Received: April 21, 2015
Accepted: May 11, 2015
Mediterr J Hematol Infect Dis 2015, 7(1): e2015042, DOI 10.4084/MJHID.2015.042
This article is available on PDF format at:
A Montoya-Ferrer1,2*, AM Zorrilla1,3, J Viljoen1,4, JP Molès1, ML Newell4,5, P Van de Perre1,6 and E Tuaillon1,6
1 Université Montpellier 1, Inserm U1058, UM1 UFR Pharmacie, 15 avenue Charles Flahault, 34090, Montpellier, France
2
Département des Maladies Infectieuses et Tropicales, UMI 233, Centre
Hospitalier Régional Universitaire de Montpellier, 80 av Augustin
Fliche - 34295 Montpellier, France
3 University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, Florida 32603, United States
4
Africa Centre for Health and Population Studies, University of
KwaZulu-Natal, R618 en route to Hlabisa, Somkhele, A2074 Rd, Mtubatuba
3935, Durban, South Africa
5 Faculty of Medicine,
University of Southampton, Mailpoint 887, Institute of Developmental
Sciences Building, Southampton General Hospital, Tremona Road,
Southampton, Hants SO16 6YD, United Kingdom
6 Département
de Bactériologie-Virologie, Centre Hospitalier Universitaire de
Montpellier, 191 Avenue Doyen Giraud, Montpellier, 34295, France.
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Dear Editor
Breastfeeding
is recommended by the World Health Organization regardless of mother’s
hepatitis B virus (HBV) status since breast milk is not considered as
an efficient pathway for HBV perinatal transmission.[1]
However, concerns about a possible risk of HBV transmission through
breastfeeding arises under conditions favoring an increase of HBV DNA
viral load in breast milk, particularly among unvaccinated children.[2,3]
We
present here a case of an HIV-HBV co-infected mother who exposed her
child to a significant HBV infectious inoculum via breast milk, likely
due to a hepatitis flare or an acute HBV infection.
The
mother-child couple was enrolled in the Kesho Bora study; a randomized
controlled trial evaluating maternal prophylactic strategies to reduce
HIV transmission through breastfeeding.[4] At week 6
post-delivery, a > ten fold elevation of alanine transaminase (ALT:
750 IU/L) was observed in a 20 years old mother. This mother was
included in the control arm receiving short course antenatal zidovudine
and single-dose intrapartum nevirapine in accordance with per national
guidelines at the time. Serological testing confirmed HBV infection
(positivity for HBsAg) and ruled out hepatitis A and C infections.
Serum and breast milk samples were retrospectively assessed for for HBV
DNA levels at week 2 at week 2 and 12 using a standardized qPCR method
(HBV Generic PCR, Omunis, Montpellier, France). Significant levels of
HBV DNA were found in both left and right breast milk samples at week 2
post-delivery (> 103 log10 HBV DNA IU/mL) whereas, ALT level was normal (12 IU/ml). HBsAg levels were also quantified in breast milk (>101
IU/ml) using a quantitative assay (Architect HBsAg QT assay, Abbott,
Chicago, IL). A dramatic decrease in the levels of HBV DNA and HBsAg
was observed in both serum and breast milk at week 12 post-delivery (Table 1).
Serum and breast milk became negative for HBsAg 6 months after delivery
without detection of anti-HBs antibody. The newborn was infected
neither by HIV nor by HBV despite a vaccine schedule starting at week
6. Protective anti-HBs titers were observed in response to HBV
vaccination (>ten mIU/mL) at month 12. We estimate that the
intestinal mucosa of the infant was in contact with more than one
million HBV particles/per day based on a daily consumption of 300 ml
during the first weeks of life. Although HBV infection is a major
health concern worldwide, very few studies have explored HBV DNA in
breast milk.
 |
Table 1 |
HBV DNA has been detected in the colostrum of mothers tested positive for HBe antigen using PCR and Southern blot hybridization[5] and in banked human milk samples using a nested PCR.[6]
Recently,
HBV DNA was tested in serum and breast milk using a standardized
quantitative PCR method in HIV-HBV coinfected mothers who were under
lamivudine-containing antiretroviral regimen from the 25th week of pregnancy.[7] At delivery, 11/26 (42%) women had significant HBV DNA levels in serum (ranging from 3.3 to >8 log10 IU/mL) that steadily decreased at months 1, 3, and 6 postpartum (median of 5.2, 4.5 and 2.8 log10
IU/mL respectively). HBV DNA was detected in breast milk from three HBV
viremic women (33%) and four out of 24 breast milk samples (17%). When
detectable, HBV DNA levels in breast milk were low in all cases ranging
from 1.18 to 2.20 log10 IU/ml, suggesting that level of HBV DNA in
breast milk might always be negligible. The rate of HBV infection was
also assessed among 23 HIV-HBV exposed children along the two years
study period. Diagnosis of transient HBV infection was made in four
children whereas other three children acquired HBV infection during the
postnatal period (first HBsAg positive test at 12 months in one
case and 24 months in the other two cases). Pirillo et al observed that
those 7 children were exposed to the highest HBV infectious inoculum,
not only at delivery, but also during all the postnatal period, since
their mothers presented the highest levels of HBV DNA in serum.
However, no correlation was found between HBsAg positivity and HBV DNA
levels in breast milk.
In our case, exposure to a larger
amount of HBV infectious particles via breast milk was detected, but
the child, who was correctly vaccinated, was not infected with HBV.
This result seems to confirm that breastfeeding is not an effective
route of HBV transmission during the perinatal period, as previously
reported in clinical studies.[2,3] However, in
contrast with the results of Pirillo et al, our data show that HBV
exposition via breast milk could be significant, especially during a
high HBV replicative phase. HBV exacerbations or hepatitis flares often
occur among chronic HBV infected mothers after pregnancy leading to
higher levels of HBV replication in the blood[8,9]. In
our case, an accurate differential diagnosis between an acute HBV
infection and a hepatitis flare could not be made since the time of HBV
infection was unknown. A typical elevation of ALT 6 to 10 weeks after
delivery preceding the upsurge of HBV DNA levels suggested a hepatitis
flare.[10] However, this mother also experienced HBsAg clearance within six months, as often occurs in acute HBV infections.[11]
Hepatitis
flares or acute HBV infections in chronic HBV infected patients do not
usually required antiviral treatment since most of the episodes resolve
spontaneously.[12] In pregnant women, the risk of
fulminant or severe hepatitis following hepatitis flares or acute HBV
infections does not appear increased.[9] However, as
in general population, those episodes may progress to a fulminant liver
failure and must be treated with nucleot(s)ide analogs and be evaluated
for liver transplantation.[12,13] Due to its safety
and better resistance profile, Tenofovir is currently the antiviral of
choice for the treatment of severe acute HBV infection, and its
efficacy has been demonstrated even in cases in which previous
nucleoside analog treatment as lamivudine had failed.[14] Hence, Tenofovir provides a better efficiency during a hepatitis flare or a post-delivery acute HBV infection.
Exposure
to a significant HBV infectious inoculum through breastfeeding should
not always be considered negligible in children from HIV-HBV coinfected
mothers who do not receive any active antiviral treatment against HBV.
However, cumulative exposure during lactation does not seem to
contraindicate breastfeeding among correctly vaccinated children
despite the immaturity of their intestinal mucosa.
Acknowledgements
We acknowledge the Kesho
Bora study team in Burkina Faso, South Africa, and Kenya and all
participating pregnant women and babies.
.
References
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