Evaluation and Management of Hepatitis B in Pregnancy: A Survey of Current Practices

Chronic hepatitis B virus (HBV) affects up to 400 million individuals worldwide.1 It is estimated that 1.25 million individuals in the United States are chronically infected.2,3 Up to 15–40% of individuals with chronic HBV die prematurely from cirrhosis or hepatocellular carcinoma.4 Worldwide, vertical transmission remains the most frequent route of infection, particularly in endemic areas where up to 20% of women of childbearing age may have HBV. These women constitute a reservoir for perinatal transmission, which is associated with a very high rate of chronicity (up to 90%).5–7 Even with the use of appropriate prophylaxis with HBV immunoglobulin (HBIG) and HBV vaccination, a significant risk of vertical transmission remains, particularly in mothers with high viral loads and positive hepatitis B e antigen (HBeAg) status. An HBV DNA level greater than 107 genome equivalents/mL is a risk factor for HBV transmission.8,9 Given the correlation between high HBV DNA levels and the risk of vertical transmission, investigators have studied the use of antivirals to prevent HBV transmission. However, data on the safety and efficacy of antiviral treatment of HBV in pregnancy remain limited. Currently, the US Food and Drug Administration lists telbivudine (Tyzeka, Novartis) and tenofovir (Viread, Gilead) as pregnancy category B drugs. Lamivudine (Epivir, Glaxo-SmithKline), entecavir (Baraclude, Bristol-Myers Squibb), adefovir (Hepsera, Gilead), and emtricitabine (Emtriva, Gilead) are listed as pregnancy category C drugs. Lamivudine has been the most extensively studied antiviral agent in pregnant patients. A report of 38 women with chronic HBV who became pregnant while on lamivudine revealed that none of their babies were hepatitis B surface antigen (HBsAg)-positive at 1 year compared to 26% of historical controls.10 Lamivudine treatment of HBV in pregnancy was also associated with a reduction in both maternal and fetal complications. A study of 8 women who were HBeAg-positive with a high HBV DNA level (>1.2 × 109 genome equivalents/mL) treated with lamivudine during the last 4 weeks of pregnancy revealed that 1 of 8 (12.5%) of the babies was HBsAg-positive at 1 year compared to 7 of 25 (28%) historical controls.11 A randomized, double-blind, placebo-controlled, clinical trial reported that lamivudine treatment during the last 8 weeks of pregnancy reduced vertical transmission compared to HBIG and HBV vaccination alone.12 However, this study was notable for a high (39%) rate of vertical transmission despite HBIG and HBV vaccination. Finally, a case report of vertical transmission despite long-term maternal lamivudine treatment with undetectable HBV DNA levels suggested a persistent risk of vertical transmission despite lamivudine treatment.13 None of these studies reported an increase in maternal or fetal adverse events with lamivudine. Although tenofovir and telbivudine are listed as pregnancy category B drugs, there have been no published studies using these drugs in pregnant women with HBV. There have also been no other published studies using entecavir, adefovir, or emtricitabine for preventing HBV vertical transmission. In the absence of conclusive data, the optimal approach to the management of these patients is unclear. The Centers for Disease Control and Prevention and the American Association for the Study of Liver Diseases (AASLD) have not made any specific recommendations for antiviral treatment of pregnant women with HBV.14,15 The HBV treatment algorithms from Keeffe and colleagues published in 2006 and 2008 recommended individualization of therapy for pregnant HBV patients.16,17 There has been no previous survey on the practice patterns of physicians for managing pregnant patients with HBV. Due to the absence of robust data and specific treatment guidelines, we postulated that there would be significant heterogeneity in managing these patients. Accordingly, we sought to evaluate the practice patterns of physicians with regard to HBV evaluation and management in pregnant women. In addition, we sought to determine the heterogeneity of these practice patterns by primary specialty and practice description. We thought that identification of practice patterns and evaluation of their heterogeneity could guide and highlight the need for further research, lead to the strengthening of guidelines, and improve education of physicians regarding the management of this challenging patient population.