Director, Clinical Hepatology Research
Department of Liver Transplantation
California Pacific Medical Center
San Francisco, California
Natalie H. Bzowej, MD, PhD, has disclosed that she has received consulting fees from Gilead Sciences and funds for research support from Allergan, Cirius Therapeutics, and Gilead Sciences.
Deciding when to start HBV treatment for a woman of childbearing age depends on the severity of liver disease and, if she is not already pregnant, when she plans to conceive. Here is how I select the optimal HBV therapy for women who are planning to become pregnant or are already pregnant.
HBV Therapy in Women of Childbearing Age
For women of childbearing age who need antivirals for HBV treatment, I recommend discussing pregnancy issues before starting treatment. If the patient is planning to conceive soon, and she has minimal liver disease, it might make sense to delay therapy until after delivery.
If she is not planning to conceive soon, there are several options with varying treatment lengths. Although not recommended for pregnant women, if she is not pregnant, peginterferon can be given for a defined period of 48 weeks. This treatment often results in clinical remission with HBeAg seroconversion.
Oral antivirals usually require longer-term therapy and have lower rates of HBeAg seroconversion. Among the oral antivirals, I consider tenofovir disoproxil fumarate (TDF) an ideal choice because of its efficacy and high barrier to resistance and because—although no HBV antiviral is approved by the FDA in pregnancy—safety data in pregnancy are available for TDF. Safety data in pregnancy are important even in nonpregnant women because not all pregnancies are planned. By contrast, we currently lack data on the safety profile of tenofovir alafenamide (TAF) or entecavir in pregnancy. And although lamivudine and telbivudine are also considered safe in pregnancy, long-term use has a high risk of antiviral resistance, and resistance with short-term lamivudine in the third trimester has been reported
Newly Diagnosed Chronic HBV in Pregnancy
For pregnant women newly diagnosed with HBV early in pregnancy, American Association for the Study of Liver Diseases guidelines recommend treatment if there is risk of hepatic decompensation. In such cases, TDF is also the best choice based on its efficacy and safety data in pregnancy.
However, many women will have mild disease and be in the immune-tolerant phase of HBV infection. Thus, treatment can often be postponed until after delivery.
Continuing HBV Therapy in Early Pregnancy
Because no HBV antiviral is approved by the FDA for use in pregnancy, we face a dilemma when a woman already receiving HBV therapy becomes pregnant: Should she continue or stop her therapy?
Regarding fetal health, the major concern is the risk of exposure to medication during early embryogenesis. Regarding the woman’s health, the major issue is whether interrupting antiviral therapy will harm short-term and long-term liver outcomes. In my practice, if the woman has advanced fibrosis, I continue therapy because interrupting therapy could put her at risk of developing a flare leading to decompensation—which could also affect the fetus.
When continuing therapy during pregnancy, the dilemma becomes whether to switch to a “safer” agent if the woman is not already receiving TDF. Because we lack safety data for entecavir and TAF, I would consider switching such a patient to TDF.
Preventing Perinatal Transmission
Another consideration is preventing perinatal transmission of HBV infection, which can often be achieved after delivery by giving the newborn both passive immunization with hepatitis B immunoglobulin (HBIG) and immunization with the HBV vaccine. However, almost all vaccine and HBIG failures occur when the mother has very high HBV DNA levels.
For handling these cases, data indicate that treatment in the third trimester helps prevent perinatal transmission. Thus, if a pregnant woman has an HBV DNA of > 200,000 IU/mL, HBV treatment should be considered and initiated toward the end of the second trimester. Women with lower HBV DNA levels and no standard indications do not need treatment.
In Clinical Care Option’s decision support tool for first-line HBV therapy, you can see how other experts and I selected first-line HBV therapy for patients planning pregnancy and for a variety of patient scenarios.
When do you recommend starting therapy for your patients planning to become pregnant? Which treatments do you recommend? I encourage readers to share their experiences below.