hepatitis b in pregnancy

Hepatitis B in Pregnancy Aboubakr elnashar

Benha university Hospital, Egypt

Aboubakr ElnasharAboubakr Elnashar

Contents Epidemiology

Natural history

Lab markers

Impact on pregnancy

Impact of pregnancy

Transmission How to minimize the risk of transmission ? Mode of delivery and Breastfeeding HBV-Infected Women Who Desire Pregnancy Algorithm

Take home message


Epidemiology

Of the 400 million individuals with chronic HBV

worldwide: 50% acquired their infections

perinatally.

90% of infected infants will become chronic

carriers of hepatitis B

2nd carcinogens after tobacco (WHO)

Gish RG and AC Gadano. J Vir Hep. 2006. Aboubakr ElnasharAboubakr Elnashar

Sequelae:

Chronic hepatitis

Cirrhosis

Carcinoma: Hepatocellular.

Mortality: 25% in perinatally acquired disease

7% in adult acquired disease

2 million/Y

9th leading cause worldwide

Liver International 2009; 29 : 135


Etiology Double-stranded DNA virus in the core particle. a hepa DNA virus whose DNA codes for four viral products. Incubation period Long (up to 180 days).


Clinical picture Most infections during pregnancy: chronic, Most infections during pregnancy: chronic, asymptomaticasymptomatic 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.


Clinical course After acute hepatitis

90%: recover completely.

10%: chronic hepatitis B: ¼ chronic liver disease

HBeAg positive: at greatest risk for hepatocellular

carcinoma (Yang and co-workers, 2002).


Hepatitis B Lab Markers

HBsAgHBsAg: : Marker of current infectionMarker of current infection

HBeAgHBeAg: : marker of active replication, marker of active replication,

Identification of persons at increasedIdentification of persons at increased

risk for transmitting HBVrisk for transmitting HBV

HBV DNA: HBV DNA: Viral load Viral load


Anti-HBs: marker of resolved infection

/immunity after immunization

AntiAnti--HbeHbe: : Identification of person with lower risk Identification of person with lower risk

for transmitting HBV for transmitting HBV


Impact of HBV on Pregnancy

Yes

Gestational diabetes

lower Apgar scores1,2

PPreterm delivery reterm delivery

No association with adverse pregnancy

outcomes3-5

1. Lao J Hepatol 2007 2. Tse J Hepatol 2005 3. Pastorek AJOG 1988 4. Wong Am J Perinatol 1999 5. To Aust N Z J Obstet Gynaecol 2003


Impact of Pregnancy Liver disease:Liver disease:

–– No worsening of liver disease in majority of No worsening of liver disease in majority of women women

(Terrault NA, et al, 2007)

---- Case reports of hepatic Case reports of hepatic exacerbations/fulminant hepatic failures exacerbations/fulminant hepatic failures

((MahtabMahtab MA, et MA, et al, al, 20082008))


Transmission By any body fluid, but exposure to virus-laden serum is the most

efficient mode of transmission.

1. Perinatal

Primary mode in E. Asia and SE Asia

2. Horizontal Transmission Infancy/Childhood

Primary mode in Africa

Close contact within households, medical procedures

3. Sexual

Primary mode of transmission in US

by saliva, vaginal secretions, and semen.

4. Parenteral

Second most common mode of transmission in US


Risk of Perinatal Hep B Transmission

Positive for HBsAg and HBeAg in the absence of

PEP: (MMWR 2005)

- 70%-90% of infants get infected

Positive for HBsAg only:

<10% of infants infected


Perinatal HBV Transmission Rates

Without

immunoprophylaxis HBIG and HBV

vaccine series

HBeAg positive 70-90% 5-10%

HBeAg negative 10-40% <5%


Role of maternal HBV DNA (Role of maternal HBV DNA (2828wks) on wks) on

transmisiontransmision

Measurement of viral DNA has replaced Measurement of viral DNA has replaced eAgeAg as the as the

most sensitive test of viral activity. most sensitive test of viral activity.

–– HBV DNA < HBV DNA < 10108 8 copies/mL= copies/mL= 00% transmission% transmission

–– HBV DNA > HBV DNA > 10108 8 copies/mL= copies/mL= 3232% transmission% transmission

World J Gastroenterol World J Gastroenterol 20042004; ; 1010: : 32153215––77..


In utero (<10%)1

–– TransplacentalTransplacental viral infection is uncommon viral infection is uncommon {viral DNA is rarely found in {viral DNA is rarely found in amnionicamnionic fluid fluid or cord blood} 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 delivery1

–– Most neonatal infection is vertically Most neonatal infection is vertically transmitted by transmitted by peripartumperipartum exposure exposure

After birth

– Breastfeeding not associated with transmission 2

– May be related to scarification, other parenteral exposures

1. Gambarin-Gelwan Clinics Liv Disease 2007 2. Beasley Lancet 1975


How to minimize the risk of

transmission ?

I. Antivirals to suppress HBV in mother

(reduce vertical transmission)

II. Post Exposure Prophylaxis (PEP) to

infant


Drug Pregnancy Category

IFN alfa-2b C

PegIFN alfa-2a C

Adefovir C

Entecavir C

Lamivudine (Epivir) C

Telbivudine (Tyzeka) B

Tenofovir (Viread) B

Drugs [package insert].

I. Antivirals


Lamivudine

100 100 mg/daymg/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

No complete prevention of transmission, even in

case of successful LAM treatment (van Zonneveld M, et al. J Viral Hepat. 2003;10:294-297).


