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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 77 - Viral Hepatitis in Pregnancy

“Our relationship with the earth involves something more than pragmatic use, academic understanding, or aesthetic appreciation. A truly human intimacy with the earth and with the entire natural world is needed. Our children should be properly introduced to the world in which they live.” - Thomas Berry, from The Dream of the Earth


2018 Pizzella Malbec from La Posta Vineyards


PB#86 - Published October 2009 (Reaffirmed 2016)


Five Pearls

1. Those with chronic Hep B infection who are more likely to develop persistent hepatitis and cirrhosis will usually have persistent HBeAg indicating active viral DNA synthesis

2. Chronic HCV is associated with B-cell lymphomas and cryoglobulinemias; 20% lead to chronic active hepatitis and cirrhosis

3. Exposure to HBV should be managed through HBIG if patient's immune status is unknown.

4. Acute hepatitis presents as malaise, fatigue, nausea, RUQ pain/tenderness, anorexia, jaundice, or hepatomegaly. Chronic infection may lead to liver cirrhosis, portal hypertension, ascites, and, for HBV and maybe HCV, hepatocellular carcinoma

5. Successful vaccination against HBV can be determined by the presence of anti-HBs in the absence of anti-HBc and HBsAg; immunity conferred through natural infection can be determined by the presence of anti-HBc and anti-HBs in the absence of HBsAg


Hepatitis A (HAV)

- small RNA virus

- can produce asymptomatic or symptomatic infection after 28 days incubation

- replicate within liver and is excreted in bile

- fecal-oral transmission

- infected children are often asymptomatic, and 40% of adults with new HAV infection were found to have been in close contact with a child <6 years

- poor sanitation and hygiene can result in outbreaks

- foods must be heated to >185°F to inactivate virus; surfaces must be bleached

- serious complications from HAV infection are rare; 1% fatality rate (2% among adults >50 years old)

- does not lead to chronic disease, but can result in prolonged or relapsing infection in 10-15% of people for up to 6 months


Vaccine info for HAV

- vaccine is made from inactivated virus; introduced in 1996 in the U.S.

- pre-vaccine, hepatitis A (HAV) was the primary cause of acute hepatitis in the U.S.

- in the event of exposure to HAV in absence of vaccination, post-exposure immune globulin is available (but vaccination is preferred); vaccine should be provided in addition to HAV immune globulin

- indicated for patients with chronic liver disease, individuals who receive clotting factor concentrates, men who have sex with men, IV drug users, person who travel to high- or intermediate-endemic countries

- HAV vaccine comes in 2 doses, given 6-18 months apart, depending on the manufacturer

- in the combination vaccine (includes HBV), 3 doses are given at 0, 1, and 6 months

- 94-100% effective after 1st dose

- in highly endemic areas, pre-vaccine immunity screening is reasonable


Hepatitis B (HBV)

- small DNA virus

- whole virus particle is termed the "Dane" particle; it's important to know three distinct parts (antigens)

- hepatitis B surface antigen (HBsAg): present on the surface and circulates freely in the serum

- hepatitis B core antigen (HBcAg): present only in hepatocytes

- hepatitis B "e" antigen (HBeAg): encoded by same gene that codes for HBcAg; indicative of viral replication and an particularly infectious state

- transmitted parenterally (serum, blood) and sexual contact (serum, saliva, and semen)

- can be viable on surfaces for up to 7 days at room temperature even if blood no longer present

- blood donors are routinely screen for HBsAg (risk of transmission is 1-in-137,000 transfused units of blood

- 1% mortality

- 85-90% of infected individuals will see complete resolution of their symptoms and develop protective Ig; 10-15% become chronically infected

- in chronic infection, virus is still detectable in the blood, but patients are usually asymptomatic

- 15-30% of those with chronic infection will go on to develop chronic or persistent hepatitis and cirrhosis

- most common cause of chronic liver disease worldwide

- these are the individuals who will die of complications, such as hepatocellular carcinoma


Pearl: Those with chronic Hep B infection who are more likely to develop persistent hepatitis and cirrhosis will usually have persistent HBeAg indicating active viral DNA synthesis



Vaccine info for HBV

- indicated for health care workers, hemodialysis patients, IV drug users, patients in whom STD is diagnosed, patients with multiple sexual partners, staff in centers for the developmentally delayed, and international travelers to regions with high or intermediate prevalence

- not cost effective to screen for antibodies prior to vaccination

- vaccine is manufactured using recombinant DNA in yeast cultures

- 95% seroconversion

- vaccine can be combined with HAV vaccine (see HAV vaccine section above)

- a rapid schedule (days 0, 7, and 21-30 then booster at 12 months) is available if protection is needed imminently for travel or work

- should be administered to the deltoid (lower seroconversion rates if injected intragluteal or intradermal

