Hepatitis

Hepatitis B and pregnancy

Authors Section Editors Deputy Editor

Hannah Lee, MD Rafael Esteban, MD Jennifer Mitty, MD, MPH Anna SF Lok, MD Louise Wilkins-Haug, MD, PhD

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Apr 2014. | This topic last updated: Feb 01, 2013.

INTRODUCTION — Hepatitis B during pregnancy presents with unique management issues for both the mother and fetus. These include the effects of HBV on maternal and fetal health, the effects of pregnancy on the course of HBV infection, treatment of HBV during pregnancy, and prevention of perinatal transmission. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for approximately one-half of chronic infection worldwide. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection".)

The risk of developing chronic HBV infection is inversely proportional to the age at time of exposure. The risk is as high as 90 percent in those exposed at birth, while the risk is much lower (about 20 to 30 percent) in those exposed during childhood. Maternal screening programs and universal vaccination have significantly reduced transmission rates. Identification of at-risk mothers permits prophylaxis against transmission, which can reduce transmission rates from 90 percent to as low as 5 to 10 percent. Methods of prophylaxis and risk factors for transmission despite prophylaxis are described further below.

IMPLICATIONS OF HBV INFECTION FOR THE MOTHER

Effect on pregnancy outcomes

Acute HBV — Acute viral hepatitis is the most common cause of jaundice in pregnancy [1]. Other causes include acute liver diseases associated with pregnancy such as acute fatty liver of pregnancy, HELLP, and intrahepatic cholestasis of pregnancy (see appropriate topic reviews).

Acute HBV infection during pregnancy is usually not severe and is not associated with increased mortality or teratogenicity [1,2]. Thus, infection during gestation should not prompt consideration of termination of the pregnancy. However, there have been reports of an increased incidence of low birth weight and prematurity in infants born to mothers with acute HBV infection [2,3]. Furthermore, acute HBV occurring early in the pregnancy has been associated with a 10 percent perinatal transmission rate [3]. Transmission rates significantly increase if acute infection occurs at or near the time of delivery, with rates reported as high as 60 percent [1].

Treatment of acute infection during pregnancy is mainly supportive. Liver biochemical tests and prothrombin time should be monitored. Antiviral therapy is usually unnecessary, except in women who have acute liver failure or protracted severe hepatitis [4]. (See "Clinical manifestations and natural history of hepatitis B virus infection", section on 'Acute hepatitis'.) In this setting, lamivudine (100 mg daily) is a reasonable option since it has been used safely during pregnancy and the anticipated duration of treatment is short [5]. Telbivudine or tenofovir (both considered pregnancy class B drugs by the US Food and Drug Administration [FDA]) are acceptable alternatives.

(See 'Antiviral therapy during pregnancy' below.)

Chronic HBV — Pregnancy is generally well-tolerated by women with chronic hepatitis B infection who do not have advanced liver disease. However, because occasional patients develop a hepatitis flare, HBsAg-positive mothers should be monitored closely. We obtain liver biochemical tests every three months during pregnancy and for six months postpartum. HBV DNA should be tested concurrently or when there is ALT elevation.

There are no established associations between chronic HBV and the development of other diseases during pregnancy. Possible associations have been described between chronic HBV and gestational diabetes mellitus [6,7]. However, data are mixed and conflicting [8,9], and the strength of these associations is unclear.

Pregnancy is considered to be an immune tolerant state and is associated with high levels of adrenal

corticosteroids with modulation of cytokines involving the immune response. This has the potential to increase HBV viremia, although most studies have found that HBV DNA levels remain stable during pregnancy [10,11]. ALT levels tend to increase late in pregnancy and in the post-partum period in women with chronic HBV infection. (See "Immunology of the maternal-fetal interface".)

The immunological changes during pregnancy and postpartum have been associated with hepatitis flares (including hepatic decompensation), although flares (particularly those with serious clinical sequelae) appear to be uncommon

[12]. In the postpartum period, flares may be related to immune reconstitution, a situation immunologically analogous to flares that have been described following the withdrawal of corticosteroids in nonpregnant patients with chronic HBV [13-15]. Predictors of HBV flares during pregnancy have not been established.

Flares have been associated with HBeAg seroconversion in approximately 12 to 17 percent of patients [13], a rate similar to what has been described in patients who are not pregnant. Predictors of HBeAg seroconversion in patients who develop a flare remain uncertain. Limited evidence suggests that seroconversion is unrelated to maternal age, parity, or the presence of precore or basal core promotor mutations [13,16].

Effect of pregnancy on liver disease — Immunologic, metabolic, and hemodynamic changes that occur during pregnancy have the potential to worsen or unmask underlying liver disease. Assessment of the severity of liver disease can be difficult during pregnancy because of normal physiologic changes that can mimic clinical features of chronic liver disease. In particular, serum albumin and hematocrit often decrease, while alkaline phosphatase and alpha fetoprotein increase. Similarly, physical examination may reveal findings suggestive of stigmata of chronic liver disease such as palmar erythema, lower extremity edema, and spider angioma.

Pregnancy in patients with advanced cirrhosis is unusual since such patients typically have decreased fertility due to anovulatory cycles. Pregnancy is more likely in those with early cirrhosis. It is important to identify and monitor such patients since they are at significant risk for perinatal complications and poor maternal and fetal outcomes including intrauterine growth restriction, intrauterine infection, premature

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