Viral Hepatitis in Pregnancy, with Dr. Brenna Hughes

We were lucky enough to get a sneak peak at ACOG’s newest Clinical Practice Guideline #6 on Viral Hepatitis in Pregnancy. We sat down with co-author Dr. Brenna Hughes, professor of obstetrics and gynecology and Vice Chair of Obstetrics and Quality at Duke University, to get highlights of the newest updates and changes concerning hepatitis in pregnancy.

Background

  • There are five types of viral hepatitis: A, B, C, D, E

    • A and B are preventable through vaccination

    • B and C are recommended for screening in pregnancy.

  • Screening and vaccination is important, as these infections cause morbidity for pregnant folks.

  • Hepatitis A — small case-fatality and rare complications

    • Associated with food-borne outbreaks

    • Fecal-oral contamination or foodborne outbreaks related to contaminated food/water

  • Hepatitis B — highly pathogenic and infectious

    • Perinatal transmission is single largest cause of chronic infection worldwide.

    • Also associated with sexual contact, IV drug use, contaminated blood product.

    • Mortality 1%

      • 85-90% of adults will experience resolution of physical findings and develop antibody.

      • 10-15% will develop chronic infection, with a minority of those continuing with viral replication and active viral DNA synthesis.

  • Hepatitis C

    • Most commonly reported bloodborne infection in the US

      • Principal risk factor: IV drug use

    • 75% of individuals are asymptomatic with infection

    • Can be concomitantly spread with HIV

  • Hepatitis D

    • Incomplete viral particle that exists only in presence of hepatitis B

    • Transmission primarily blood borne

    • Produces more severe disease than other forms of chronic hepatitis

      • 70-80% develop cirrhosis and portal hypertension, 15% within 2 years of initial onset of acute illness

        • This is compared to just 15-30% of patients with Hep B alone who develop cirrhosis and portal hypertension over time.

  • Hepatitis E

    • Similarly to hepatitis A, associated with fecal-oral transmission

    • Generally self-limited viral illness

      • In pregnant persons, higher risk of fulminant hepatitis E with 20-35% fetal mortality and significant maternal morbidity (including need for transplant).

      • Rare in US

New Updates in Screening for Hepatitis B

  • ACOG recommends triple panel screening for all pregnant patients without documented negative triple screen after age 18, or haven't completed HepB vaccine series, or who have ongoing risk for HepB infection regardless of prior vaccination / testing.

    • This encompasses obtaining a:

      • HepB surface antigen (Hep B sAg)

      • HepB anti-surface antibody (anti-HBs)

      • HepB total core antibody (total anti-HBc)

    • A triple panel provides opportunity to inform decisions regarding treatment (if needed) or vaccination.

    • If positive surface antigen — additional testing will help determine type of infection and chronicity.

  • ACOG still recommends early universal prenatal screening for HepB sAg in all pregnancies regardless of testing and vaccination status.

    • 12-18% of patients still don’t receive even this baseline level of screening.

ACOG CPG 6

Managing Hepatitis B in Pregnancy

  • Pregnancy is well tolerated in those with hepatitis B infection without advanced liver disease.

    • There is a risk of hepatitis flare, particularly postpartum.

  • Those with chronic hepB and a viral load of > 200,000 IU/mL should be on antiviral therapy in the third trimester to reduce risk of perinatal transmission.

    • Some patients with lower VL may also be on antivirals if indicated for their own risk/health.

  • Vertical transmission is low with amniocentesis and shared-decision making can be employed when making decisions on this.

  • There is insufficient evidence to suggest invasive obstetric procedures (FSE, episiotomy, operative delivery) increase transmission risk, but there are some reports of increased risk with neonate coming to contact with infected blood.

  • All neonates of individuals with HBsAg-positive status or unknown status should receive HBIG and hepatitis B vaccine within 12 hours of birth.

  • Breastfeeding can proceed unless there are other contraindications.

    • Tenofovir can be continued during breastfeeding.

Hepatitis C: Screening, Treatment, and Pregnancy Pearls

  • ACOG recommends pre-pregnancy screening for hepatitis C virus infection and treatment.

