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Professor of Medicine
Hospital Universitario Vall d'Hebron
Maria Buti, MD, has disclosed that she has received consulting fees from Gilead Sciences.
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The management of HBV infection during pregnancy presents several important challenges. Key issues to consider are the prevention of mother-to-child or vertical transmission of HBV infection and the effects of pregnancy on the natural history of HBV infection and the effects of chronic HBV infection on pregnancy outcomes. In this commentary, I provide my insights specifically on the interplay between HBV infection and pregnancy.
Effects of Pregnancy on the Natural History of HBV infection
One concern with HBV infection during pregnancy is the effect of pregnancy on the natural history of the infection. Chronic HBV infection is characterized by different disease phases defined by HBeAg status, alanine aminotransferase (ALT) levels, HBV DNA levels, and the degree of liver damage.
In my clinic, most pregnant women with chronic HBV infection have healthy livers and are in the disease phase termed hepatitis B surface antigen inactive carrier or HBeAg-negative chronic infection. This phase is defined by HBeAg-negative status (as the name implies), low HBV DNA levels, and normal liver function (normal ALT and no other evidence of liver disease). These cases require no special monitoring during pregnancy.
However, for women with chronic hepatitis B who are pregnant and have advanced liver inflammation and/or fibrosis, antiviral therapy is indicated for their own health. Outside of considerations related to the prevention of vertical HBV transmission, the indications for antiviral therapy initiation in pregnant women are generally the same as those for patients who are not pregnant, and few require treatment because of the presence of liver disease.
For those who do require antiviral therapy for HBV treatment, the recommended antiviral drug is tenofovir disoproxil fumarate (TDF). Women with chronic hepatitis B who are already receiving antiviral therapy when they become pregnant or when they are planning a pregnancy should be switched to TDF if they are not already receiving it. Among the antiviral drugs with high efficacy and high barrier to resistance (entecavir, TDF, and tenofovir alafenamide), TDF has the most safety data during pregnancy.
Pregnancy is considered to be an immune-tolerant state and is associated with high adrenal corticosteroid levels that modulate immune responses. For this reason, mild ALT elevations without clinical sequelae may be observed during pregnancy. During the postpartum period, immune reconstitution may lead to HBV liver flares. Although postpartum HBV flares are more common among women who are HBeAg positive, there are no clear predictors that can identify which women are not at risk. Therefore, guidelines from the AASLD recommend that all pregnant women with HBV infection who are not receiving antiviral therapy—and those who discontinue antiviral therapy at or early after delivery—should be followed carefully for up to 6 months after delivery for hepatitis flares as well as HBeAg seroconversion, which can occur in association with flares.
Effects of Chronic HBV Infection on Pregnancy Outcomes
Chronic HBV infection has no well-established effects on pregnancy or newborn outcomes; however, some studies have observed a possible association between chronic HBV infection and increased risk of premature birth, lower birth weight, and gestational diabetes.
Women with cirrhosis need to be monitored more frequently because they are at significant risk for perinatal complications and poor maternal and fetal outcomes. Medical care for pregnant women with chronic HBV infection should be provided in collaboration with a hepatologist.
In all cases, women with chronic HBV infection who become pregnant should be informed about the risks and benefits of antiviral therapy and the risk of vertical transmission of HBV infection. Those who are not receiving antiviral therapy during pregnancy and the postpartum period should be monitored closely for ALT flares.
What is the most challenging aspect of HBV care for patients who are pregnant in your clinic? Please join the conversation and share your experiences in the comments box.
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