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4/16/2022
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Hepatitis B in Pregnancy
Prof. Aboubakr elnashar
Benha university Hospital, Egypt
Aboubakr Elnashar
CONTENTS
1. EPIDEMIOLOGY& ETIOLOGY
2. DIAGNOSIS
1. Clinical
2. outcome
3. lab markers
3. TRANSMISSION
4. HEPATITIS & PREGNANCY
1. impact on pregnancy
2. impact of pregnancy
5. MANAGEMENT
1. Pre conceptional
2. Antenatal:
1. hbv-infected women who desire pregnancy
2. How to minimize the risk of transmission ?
3. Labour: mode of delivery
4. Postpartum:
1. breast feeding
2. Maternal follow up
3. Infant follow up
5. ALGORITHM
6. TAKE HOME MESSAGE Aboubakr Elnashar
1. EPIDEMIOLOGY & ETIOLOGY
Prevalence: 3.5% Africa: 6.1%
Of the 400 million individuals with chronic HBV worldwide:
50% acquired their infections perinatally.
 90% of infected infants will become ch carriers
2nd carcinogens after tobacco (WHO)
In Egypt: The prevalence rate of HBV (1.3%-1.5%) has
declined after national infantile immunization.
Gish RG and AC Gadano. J Vir Hep. 2006.
Aboubakr Elnashar Aboubakr Elnashar
• ETIOLOGY
 Family: Hepa DNA virus, whose DNA codes for four viral
products.
 Nucleic ac structure: Circular double-stranded DNA with
single-stranded portions
 Genome size: 3 - 4 Kb
 Envelop: yes
 Incubation period:
Long (up to 180 days).
Aboubakr Elnashar
2. DIAGNOSIS
 CLINICAL PICTURE
Most infections during pregnancy: chronic, asymptomatic
Acute infection:±asymptomatic and anicteric.
50%: asymptomatic.
Physical Exam
 Urticarial rash
 Arthralgias and arthritis
 Myalgias
 Hepatomegaly and/or right upper quadrant tenderness
 Jaundice is less common.
Aboubakr Elnashar
4/16/2022
2
 Outcome of acute HBV infection
Aboubakr Elnashar
HEPATITIS B LAB MARKERS
• Universal screening recommended: Maternal serologic testing
for HBsAg. If HbsAg positive, perform HBV DNA viral load
• HBsAg: Marker of current infection
HBeAg:
marker of active replication
at increased risk for transmitting HBV
HBV DNA: Viral load
Anti-HBs: resolved infection/immunity after immunization
Anti-Hbe: Identification of person with lower risk for
transmitting HBV
Aboubakr Elnashar
Aboubakr Elnashar Aboubakr Elnashar
3. TRANSMISSION
By any body fluid, but exposure to virus-laden serum is the most
efficient mode of transmission.
1. Maternal To Child Tansfer: Risk of vertical transmission: 30
% Related to maternal Viral Load
2. Sexual
3. Blood
Aboubakr Elnashar
1. MTCT
Aboubakr Elnashar
4/16/2022
3
• In utero (<10%) (Gambarin-Gelwan Clinics Liv Disease 2007)
• Transplacental viral infection is uncommon {viral DNA is rarely found in
amnionic fluid or cord blood} (Towers et al, 2001).
• Associated with
• Acute HBV in 3rd trimester
• Maternal HBeAg and high HBV DNA
• History of threatened preterm labor
• HBV in the placenta
• At the time of delivery: Most neonatal infection is vertically transmitted by
peripartum exposure
• After birth
• Breastfeeding not associated with transmission 2
• ±related to scarification, other parenteral exposures
Aboubakr Elnashar
Mother-to-child transmission of virus in women with chronic viral hepatitis. Potential opportunities for
transmission of viral infection from mother to infant can occur in utero, or during the peripartum and postpartum
periods.Data on in- utero transmission of hepatitis viruses are limited and based on detection of viraemia in
newborns within days of birth. As prenatal invasive procedures can theoretically lead to transfer of infectious blood
or body secretions from the maternal to the fetal compartment, this risk needs to be considered when
contemplating their use. Mother- to- child transmission (MTCT) requires the mother to be viraemic. Thus, the risk
period in mothers experiencing acute hepatitis (from any of the hepatitis viruses) will be shorter than in mothers
with chronic hepatitis (hepatitis B virus (HBV), hepatitis C virus (HCV) or hepatitis D virus infection). In women
with chronic HBV or chronic HCV infection, the most common period of transmission is during the peripartum
Aboubakr Elnashar
Risk of Perinatal Hep B Transmission
Positive for HBsAg only: <10% of infants infected
Measurement of viral DNA has replaced eAg as the most
sensitive test of viral activity.