- not contraindicated in pregnancy (in fact, it's recommended if they aren't found to be immune)

- if a person is exposed to the virus and lack known immunity, HBIG (antibody) should be administered within 24 hrs, and they should begin the vaccine series


Hepatitis C

- at least 6 distinct genotypes have been identified

- predominantly spread through IV drug abuse and blood transfusion (screening also warranted if they have tattoos, recipient of blood products before 1987 or from a donor who later tested positive for HCV, recipients of organ donation before 1992, person on hemodialysis, or patients with HIV)

- transmission occurs with 1-in-1,000,000 transfused units of blood

- as blood products are more thoroughly screened, the number of new cases resulting from IV drug use has increased proportionally

- acute infection occurs after 30-60 day incubation period

- 75% of patients will be asymptomatic

- at least 50% of infections become chronic

- chronic infection is associated with B-cell lymphomas and cryoglobulinemias

- most common cause for chronic liver disease in the U.S.

- not clearly linked to hepatocellular carcinoma

- concomitant infection with HIV accelerates progression and severity of hepatic injury


Hepatitis D

- incomplete viral particle that only causes disease in the presence of HBV

- when this magic happen, the HDV gets enveloped in HBsAg

- 20-25% of HBV carriers are also infected with HDV

- transmitted through blood

- chronic HDV is more severe than other forms of chronic viral hepatitis

- 70-80% of patients will go on to develop cirrhosis and portal HTN (15% of which will develop cirrhosis within 2 years of infection)

- 25% mortality


Hepatitis E

- higher incidence with poor sanitation and poor hygiene settings

- primarily waterborne (fecal-oral); also potentially through infected, undercooked shellfish

- in general, this is a self-limited infection with incubation period of 3-8 weeks (mean ~40 days)

- in pregnancy women, however, there's a risk of fulminant infection with 20% mortality rate if infection occurs in the 3rd trimester

- mortality rate may be as high as 100% in pregnant patients with HIV


How does acute hepatitis present?

- malaise, fatigue, nausea, RUQ pain/tenderness, anorexia, jaundice, or hepatomegaly

- patient may be anicteric but jaundiced elsewhere

- urine may be dark

- stools may be gray (fancy word: acholic)

- elevated alanine and aspartate aminotransferase (AST, ALT)

- often hyperbilirubinemia and/or hyperammonemia

- HDV is unique: initially, it's indistinguishable from HBV, but 2-4 weeks after apparent resolution of symptoms, patient will typically relapse and have a milder form and 2nd spike in transaminases (by then serologies for HDV will likely be positive)

Spider angioma

How does cirrhosis present?

- jaundice, muscle wasting, ascites, spider angiomata, palmar erythema, and, ultimately, hepatic encephalopathy


Management of acute hepatitis

- conservative management may be sufficient (rest, hydration, symptom management) unless the patient is encephalopathic, coagulopathic, or severely debilitated, in any of which hospitalization is warranted

- correct nutritional deficiencies, fluid and electrolyte abnormalities, correction of coagulopathy through FFP or cryoprecipitate (may also need RBCs or platelets)


Which tests do I order?

- if viral hepatitis is suspected, the specific virus can be identified through serum testing

- order these labs: Ig anti-HAV, Ig anti-HBc, Ig anti-HBs, IgM anti-HCV, along with liver panel (bili, ALT, AST, alk phos, albumin, and total protein)


WARNING: THIS IS THE MOST CONFUSING ASPECT IN THE WORLD OF HEPATITIS


Hepatitis A

- presence of IgM anti-HAV indicates acute HAV hepatitis

- presence of IgG anti-HAV indicates prior infection or vaccination

- remember: no chronic carrier state








Hepatitis B

- HBsAg predates clinical symptoms by 4 weeks on average and persists in the blood for 1-6 weeks

- the chronic carrier state is characterized by the persistence of HBsAg beyond the acute phase (>20 weeks) along with the absence of IgG anti-HBs, which, if detected, would indicate immunity status (the issue is that this IgG appears not until much later)

- there is a window in which HBsAg is undetectable nor is IgG anti-HBs present in high enough quantities; acute infection can still be diagnosed by IgG anti-HBc, which will appear 4-5 weeks after initial infection

Typical serological course after HBV infection

Typical serological course for progression to chronic HBV carrier state

- anti-HBc is also only present in the context of a natural infection (not immunization)

- vaccinated: presence of anti-HBs in the absence of anti-HBc and HBsAg

- infection-based immunity: presence of anti-HBc and anti-HBs in the absence of HBsAg



Great scott! (source: CDC)

Hepatitis C

- anti-HCV detected by ELISA

- antibody may not be present until 6-10 weeks after clinical symptoms appear

- hepatitis C viral RNA can be detected by PCR soon after infection (and in chronic disease)

- PCR is required to confirm infection because of the small but real false positive rates associated with serum antibody screening


Recall: false positive rates and positive predictive value are less accurate in lower prevalence populations (more stats fun!)


