Hepatitis B virus infection in children

Abstract

For two decades, hepatitis B vaccine has been integrated into national routine childhood vaccination programs in almost all countries. The prevalence of HBsAg has decreased in children worldwide. However, there are children who miss the benefit of hepatitis B vaccine in some regions and countries. Long-term follow-up studies have revealed the clinical outcomes of chronic hepatitis B virus infection in children. A small percentage of chronically infected children develop liver cirrhosis and hepatocellular carcinoma. However, it is controversial who should be treated and when antiviral treatment should be initiated in children. Compared with adult studies, the data are insufficient to evaluate the pathogenesis of hepatitis B infection and the efficacy of antiviral treatment in childhood. New antiviral drugs have been approved for children and adults. Also, oral antiviral drugs are administered to pregnant women to reduce the hepatitis B virus mother-to-child transmission rate.

Keywords:

• chronic hepatitis
• cirrhosis
• HBeAg
• HBsAg
• HBV
• hepatocellular carcinoma
• IFN
• mother to child
• nucleoside analogue
• vaccine

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A universal hepatitis B (HB) vaccine plays a central role in the eradication of HBV infection. As of 2012, 94% (183/194) of WHO member states have integrated the HB vaccine into their routine vaccination schedules and 79% of children have received the HB vaccine.

• As of 2012, 48% (94/194) of WHO member states have introduced the HB birth dose. Because it is thought that HBV in Africa is almost always acquired in early childhood via horizontal transmission rather than vertical transmission, a birth dose is not used.

• The prevalence of HBsAg has declined in children worldwide, particularly in southeast Asia. The next step in the universal vaccination strategy is the improvement of routine protocols. For instance, the timeliness of vaccine administration and serological surveys to assess the efficacy of the HB vaccine are needed.

• Long-term follow-up studies of children with chronic HBV infection have been reported. However, there were no significant differences in the cumulative HBeAg seroconversion rate between treated and untreated groups in the studies.

• The frequencies of cirrhosis and hepatocellular carcinoma (HCC) in children with chronic HBV infection range from 0.2 to 3.8% and from 0 to 1.5% during the follow-up period, respectively.

• The decision to initiate antiviral treatment is based on serum alanine aminotransferase (ALT) levels, serum HBV DNA levels and liver histology. Children who are 1 year of age or older with persistent HBsAg for 6 months or more are monitored and evaluated for treatment of chronic HBV infection.

• Regardless of HBeAg positivity, three factors – persistent elevation of ALT levels, high levels of serum HBV DNA, and moderate/severe inflammation and/or fibrosis in liver histology – are important in the consideration of treatment.

• The goal of antiviral treatment is the reduction of HBV replication, ALT level normalization and the improvement of histologic findings. However, the capacity of antiviral treatment to prevent HCC in children has not been proven.

• Conventional IFN-α and four nucleos(t)ide analogues (lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate and entecavir) are approved for the treatment of pediatric patients. Polyethylene glycol-IFN has not yet been approved for children. Except for children with decompensated cirrhosis, IFN-α is the first-line treatment for chronic HBV infection of children.

• Tenofovir (≥12 years of age) and lamivudine (<12 years of age) are recommended for children with decompensated cirrhosis. Entecavir was approved for children of age 2 years or older in 2014. Instead of lamivudine, entecavir should first be administered to children below 12 years of age in view of the high genetic barrier to drug resistance.

• There is a socioeconomic barrier to antiviral treatment worldwide. The drug choice should be individualized based on the disease severity, affordable price of treatment, side effects and drug resistance profile. When entecavir and tenofovir are not available in resource-constrained settings, the combination of adefovir + lamivudine or adefovir + telbivudine is recommended.

• Treatment with nucleos(t)ide analogues in the third trimester will become an available option when pregnant women with high viral loads wish to reduce the risk of mother-to-child transmission.