HBV DNA < 108 copies/mL= 0% transmission
HBV DNA > 108 copies/mL= 32% transmission
Without
immunoprophylaxis
HBIG and HBV vaccine
series
HBeAg positive 70-90% 5-10%
HBeAg negative 10-40% <5%
Aboubakr Elnashar
2. Sexual
 Primary mode of transmission in US
 by direct contact with
Blood, semen, vaginal fluids, saliva
It is STD: fortunately there HBV vaccine
 Sex partners of HBsAg-positive persons (CDC, 2010)
counseled to use methods (e.g., condoms) to protect
themselves from sexual exposure to infectious body fluids,
unless they have been demonstrated to be
immune after vaccination (anti-HBs >10 mIU/mL) or
previously infected (anti-HBc positive).
Aboubakr Elnashar
4. HEPATITIS & PREGNANCY
IMPACT OF HBV ON PREGNANCY
Maternal risks
increased PTL, though studies are mixed.
Increased risk of gestational diabetes mellitus but no major
effect on other pregnancy outcomes.
Fetal risks: Related to PTL and gestational diabetes mellitus.
IMPACT OF PREGNANCY
Alanine aminotransferase (ALT) flares during pregnancy are
usually self- limiting, and reflect immunological and hormonal
changes.
Aboubakr Elnashar
Wedemeyer H, et al. Dtsch Med Wochenschr.2007;132:1775-1782.
EASL Clinical Practice Guidelines. J Hepatol.
Management
Liver disease
Treatment before and during pregnancy;
continue treatment after delivery
Advanced
Treatment before pregnancy; if response,
stop treatment before pregnancy
Moderate, no cirrhosis
Treatment in last trimester with “B”
category drug with post-partum
discontinuation
Mild, very high
viraemia
Pregnancy before treatment
Mild, low viraemia
5. MANAGEMENT
a. Periconceptional
Aboubakr Elnashar
4/16/2022
4
b. Antenatal
Maternal prevention:
HBV vaccination recommended for pregnant women who are
HBsAg and at high risk of HBV acquisition
Serologic testing for immunity (HBsAb) prior to vaccination is
not required but may be cost effective.
• Maternal TT: Tenofovir Disoproxil Fumarate (TDF)
• recommended for pregnant women with elevated HBV viral
load
• starting at 28 w.
Aboubakr Elnashar
 High-risk mothers who are seronegative CDC, 2010
Vaccine can be given during pregnancy.
Her husband infected with hepatitis B,
Household contacts of people infected with hepatitis B
Jobs that expose them to human blood or other body fluids
Travel to countries where hepatitis B is common
Ch liver or kidney disease,
kidney dialysis patients
Diabetes
HIV infection.
Aboubakr Elnashar
Aboubakr Elnashar
• Lamivudine
100 mg/day
From 28 t0 32 w
 in patients with HBV DNA > 108 copies/m
Decreased transmission from 28.0% to 12.5%
No adverse events (van Zonneveld M, et al. J Viral Hepat.
2003;10:294-297).
 Telbivudine (Tyzeka)
 600mg/d
 From 28-32 w
Aboubakr Elnashar
 Results of giving antiviral therapy in 3rd T of pregnancy
 Significant maternal HBV DNA reduction.
 No significant changes in ALT, creatinine, or creatine kinase
 No increased risk of maternal or f serious adverse events.
 Infants have significantly less HBsAg, HBeAg, and HBV
DNA positivity compared with controls.
 Rates of immune prophylaxis failure and MTCT are
significantly lower in infants
Aboubakr Elnashar
c. LABOUR
No role for caesarean delivery {No effect on HBV transmission}
Avoid amniocentesis
d. Postpartum
Breast feeding:
Provided the infant receives HBIG and HBV vaccination
Although virus is present in breast milk, the incidence of
transmission is not lowered by formula feeding
 Maternal Follow-up:
 ALT flares post-partum usually self-limiting; monitor for 3–6
months
 Assess the need for antiviral treatment
Aboubakr Elnashar
4/16/2022
5
 Neonatal post-exposure prophylaxis
 HBIG and HBV vaccine within 12 hs of birth for infants born
to women with HBSAg+ or unknown HBV status.
