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Management of hepatitis B in pregnancy: Weighing the options

May 1, 2009|Cleveland Clinic Journal of Medicine
Tram T. Tran, MD
Author and Disclosure Information

Tram T. Tran, MD
Associate Professor of Medicine, Geffen UCLA School of Medicine; Medical Director, Liver Transplantation, Center for Liver Disease and Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA

Correspondence: Tram T. Tran, MD, Medical Director, Liver Transplantation, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 590, Los Angeles, CA 90048; tram.tran@cshs.org

Dr. Tran reported that she has no financial interests or relationships that pose a potential conflict of interest with this article.

This article was developed from an audio transcript of Dr. Tran’s lecture at the “Seventh Annual Liver Update 2008,” a CME course. The transcript was formatted and edited by the Cleveland Clinic Journal of Medicine staff for clarity and conciseness, and was then reviewed, revised, and approved by Dr. Tran. The discussion at the end of the article was developed in the same way, and then reviewed, revised, and approved by the discussion participants. Disclosure and affiliation information for the discussion participants is included in “Continuing Medical Education Information,” at the beginning of this supplement.

Dr. Tran and the discussion participants received honoraria for contributing to this supplement and the CME course on which it was based. The honoraria were paid by the Cleveland Clinic Center for Continuing Education from educational grants provided by Bristol-Myers Squibb Company and Gilead Sciences, Inc., that supported the course and this supplement. These grantors had no input on the content of the course or this supplement.

ABSTRACT

Maternal screening and active and passive immuno­prophylaxis have reduced the perinatal, or vertical, transmission of hepatitis B virus (HBV) dramatically. Without immunoprophylaxis, chronic HBV infection occurs in up to 90% of children by age 6 months if the mother is positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Even with immunoprophylaxis, perinatal transmission is possible when the mother is highly viremic and HBeAg positive. Antiviral therapy during the third trimester of pregnancy in high-risk women with chronic HBV infection reduces viral load in the mother and may decrease the risk of perinatal transmission, although data are lacking. Safety data in pregnancy are most robust with lamivudine and tenofovir compared with other therapies. Careful discussion with the patient regarding the risks and benefits of therapy is warranted. Prophylaxis remains the best method of prevention of perinatal transmission.

KEY POINTS

  • Hepatitis B immune globulin at the time of birth plus three doses of the recombinant hepatitis B vaccine over the first 6 months of life is up to 95% effective in
    preventing perinatal transmission.
  • Despite successful screening and vaccination, perinatal transmission of HBV is still possible if maternal viral load is high.
  • Antiviral treatment during the third trimester of pregnancy may reduce perinatal transmission of HBV; the benefit appears most pronounced with high maternal viremia.

MANAGEMENT STRATEGY

Adapted from Current Hepatitis Reports (Tran TT, et al. Management of the pregnant hepatitis B patient. Current Hepatitis Reports 2008; 7:12–17). © 2008 with kind permission from Current Medicine Group LLC .
Figure 1. Management of hepatitis B virus (HBV) infection during pregnancy starts in the first trimester with assessment of hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to HBsAg (anti-HBs). Treatment decisions are based on viral load (HBV DNA) levels at week 28 and presence or absence of a history of perinatal transmission. HBIg = hepatitis B immunoglobulin
Decisions regarding treatment of HBV infection during pregnancy are based on the assessment of HBsAg, antibody to HBcAg, and antibody to HBsAg in the first trimester (Figure 1).18 If the mother is HBsAg negative, then the maternal HBV vaccination series is initiated and the infant is vaccinated at birth.

If the mother is HBsAg positive in the first trimester, history of perinatal transmission and an assessment of viral load at week 28 guide further management decisions. All children of HBsAg-positive mothers receive HBIg in addition to vaccination at birth.

Women with high viral loads can be considered for treatment with antiviral therapy, but a comprehensive discussion of risks and benefits needs to take place before opting for treatment as the data are too limited at this time to advocate therapy. One strategy for therapy is the use of lamivudine, tenofovir, or telbivudine starting at 32 weeks of pregnancy; the HBV DNA level that warrants treatment depends on the presence or absence of a history of perinatal transmission. If a previous child was HBV positive, concerns about the risk of perinatal transmission may be higher, so the threshold for treatment may be lower (HBV DNA > 106 copies/mL) than if the previous child were not positive for HBV. If the previous child was not HBV positive, treatment might be considered with HBV DNA levels greater than 108 copies/mL.

SUMMARY

Although a case can be made for treatment of HBV infection during pregnancy, the risks and benefits must be weighed carefully. The benefits of treatment appear to be most pronounced in cases with high maternal viremia; in such instances, treatment should be considered and discussed with the patient at the start of the third trimester. Viable treatment choices are limited to lamivudine, tenofovir, and telbivudine. Of these, lamivudine and tenofovir appear to be the therapeutic options with reasonable human exposure and safety data in pregnancy.

DISCUSSION

William D. Carey, MD: Referring to your case patient, assume that you treat her with tenofovir and her viral load declines. She delivers her baby and then undergoes a thorough workup, including a liver biopsy, that shows no particular liver damage. What would you do?

Tram T. Tran, MD: There are two separate issues: treating the baby and treating the mother. When you’re treating a mother in her third trimester, your goal is to prevent perinatal transmission of HBV. Once the baby is delivered, treated with HBIg, and vaccinated, then your attention turns to the mother. You can then decide based on treatment guidelines and your clinical judgment whether you want to treat the mom.

The period immediately after birth is a time of treatment uncertainty in mothers who choose to breastfeed, because the nucleoside analogues are likely passed in breast milk to some unknown degree, and it’s probably unwise to expose the child this way. In a mother who chooses to breastfeed, I would stop the medication after the delivery, by which time the baby will have received HBIg and the vaccine. When treatment is stopped, you have to think about the potential for a flare; although clinically significant flares are uncommon, the mother should be monitored after stopping treatment. After she stops breastfeeding, you can decide whether to treat her.

Robert G. Gish, MD: What are the effects of tenofovir on bone? Do you talk to your patients about it, and is it an issue during pregnancy or after the baby is delivered?

Dr. Tran: Some data show a decrease in bone mineral density with tenofovir in the human immunodeficiency virus patient population. I definitely talk to my patients about all the potential risks associated with these medicines as, naturally, pregnant women will be very sensitive to any possible risk to their unborn child. Lamiv­udine probably has the safest profile in pregnancy, given its large body of human experience; however, it is now classified as an FDA pregnancy risk category C drug, whereas tenofovir is classified as category B. This may make a difference to some clinicians.

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