- DNA and RNA based testing can clarify the specifics of infection but should be interpreted by specialists

- Table 3 in the PB elaborates further on HCV testing (not included here)

- liver and other end-organ damage can continue despite the presence of antibody


Hepatitis D

- testing for hepatitis D antigen is available for serum and liver biopsy as well as IgM anti-HDV

- HDV antigen usually persists even in the presence of IgG anti-HDV

- like HCV and HIV, viremia and end-organ damage can continue despite presence of antibody


Hepatitis E

- antibody detection


Screening for viral hepatitis in pregnancy

- refer to liver disease specialist if a patient is a known or found to be a chronic carrier

- vertical transmission of HBV is primary etiology for chronically infected individuals worldwide

- risk-factor-based screening only detects 60% of carriers, so HBsAg should be screened for in all pregnant women

- if we know it's there, we can work to prevent vertical transmission to the newborn (at least for HBV)


Recall: vertical transmission is the passage of infectious agent from mother to baby during pregnancy or after birth by means of placental transmission, breastmilk, or direct contact with mom


Vertical transmission


Hepatitis B

- if HBsAg is present alone, risk of transmission is 10% without immunoprophylaxis

- if both HBsAg and HBeAg are present, risk of transmission is 90% without immunoprophylaxis

- risk of this transmission becoming a chronic carrier state is 10-15% for adults; if transmitted to a newborn, risk is 85-90% w/ 25-30% lifetime risk of serious or fatal liver disease

- risk of vertical transmission is lower if mom is exposed in the first trimester (up to 10%) versus the third trimester (80-90%)

- for seronegative mothers: the CDC recommends universal HBV vaccination of all infants no later than 2 months after birth (for preterm babies weighing <2000 g, the vaccine should be delayed for 1 month)

- for seropositive mothers or unknown status: the CDC recommends HBIG and HBV vaccine for the infant within 12 hours of birth, both given simultaneously in different appendages (then two more vaccinations within 6 months of life)

- this immunoprophylaxis is obviously not useful if an infant has already been infected in-utero

- risk factors for in-utero infection: seropositivity for HBeAg in mom, higher HBsAg titers and HBV DNA on PCR ("viral load"), and presence of HBV DNA in venous capillary endothelial cells

- unclear if operative vaginal delivery or internal fetal monitoring poses higher risk of transmission


Hepatitis C

- 2-8% risk of vertical transmission

- detectable viral RNA in the blood is requisite

- risk of transmission is >40% is patient is co-infected with HIV

- one cohort study also suggests an increased risk with higher viral loads, prolonged ROM (>6 hours) prior to birth and with the use of internal fetal monitoring intrapartum

- we have no immunoprophylactic measures to reduce risk of transmission

- patients with risk factors should be screened for antibodies


Hepatitis D

- rarely transmitted vertically

- same measures to prevent HBV transmission will work for HDV


Is c-section safer for the mom and baby in viral hepatitis?

- hell no. reserved for normal obstetric indications


What is the risk to the fetus with invasive prenatal diagnostic testing?

- limited data to guide counseling in patients who are chronic carriers

- goes without saying to hold off in the vent of acute viral hepatitis


Is breastfeeding contraindicated?

- acute HAV (remember no chronic carrier state): not contraindicated, just practice good hygiene

- HBV: not contraindicated if HBsAg seropositive at time of birth nor after birth if newborn receives immunoprophylaxis (both HBIG and HBV vaccine)

- HCV: not contraindicated

- HDV: not even mentioned (but according to the CDC not contraindicated)

- HEV: no data to guide counseling; anti-HEV antibody and HEV RNA are detectable in breastmilk but at significantly lower amounts than mother's serum


A few words on immunotherapy and antiviral agents


Hepatitis A

- no treatment available

- post-exposure immunoprophylaxis is warranted for individuals who haven't been immunized

- safe to administer hepatitis A immune globulin in pregnancy for this purpose

- administered IM as 0.02 mL/kg, this confers protection of 80-90% for up to 3 months

- not useful if you wait longer than 2 weeks after exposure

- patients should receive vaccine, too


Hepatitis B

- no great treatment available, also lamivudine has promise for reducing in-utero transmission risk

- similar results from use of HBIG late in pregnancy


Hepatitis C

- no treatments available, though interferons are being explored as possible future therapies for pregnancy


What is the risk of exposure to me as a healthcare worker?

- most likely going to happen by needle stick injury

- 20-30% risk of HBV transmission; "splash" exposure to mucosa is also possible

- risk of HCV transmission is less than HBV but higher than HIV (0.3%)

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