 Universal HBV vaccination within 24 hs of birth for medically
stable infants >2kg born to women with HBSAg- status.
 Birth dose vaccine is followed by completion of the 3-dose
infant vaccine series.
 Infant Follow- up: Serology 3 months after completing
vaccination course, usually at age 9 months
Aboubakr Elnashar
MTCT prevention
1. Timely neonatal HBIG and vaccine birth dose (as
soon as possible within 24 hours of birth), followed
by a standard course of vaccine.
2. Maternal antiviral prophylaxis with tenofovir
disoproxil fumarate starting at 28–30 w
3. No role for caesarean delivery amniocentesis.
4. Postpartum maternal antiviral prophylaxis might be
considered in situations where infant HBIG not
available.
Aboubakr Elnashar
Aboubakr Elnashar
Algorithm for women positive for HBV.
a | A multifaceted approach is needed to identify and prevent mother- to- child
transmission of hepatitis B virus (HBV). All pregnant women need to be tested for HBV.
For mothers positive for the HBV surface antigen (HBsAg), a risk assessment for
mother- to- child transmission, maternal treatment if indicated and postnatal vaccination
of all newborn infants are the elements that need to be implemented. An assessment of
maternal HBV DNA level in the first or second trimester and determination of the need
for antiviral prophylaxis is key.
b | Caesarean section should be reserved for obstetric indications only. Timely
administration of neonatal hepatitis B immune globulin (HBIG) and vaccine is critical
and, in settings where HBIG is not available, extended duration of maternal antiviral
therapy to protect infants until they respond to vaccination is a consideration.
ALT, alanine aminotransferase; HBeAg, HBVe antigen; TDF, tenofovir disoproxil
fumarate.
Aboubakr Elnashar
Take Home Message
• Perinatal is the most common mode of transmission
• Best prevention for transmission is active/passive
immunization
• Perinatal transmission occurs despite appropriate infant
passive-active immunization
• Antepartum antiviral therapy can prevent MTCT
• Neonates that are correctly immunized can be breast-fed
Aboubakr Elnashar

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hepatitis B.pdf

  • 1. 4/16/2022 1 Hepatitis B in Pregnancy Prof. Aboubakr elnashar Benha university Hospital, Egypt Aboubakr Elnashar CONTENTS 1. EPIDEMIOLOGY& ETIOLOGY 2. DIAGNOSIS 1. Clinical 2. outcome 3. lab markers 3. TRANSMISSION 4. HEPATITIS & PREGNANCY 1. impact on pregnancy 2. impact of pregnancy 5. MANAGEMENT 1. Pre conceptional 2. Antenatal: 1. hbv-infected women who desire pregnancy 2. How to minimize the risk of transmission ? 3. Labour: mode of delivery 4. Postpartum: 1. breast feeding 2. Maternal follow up 3. Infant follow up 5. ALGORITHM 6. TAKE HOME MESSAGE Aboubakr Elnashar 1. EPIDEMIOLOGY & ETIOLOGY Prevalence: 3.5% Africa: 6.1% Of the 400 million individuals with chronic HBV worldwide: 50% acquired their infections perinatally.  90% of infected infants will become ch carriers 2nd carcinogens after tobacco (WHO) In Egypt: The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Gish RG and AC Gadano. J Vir Hep. 2006. Aboubakr Elnashar Aboubakr Elnashar • ETIOLOGY  Family: Hepa DNA virus, whose DNA codes for four viral products.  Nucleic ac structure: Circular double-stranded DNA with single-stranded portions  Genome size: 3 - 4 Kb  Envelop: yes  Incubation period: Long (up to 180 days). Aboubakr Elnashar 2. DIAGNOSIS  CLINICAL PICTURE Most infections during pregnancy: chronic, asymptomatic Acute infection:±asymptomatic and anicteric. 50%: asymptomatic. Physical Exam  Urticarial rash  Arthralgias and arthritis  Myalgias  Hepatomegaly and/or right upper quadrant tenderness  Jaundice is less common. Aboubakr Elnashar