    • Ideally, pregnant folks will get screened for hepatitis C antibody at the first prenatal visit of each pregnancy.

      • If positive —> assess hepatitis C viral PCR testing to confirm active infection vs cleared infection or false positive.

    • There are no treatment options for hepatitis C diagnosed in pregnancy — but there are really successful treatment options outside of pregnancy.

      • OB/GYNs can help get these patients to successful treatment in the postpartum period with prenatal screening.

    • Ribavirin achieves virology cure in large proportion of patients.

      • If patients are taking prior to pregnancy, couples should wait 6 months after completion of therapy due to possible teratogenic effects.

  • In pregnancy, there are no known preventive measures to reduce risk of vertical transmission.

    • Risk is generally low for amniocentesis and CVS: use shared decision making in decision to proceed.

    • There is insufficient evidence to suggest routine invasive obstetric procedures should be avoided (internal monitoring, episiotomy, operative delivery) but can be considered/minimized when possible.

      • No evidence pre labor cesarean decreases transmission risk.

    • Breastfeeding is not discouraged in patients with active hepatitis C.

      • Not enough data on cracked/bleeding nipples.

Immunization in Pregnancy

  • Both hepatitis A and hepatitis B vaccination are safe in pregnancy!

    • Newer hepatitis B vaccines do not have sufficient data (HepBZ-CpG and Hepb Vaccine Recombinant) — so need to know your manufacturer.

    • There is a combination vaccination for adults that can be used in pregnancy as well!

Viral Hepatitis in Pregnancy

UPDATE TO THE PODCAST:

SMFM and ACOG have recently updated their guidance to recommend universal hepatitis C screening in pregnancy! Check out the Practice Advisory here.

What is hepatitis anyway?

  • Hepatitis typically refers to a viral infection of the liver.

  • One of the most common and potentially serious infections that can occur in pregnant women!

  • Typically defined by vague symptoms (malaise, fatigue, anorexia, RUQ or epigastric pain)

    • Physical findings can (but do not always) include jaundice, upper abdominal tenderness, hepatomegaly

    • Other findings: dark urine, gray/white stool; if severe, coagulopathy or encephalopathy

  •  Five different types of hepatitis that can affect pregnancy: A, B, C, D, E

Hepatitis Basics by Virus

Hepatitis A

a.    Small RNA virus 

b.    Transmission: fecal-oral contamination, most commonly by children who are asymptomatic

                                               i.     Ex. Poor hand hygiene or food handling

c.     Complications: serious complications rare (1%)

d.    Chronic infection: no, although 10-15% of symptomatic individuals can have symptoms lasting up to 6 months

Hepatitis B/D

a.    Small DNA virus

b.    Transmission: parenteral and sexual contact

                                               i.     At risk – IVDU, high risk sexual behavior

c.     Complications:

                                               i.     Mortality 1%

d.    Chronic infection: 

                                               i.     10-15% will be chronically infected but asymptomatic, no lab abnormalities

                                             ii.     Small subset (15-20%) of those chronically infected will be at risk of developing chronic liver disease (hepatitis, cirrhosis, hepatocellular carcinoma)

e.    Hepatitis D – can only occur with or after Hep B infection (‘co-infection’); produces severe disease more rapidly than Hep B alone

                                               i.     70-80% will develop cirrhosis and portal hypertension, 15% of which will occur with 2 years

                                             ii.     Mortality approaches 25%

Hepatitis C

a.    Transmission: parenteral (blood transfusions – 1 in 1,000,000; IVDU), NOT sexual contact

b.    Complications: 75% infections asymptomatic

c.     Chronic infection: might higher than Hep B, at least 50% infected individuals progress to chronic infection 

                                               i.     20% of chronically infected developed hepatitis or cirrhosis

                                             ii.     Increased risk of B-cell lymphomas and cryoglobulinemia

Hepatitis E

a.    Rare in US, more common in developing countries

b.    Like Hepatitis A, usually due to poor sanitation such as fecal contamination of drinking water

c.     Typically self-limited; however notably high maternal mortality rate (20%) in pregnant women in third trimester. 