10 RCTs

Shi Obstet Gynecol 2010;116:147–59 Aboubakr ElnasharAboubakr Elnashar

TelbivudineTelbivudine ((TyzekaTyzeka)) 600mg/d

From 28-32 w Han G, 2010


II. Prevention of HBV Transmission by =

Post Exposure Prophylaxis (PEP)Post Exposure Prophylaxis (PEP)

Active plus passive immunization:

most effective to prevent vertical transmission

protective efficacy of 95%

No Vaccine Passive

Immunization

Passive + Active

Immunization

Infants without HBV, % 5 72 95

1. Ranger-Rogez S, et al. Expert Rev Ant Infect Ther. 2004;2:133-145. 2. USPSTF, Screening for Hepatitis B infection. Recommendation statement 2004

.


Mode of delivery

has No effect on HBV transmission has No effect on HBV transmission (Yang J, et al. 2008)

Breast feeding

Although virus is present in breast milk, the Although virus is present in breast milk, the

incidence of transmission is not lowered by incidence of transmission is not lowered by

formula feeding: All Neonates who are correctly formula feeding: All Neonates who are correctly

immunized can be immunized can be breast-fed (Cornberg et al, 2008)


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

Chronic liver or kidney disease, kidney dialysis patients Diabetes

HIV infection.


Recommendations for HBV-Infected

Women Who Desire Pregnancy

Mild liver disease, low Mild liver disease, low viremiaviremia: : Pregnancy before Pregnancy before

treatment treatment

Moderate liver disease, no cirrhosis: Treatment Treatment

before pregnancy; if response, stop treatment before pregnancy; if response, stop treatment

before pregnancybefore pregnancy

Advanced liver disease: Treatment before and Treatment before and

during pregnancy; continue treatment after during pregnancy; continue treatment after

deliverydelivery

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


Algorithm for management of HBV

Pregnant woman

First trimester: HBsAg

HBsAg (-ve)

High risk: maternal HBV

vaccination

Infant receives

vaccine at birth

HBsAg (+) 28 wks

HBV DNA

< 108 copies/mL

Infant receives HBIg

+ vaccine at birth

HBV DNA

> 108 copies/mL

? treatment with

lamivudine at 32

wks

CLEVELAND J OF MEDICINE (76) MAY 2009 Aboubakr ElnasharAboubakr Elnashar

Take Home Message

Perinatal is the most common mode of transmission

Best prevention for transmission is active/passive

immunization

PerinatalPerinatal transmission occurs despite appropriate transmission occurs despite appropriate

infant passiveinfant passive--active immunizationactive immunization

AntepartumAntepartum antiviral therapy can prevent MTCT antiviral therapy can prevent MTCT

Neonates that are correctly immunized can be Neonates that are correctly immunized can be

breastbreast--fedfed


Sex partners of HBsAg-positive persons

CDC2010

should be counseled to use methods

(e.g., condoms) to protect themselves from sexual

exposure to infectious body fluids (e.g., semen and

vaginal secretions),

unless they have been demonstrated to be

immune after vaccination (anti-HBs >10 mIU/mL)

or

previously infected (anti-HBc positive).


Thank you Aboubakr elnashar


Management of HBsAg-Positive Persons CDC

To verify the presence of chronic HBV infection

1. HBsAg-positive persons should be retested.

2. Absence of IgM anti-HBc or the persistence of

HBsAg for 6 months indicates chronic HBV

infection.

Persons with chronic HBV infection should be

referred for evaluation to a physician experienced in

the management of CLD. 1. Some patients with chronic hepatitis B will

benefit from early intervention with antiviral treatment or

2. screening to detect HCC at an early stage.


Household, sexual, and needle-sharing contacts

of chronically infected persons should be identified.

Unvaccinated sex partners and household and

needle-sharing contacts should be tested for

susceptibility to HBV infection and should receive

the first dose of hepatitis B vaccine immediately

after collection of the blood sample for serologic

testing. Susceptible persons should complete the

vaccine series by using an age-appropriate vaccine

dose and schedule. Persons who are fully

vaccinated should complete the vaccine series.


To prevent or reduce the risk for transmission to

others

1. HBsAg-positive persons should be advised

concerning the risk for transmission to

household, sexual, and needle-sharing contacts

and the need for such contacts to receive

hepatitis B vaccination.

2. HBsAg-positive persons also should be advised

to use methods (e.g., condoms) to protect

nonimmune sex partners from acquiring HBV

infection from sexual activity until the partner

can be vaccinated and immunity documented;

3. cover cuts and skin lesions to prevent the

spread of infectious secretions or blood; Aboubakr ElnasharAboubakr Elnashar

4. refrain from donating blood, plasma, body

organs, other tissue, or semen; and refrain from

sharing household articles (e.g., toothbrushes,

razors, or personal injection equipment) that

could become contaminated with blood.


To protect the liver from further harm

1. HBsAg-positive persons should be advised to

avoid or limit alcohol consumption because of

the effects of alcohol on the liver;

2. refrain from starting any new medicines,

including OTC and herbal medicines, without

checking with their health-care provider; and

3. obtain vaccination against hepatitis A if liver

disease is determined to be present.


When seeking medical or dental care, HBsAg-

positive persons should be advised to inform those

responsible for their care of their HBsAg status so

that they can be appropriately evaluated and

managed.

HBV is not spread by hugging, coughing, food or

water, sharing eating utensils or drinking glasses, or

casual contact.

Persons should not be excluded from work, school,

play, child care, or other settings because they are

infected with HBV.


hepatitis b in pregnancy

Health & Medicine