  • 2. 4/16/2022 2  Outcome of acute HBV infection Aboubakr Elnashar HEPATITIS B LAB MARKERS • Universal screening recommended: Maternal serologic testing for HBsAg. If HbsAg positive, perform HBV DNA viral load • HBsAg: Marker of current infection HBeAg: marker of active replication at increased risk for transmitting HBV HBV DNA: Viral load Anti-HBs: resolved infection/immunity after immunization Anti-Hbe: Identification of person with lower risk for transmitting HBV Aboubakr Elnashar Aboubakr Elnashar Aboubakr Elnashar 3. TRANSMISSION By any body fluid, but exposure to virus-laden serum is the most efficient mode of transmission. 1. Maternal To Child Tansfer: Risk of vertical transmission: 30 % Related to maternal Viral Load 2. Sexual 3. Blood Aboubakr Elnashar 1. MTCT Aboubakr Elnashar
  • 3. 4/16/2022 3 • In utero (<10%) (Gambarin-Gelwan Clinics Liv Disease 2007) • Transplacental viral infection is uncommon {viral DNA is rarely found in amnionic fluid or cord blood} (Towers et al, 2001). • Associated with • Acute HBV in 3rd trimester • Maternal HBeAg and high HBV DNA • History of threatened preterm labor • HBV in the placenta • At the time of delivery: Most neonatal infection is vertically transmitted by peripartum exposure • After birth • Breastfeeding not associated with transmission 2 • ±related to scarification, other parenteral exposures Aboubakr Elnashar Mother-to-child transmission of virus in women with chronic viral hepatitis. Potential opportunities for transmission of viral infection from mother to infant can occur in utero, or during the peripartum and postpartum periods.Data on in- utero transmission of hepatitis viruses are limited and based on detection of viraemia in newborns within days of birth. As prenatal invasive procedures can theoretically lead to transfer of infectious blood or body secretions from the maternal to the fetal compartment, this risk needs to be considered when contemplating their use. Mother- to- child transmission (MTCT) requires the mother to be viraemic. Thus, the risk period in mothers experiencing acute hepatitis (from any of the hepatitis viruses) will be shorter than in mothers with chronic hepatitis (hepatitis B virus (HBV), hepatitis C virus (HCV) or hepatitis D virus infection). In women with chronic HBV or chronic HCV infection, the most common period of transmission is during the peripartum Aboubakr Elnashar Risk of Perinatal Hep B Transmission Positive for HBsAg only: <10% of infants infected Measurement of viral DNA has replaced eAg as the most sensitive test of viral activity. HBV DNA < 108 copies/mL= 0% transmission HBV DNA > 108 copies/mL= 32% transmission Without immunoprophylaxis HBIG and HBV vaccine series HBeAg positive 70-90% 5-10% HBeAg negative 10-40% <5% Aboubakr Elnashar 2. Sexual  Primary mode of transmission in US  by direct contact with Blood, semen, vaginal fluids, saliva It is STD: fortunately there HBV vaccine  Sex partners of HBsAg-positive persons (CDC, 2010) counseled to use methods (e.g., condoms) to protect themselves from sexual exposure to infectious body fluids, unless they have been demonstrated to be immune after vaccination (anti-HBs >10 mIU/mL) or previously infected (anti-HBc positive). Aboubakr Elnashar 4. HEPATITIS & PREGNANCY IMPACT OF HBV ON PREGNANCY Maternal risks increased PTL, though studies are mixed. Increased risk of gestational diabetes mellitus but no major effect on other pregnancy outcomes. Fetal risks: Related to PTL and gestational diabetes mellitus. IMPACT OF PREGNANCY Alanine aminotransferase (ALT) flares during pregnancy are usually self- limiting, and reflect immunological and hormonal changes. Aboubakr Elnashar Wedemeyer H, et al. Dtsch Med Wochenschr.2007;132:1775-1782. EASL Clinical Practice Guidelines. J Hepatol. Management Liver disease Treatment before and during pregnancy; continue treatment after delivery Advanced Treatment before pregnancy; if response, stop treatment before pregnancy Moderate, no cirrhosis Treatment in last trimester with “B” category drug with post-partum discontinuation Mild, very high viraemia Pregnancy before treatment Mild, low viraemia 5. MANAGEMENT a. Periconceptional Aboubakr Elnashar