Testing for Hepatitis Virus

Hep A

a.    Acute infection – IgM antibodies

b.    No chronic infection, but past infection or vaccination will show +IgG antibodies

Hep B

a.    Three principal antigens:

                                               i.     Hep B surface antigen (HBsAg) present on surface of virus and circulates freely in the serum 

                                             ii.     Hep B core antigen (HBcAg) present only in liver cells, does not circulate in serum

                                            iii.     Hep B e antigen (HBeAg) indicates extremely high viral load and active viral replication 

                                            iv.     Serologic course:

1.    In general, positive HBsAg in pregnancy should prompt further workup for either acute infection or chronic carrier state

Hep C

                                               i.     Diagnosed by detection of Hep C antibody (may not present until 6- 10 weeks after onset of clinical illness)

                                             ii.     Can also detect HCV viral RNA load

Prevention and treatment of maternal infection

Hepatitis A

a.    Vaccination!

                                               i.     Recommended for adults at increased risk of infection or complications from liver disease – i.e. patients with chronic liver disease, men who have sex with men, drug use, traveling to endemic areas

b.    Post-exposure treatment: both HAV vaccine + immune globulin 

Hepatitis B

a.    Vaccination!

                                               i.     Recommended for healthcare workers, hemodialysis patients, drug users, persons with multiple sexual partners (>1 during past 3 months??) or STD diagnosis, traveling to endemic areas

                                             ii.     Can receive either separate HAV/HBV vaccine or together in combination vaccine

                                            iii.     Not contraindicated in pregnant women – actually recommended if at risk for infection!

b.    Post-exposure treatment: both HBV vaccine + immune globulin (same as Hep A)

                                               i.     Within 24 hours of exposure but not more than 14 days after exposure

General treatment of hepatitis in pregnant women:

a.    Acute -  Can generally be managed as outpatient with supportive management unless:

1.    Encephalopathy

2.    Coagulopathy – administer blood or clotting factors as needed

3.    Severe debilitation 

                                             ii.     All patients should avoid upper abdominal trauma, avoid contact with household members and sexual partners until treated/received appropriate prophylaxis

b.    Chronic – referred for evaluation to a liver specialist

 

Perinatal Transmission 

Hep B

a.    Perinatal transmission is the single largest cause of chronically infected individuals worldwide!!!

                                               i.     ACOG recommends routine prenatal screening of all pregnant women

What if mom has Hep B?

                                               i.     Without prophylaxis, 10-20% of seropositive women will transmit the virus to the fetus

1.    These babies will have 85-95% risk of chronic infection (vs. 5-10% risk if acquired as an adult)

                                             ii.     If acute infection occurs in pregnancy -> Higher rate of transmission later in gestation (10% if maternal infection occurs in first tri, 80-90% if maternal infection occurs in third tri)

iii. Avoid FSE/early amniotomy in labor to reduce risk of transmission.

What if mom’s Hep B status is unknown?

                                               i.     If mom is seropositive or if status unknown -> baby should receive HBIG and Hep B vaccine within 12 hours of birth (active immunization)

                                             ii.     However, this treatment will not prevent HBV infection if baby already infected in utero

 Hep C

a.    Unlike Hep B, universal prenatal screening not recommended; should only be screened for Hep C ab if at increased risk

b.    Vertical transmission rate 2-8% with moms who have detectable levels of HCV RNA in blood (rare if viral load undetectable)

c.     No known preventive measures to lower risk of vertical HCV infection of neonates

d.    Should not alter mode of delivery

 

How should women with viral hepatitis be treated during pregnancy and postpartum?

a.    No specific therapy is available for treatment of acute infection 

b.    Hep B: antiviral medication (lamivudine) can treat chronic infection and suppress viral replication decreasing the risk of in utero HBV infection 

c.     Hep C: no current antiviral treatment recommended in pregnancy

d.    Breastfeeding not contraindicated with the following:

                                               i.     HAV with proper hygiene

                                             ii.     HBV if infant received HBIG and HBV vaccine

                                            iii.     HCV