trials Ravi Juluri1*, George Eckert2 and Thomas F Imperiale3,4,5 Background: Results of meta-analyses of randomized trials comparing PEG and NaP are inconsistent and have notincluded trials comparing either or both preps to less traditional ones.AIM: To perform a meta-analysis by treatment arm.