  • 4. 4/16/2022 4 b. Antenatal Maternal prevention: HBV vaccination recommended for pregnant women who are HBsAg and at high risk of HBV acquisition Serologic testing for immunity (HBsAb) prior to vaccination is not required but may be cost effective. • Maternal TT: Tenofovir Disoproxil Fumarate (TDF) • recommended for pregnant women with elevated HBV viral load • starting at 28 w. Aboubakr Elnashar  High-risk mothers who are seronegative CDC, 2010 Vaccine can be given during pregnancy. Her husband infected with hepatitis B, Household contacts of people infected with hepatitis B Jobs that expose them to human blood or other body fluids Travel to countries where hepatitis B is common Ch liver or kidney disease, kidney dialysis patients Diabetes HIV infection. Aboubakr Elnashar Aboubakr Elnashar • Lamivudine 100 mg/day From 28 t0 32 w  in patients with HBV DNA > 108 copies/m Decreased transmission from 28.0% to 12.5% No adverse events (van Zonneveld M, et al. J Viral Hepat. 2003;10:294-297).  Telbivudine (Tyzeka)  600mg/d  From 28-32 w Aboubakr Elnashar  Results of giving antiviral therapy in 3rd T of pregnancy  Significant maternal HBV DNA reduction.  No significant changes in ALT, creatinine, or creatine kinase  No increased risk of maternal or f serious adverse events.  Infants have significantly less HBsAg, HBeAg, and HBV DNA positivity compared with controls.  Rates of immune prophylaxis failure and MTCT are significantly lower in infants Aboubakr Elnashar c. LABOUR No role for caesarean delivery {No effect on HBV transmission} Avoid amniocentesis d. Postpartum Breast feeding: Provided the infant receives HBIG and HBV vaccination Although virus is present in breast milk, the incidence of transmission is not lowered by formula feeding  Maternal Follow-up:  ALT flares post-partum usually self-limiting; monitor for 3–6 months  Assess the need for antiviral treatment Aboubakr Elnashar
  • 5. 4/16/2022 5  Neonatal post-exposure prophylaxis  HBIG and HBV vaccine within 12 hs of birth for infants born to women with HBSAg+ or unknown HBV status.  Universal HBV vaccination within 24 hs of birth for medically stable infants >2kg born to women with HBSAg- status.  Birth dose vaccine is followed by completion of the 3-dose infant vaccine series.  Infant Follow- up: Serology 3 months after completing vaccination course, usually at age 9 months Aboubakr Elnashar MTCT prevention 1. Timely neonatal HBIG and vaccine birth dose (as soon as possible within 24 hours of birth), followed by a standard course of vaccine. 2. Maternal antiviral prophylaxis with tenofovir disoproxil fumarate starting at 28–30 w 3. No role for caesarean delivery amniocentesis. 4. Postpartum maternal antiviral prophylaxis might be considered in situations where infant HBIG not available. Aboubakr Elnashar Aboubakr Elnashar Algorithm for women positive for HBV. a | A multifaceted approach is needed to identify and prevent mother- to- child transmission of hepatitis B virus (HBV). All pregnant women need to be tested for HBV. For mothers positive for the HBV surface antigen (HBsAg), a risk assessment for mother- to- child transmission, maternal treatment if indicated and postnatal vaccination of all newborn infants are the elements that need to be implemented. An assessment of maternal HBV DNA level in the first or second trimester and determination of the need for antiviral prophylaxis is key. b | Caesarean section should be reserved for obstetric indications only. Timely administration of neonatal hepatitis B immune globulin (HBIG) and vaccine is critical and, in settings where HBIG is not available, extended duration of maternal antiviral therapy to protect infants until they respond to vaccination is a consideration. ALT, alanine aminotransferase; HBeAg, HBVe antigen; TDF, tenofovir disoproxil fumarate. Aboubakr Elnashar Take Home Message • Perinatal is the most common mode of transmission • Best prevention for transmission is active/passive immunization • Perinatal transmission occurs despite appropriate infant passive-active immunization • Antepartum antiviral therapy can prevent MTCT • Neonates that are correctly immunized can be breast-fed Aboubakr Elnashar