Updates in the management of hepatitis B in children

ABSTRACT

Introduction: Universal infant hepatitis B virus (HBV) vaccination program has reduced HBV infection dramatically in vaccinated young generations. Management of chronically infected children is still challenging concerning high viral load with mostly mild diseases, yet with a nonnegligible proportion of advanced diseases, and long-term effect of antivirals. However, with more potent antivirals approved for pediatric patients, to start antivirals earlier in eligible patients may benefit their outcomes. This review aimed to update the current management of chronic hepatitis B in children.

Areas covered: This review covered the natural history of chronic HBV infection, management of chronic hepatitis B in children from the past to the present, current consensus on the treatment of chronic hepatitis B in children, controversies in cessation of oral antivirals, and management of special populations such as pregnancy and co-infections.

Expert opinions: Without contraindication, peginterferon is recommended for immune-active children ≥ 3 years old. For those intolerant, decompensating or preferring oral therapy, first-line Nucleos(t)ide analogs (NUC), Entecavir or Tenofovir, may be applied. For immune-tolerant or inactive carriers, close monitoring is crucial. When to stop NUCs and novel therapies for HBV cure await further research.

KEYWORDS:

• Nucleos(t)ide analogs
• pegylated interferon
• HBeAg seroconversion
• HBsAg loss
• reactivation
• liver fibrosis
• immune tolerant
• immune clearance
• HBeAg-negative hepatitis

Article highlights

• Most chronic HBV-infected children are mild in disease severity but a minority of them may progress to fibrosis/cirrhosis or liver cancer without self-awareness. To identify eligible cases for antiviral therapy, screening out chronic carriers, sensible monitoring of the disease status, and communication with the child and the parents about the cost and benefit of antiviral therapy is essential.

• Understanding the natural history of chronic hepatitis B virus infection and the indications, risks, and benefits of current antiviral therapy are critical in decision-making on who and when to treat.

• Current antiviral therapy cannot cure chronic HBV infection. Instead, the goal of anti-HBV therapy is to prevent disease progression to liver failure, cirrhosis or hepatocellular carcinoma.

• Interferon or pegylated interferon is the first-line therapy in chronic hepatitis B children in the immune active phase with high viral load (>20,000IU/mL). The pros are a finite course and no resistance; and the cons are parenteral administration, frequent adverse events, and contraindication in decompensated diseases. The efficacy of one-year therapy is up to 30% in terms of HBeAg seroconversion.

• High genetic barrier nucleos(t)ide analogs (Entecavir and Tenofovir) are first-line oral antivirals for the licensed ages in children. They are well-tolerated and highly potent in viral suppression, but it takes several years to achieve up to 50% HBeAg seroconversion. Relapse rates are high after cessation of therapy. When to stop is a challenging issue to weigh between viral reactivation or host immune clearance to take place.

• Whether the carrier children are managed with or without antivirals, lifetime monitoring, cancer surveillance and prompt intervention are key to prevent poor consequences of advanced diseases or liver cancer.

• Novel therapeutics to target different facets of HBV lifecycle or to enhance HBV-specific host immunity are undertaken to achieve a functional cure or eventually a cure.

Declaration of interest

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.