Hepatitis B……. Chronic…… Pregnant A review of review articles Bridget A. Buyea

Definition a disease of type A, B, C, D, or E. you can get hepatitis if someone pees in your soup or you don’t use a condom, actually, you can get hepatitis from spit, so don’t kiss anybody without using a dental dam or else you WILL die (1) Chronic hepatitis represents a series of liver disorders of varying causes and severity in which hepatic inflammation and necrosis continue for at least 6 months (2) 1.Hepatitis. 2.Dienstag, J. Chronic Hepatitis. Harrison’s Prinicples of Internal Medicine. pp t edition. Copyright 2008

Blast from the past: Step 1 HBsAg: Antigen found on surface of HBV HBsAb: Antibody to HBsAg, provides immunity to hepatitis B HBcAg: Antigen associated with core of HBV HBcAb: Antibody to HBcAg; IgM HbcAb is an indicator of recent disease; IgG HbcAb signifies chronic disease HBeAg: a second, different antigenic determinant in the HBV core. Important indicator of active viral replication and therefore transmissibility. High HBEAg level = high Enfectivity HBeAb: antibody to e antigen; indicates low transmissibility Above info from: Hepatitis Serologic Markers. Pg 173. First Aid for Step 1

Diagnosis?

So why do we care? “infection at birth is associated with clinically silent acute infection but a 90% chance of chronic infection while infection in young adulthood in an immunocompeta]ent person is typically associated with clinically apparent acute hepatitis but a risk of chronicity of only approximately 1%” (2) Remember, this is a disease people can die from. They have a shortened life expectancy depending on their viral load and HBeAg + or – “Approximately 600,000 people DIE each year secondary to acute or chronic consequences of HBV” (3) 3 Giles et al. Chronic Hepatitis B Infection and Pregnancy. CME Review Article. Obstetrical And Gynecological Survey. Volume 67. Number 1. Copyright 2012 Lippincott Williams and Wilkin

Chronic Hepatitis B + Pregnancy = No issues with fertility or conception No difference in preterm delivery, birth weight, neonatal jaundice, congenital anomalies, perinatal mortality unless… +cirrhosis: increased risk of SAB; gHTN, abruption, pp hemorrhage (versus general population)

MODES OF TRANSMISSION VERTICAL In Utero At Delivery HORIZONTAL Childhood

AT DELIVERY MOST FREQUENT ROUTE OF TRANSMISSION (we think) Based on diagnosis of +HBsAg at/after 1 month of life All babies should get 2 interventions at birth if mom is Hep B +…………… (I hope someone answered) “This strategy has been shown to reduce transmission by up to 90%”!!

IN UTERO 1. How is Hep B transmitted in general? 1. Ex. We know Hep A is transmitted fecal-oral 2. HOW is it transmitted in utero? 3. WHEN is it transmitted in utero? 1. Someone better have answered this one. 2. Not sure: transplacental? Maternal blood leak? 3. Not sure: but know that it can and DOES happen… and traditional regimen of treating AT delivery does not prevent this transmission

So what do we do? We want to prevent transmission regardless of route!

Not these things: Some +/- ideas that don’t have the evidence to back them up to make the experts recommend them HBIG administration q4w starting at 24 wga Some studies reported statistically significant findings to support this regimen, unfortunately there were significant methodological flaws in the studies  Cesarean delivery has shown a protective effect in preventing HVB transmission …depending on which study you look at :\

New, Exciting, Alternatives!! With the discovery that treating HIV in pregnant women can significantly reduce vertical transmission rates, that thought seems to have been carried over to the Hepatitis B world…and they are using some of the same drugs that were studied in HIV + moms

When antepartum treatment REALLY matters

ALSO:

….But we still need “a properly designed, prospective, randomized, controlled trial to address the efficacy of antiviral therapy in the interruption of vertical transmission”….

NEVERTHELESS! There are encouraging new studies showingthe efficacy of antepartum treatment withantivirals to decrease the rate of verticaltransmission It has been shown the tradition WHO regimenof HBIG + Hep B vaccine AT birth is LEASTeffective with women who have a high viralload (>6/8/10 log10) and women with+HBeAg….. So, why don’t we DECREASE the viral loadantepartum or attempt to seroconvert theirHBeAg status?

STUDY SUPPORT LAMIVUDINE Studies with n= 3, 8, 12 showed decreased rates of transmission (also study of n=114 but issues with intent- to-treat statistics) TELBIVUDINE Prospective, nonrandomized, open label study Treatment arm 30% achieved undetectable viral load vs 0% in no-treatment arm At delivery: 6.32% vs % At 28weeks old: 2.11% vs 13.04%

TENOFOVIR!!!!!! o CLASS B o No Hepatitis B pregnancy studies BUT has been used in HIV + pregnancies and evidence from studies related to that illustrate no adverse effects during pregnancy (large power)

Okay, so what about BREASTFEEDING?? No Antivirals + immunoprophylaxis Do it! Antivirals +immunoprophylaxis Don’t  unless d/c antivirals 1 month post partum to “limit exposure of the infant to these drugs through breastmilk…need to monitor serial ALT and HBV DNA” in mom to detect Hepatitis flares that could occur 2/2 d/cing treatment..

Questions we are left with Should ALL Chronic Hepatitis B moms be treated with antivirals? If so, when should it start? How often do we monitor ALT/HBV DNA/HBeAg for people who are treated and for people who aren’t? Do the benefits of breastfeeding outweigh the risks to the moms of d/cing treatment? (Especially in the HBeAg+ moms who should be on treatment for 48 months!)