Hepatitis B and pregnancy

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

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SUMMARY AND RECOMMENDATIONS

• 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.

• Acute HBV infection during pregnancy is usually not severe and is not associated with increased mortality or teratogenicity. (See 'Acute HBV' above.)

• 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. (See 'Chronic HBV' above.)

• Various factors need to be considered when deciding on antiviral therapy during pregnancy including the indications, anticipated duration of therapy, potential adverse effects to the fetus, efficacy, and the risk of the development of drug resistance. The health of the mother and fetus must be considered independently when deciding on treatment. The safety of medication exposure in the fetus needs to be weighed against the risk of stopping or changing therapy for the mother. (See 'Antiviral therapy in women with childbearing potential' above.)

• The infection rate among infants born to HBeAg-positive mothers who do not receive any form of prophylaxis is as high as 90 percent. The high protective efficacy (95 percent) of neonatal vaccination suggests that most infections occur at birth when maternal secretions in the birth canal come in contact with the infant's mucosal membranes. (See 'Perinatal transmission'above.) The most important risk factors for transmission despite prophylaxis appear to be active viral replication and a high maternal HBV viral load. (See 'HBV replicative status' above.)

• Testing for HBsAg should be performed on all women at the first prenatal visit and repeated late in pregnancy in those at high risk for HBV infection. Newborns of carrier mothers should receive passive-active immunization. (See "Standard immunizations for children and adolescents", section on 'Hepatitis B vaccine' .) In addition to standard passive-active immunization, we suggest antiviral therapy be offered to mothers with high HBV DNA levels since it can further reduce the risk of perinatal transmission ( Grade 2B ) ( algorithm 1 ). (See 'Prevention of perinatal transmission' above.)

REFERENCES

DNA-guided hepatitis B treatment, viral load is essential, but not sufficient

Abstract

Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CHB) are at increased risk of developing liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CHB who are hepatitis B e antigen (HBeAg)-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAg-negative CHB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CHB.

Keywords: Hepatitis B virus, Viral DNA, Alanine transaminase, Antiviral drug, Hepatitis B e antigen, Antiviral drug resistance

INTRODUCTION

Hepatitis B virus (HBV) infection is a global public health problem. An estimated 350 million people worldwide are chronically infected with HBV. Approximately 500 000 die annually from HBV-related liver disease[1]. The prevalence and concerns to public health institutions about HBV infection vary according to geographical origin.

Individuals with chronic hepatitis B (CHB) are at increased risk of developing serious problems including liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma (HCC). Fifteen to forty percent of these individuals will develop serious sequelae during their lifetime and have greater evolution to cirrhosis or HCC[2,3]. The 5-year rate of progression from CHB to cirrhosis is estimated to be 12%-20%[4–7]. In patients with cirrhosis, the 5-year cumulative risk of developing HCC is 17% in East Asia and 10% in Western Europe and the United States, and the 5-year liver-related death rate is 15% in Europe and 14% in East Asia[8,9]. Seropositivity for the hepatitis B surface antigen (HBsAg) is one of the most important risk factors for HCC[10]. Seropositivity for hepatitis B e antigen (HBeAg) is associated with an increased risk for HCC, and it is significant regardless of serum level of alanine aminotransferase (ALT) and status of liver cirrhosis[8,10,11]. The risk of progression appears to be greatest in patients who progress from an immunotolerant to an immune-clearance phase[12], in patients who have delayed HBeAg seroconversion[13], and in patients who have reactivation of HBV replication after HBeAg seroconversion[14–16].

Disease progression is variable and multifactorial. It is influenced by several factors including replicating activity of the virus, and host and environmental factors[17]. Four phases of CHB have been defined: immunotolerant phase, immune active phase, HBeAg seroconversion to anti-HBeAg, and inactive carrier.