Global perspectives on chronic hepatitis B management in children and adolescents

touchENDOCRINOLOGY coverage of EASL 2026

Could you give us a brief overview of the current management paradigm for chronic hepatitis B in children and young adults, and why the question of whether to treat early or continue observation remains controversial?

In general, the treatment principles follow the adult liver society guidelines. Anyone with a viral load above 2,000 IU/mL is universally considered for treatment, but additional risk factors for hepatocellular carcinoma (HCC), the most common form of liver cancer, are usually needed to establish treatment candidacy. These include high liver enzymes, a family history of HCC, significant liver fibrosis, or comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD).

For children, particularly very young children, one caveat is that not all drugs are approved for use at a young age. Among the current nucleos(t)ide analogues, entecavir is approved for children aged 2 years and older, tenofovir alafenamide (TAF) for those aged 6 years and older, and tenofovir disoproxil fumarate (TDF) for those aged 12 years and older. Pegylated interferon alfa is approved for children aged 3 years and above. Therefore, children younger than these age thresholds are generally not considered for treatment because the available therapies have not been approved for that age group.

The controversy around treating young people stems from a longstanding misconception that they are at low risk, including low risk for HCC. Traditionally, these patients have been described as being in the “immune-tolerant” phase, meaning they have very high viral loads but normal ALT levels. It was thought that because ALT is normal, the virus is not causing damage. However, this is not entirely true, because ALT is not a perfect marker of liver inflammation.

We now know that HBV DNA can integrate into the host genome at a very early stage of infection, regardless of ALT levels. As a result, the field is moving away from relying solely on ALT and is becoming more open to treating younger patients.

On the other hand, if we treat these patients early, most will need to remain on antiviral therapy long term because they are so young and often have high levels of viral antigen. It may take decades for them to achieve undetectable hepatitis B surface antigen levels. This raises important considerations regarding treatment costs, adherence and potential adverse effects.
These are the key factors that need to be weighed when considering treatment in young people.

What is currently understood about the pathogenesis and immune dynamics of chronic hepatitis B acquired in childhood, and how does this influence decisions around timing of treatment?

For hepatitis B infection, I would say that the age at exposure is the most important determinant of chronicity. If exposure occurs before the age of 5 years, or even at birth, the risk of developing chronic infection is very high. In contrast, if exposure occurs after the age of 5 years or in adulthood, most people will not develop chronic infection.

In fact, around 90% of the existing pool of chronic hepatitis B infections originates from mother-to-child transmission. The reason for this is that, during infancy and early childhood, the immune system is not yet mature enough to mount an effective immune response to control the virus. Hepatitis B virus itself is also a stealth virus; it does not induce robust inflammation or strong pro-inflammatory and antiviral cytokine responses. In addition, the virus has multiple mechanisms to evade host immunity.

When considering treatment in very young patients, another important factor is that they may not have a sufficiently developed immune response to mount an effective attack against the virus, even when viral replication is suppressed with antiviral therapy. Therefore, decisions around treatment timing involve a delicate balance between viral suppression and the host’s ability to generate an effective immune response.

Ultimately, chronic hepatitis B reflects a complex interaction between the virus and the host immune system, and this interaction is a key consideration when deciding whether to initiate treatment early or continue observation.

What factors should clinicians consider when deciding whether to initiate antiviral therapy in children and adolescents with chronic hepatitis B rather than adopting a watch-and-wait approach?

The less controversial factors include liver enzymes and fibrosis. ALT is the most commonly used liver enzyme and is generally considered a good biomarker of liver inflammation. Fibrosis is another important consideration. If either of these is abnormal, then antiviral therapy should be considered.

There are also increasingly recognized risk factors, such as a family history of liver cancer or cirrhosis and, as mentioned earlier, comorbidities. If a patient has hepatitis B together with diabetes or fatty liver disease, these conditions can further increase the risk of liver cancer.

There are still important research gaps in this area. With current risk stratification approaches, we are not able to identify all patients who are at increased risk. We do have risk scores, calculators and established risk factors, but we still lack reliable biomarkers, particularly for young patients. We know that many of these patients are young, have high viral loads and normal ALT levels, but we do not have a good way to measure the extent of viral integration within the liver. We also cannot accurately predict which young patients are most likely to develop liver cancer at a young age.

These limitations make treatment decisions more challenging and highlight the need for better biomarkers and more precise risk prediction tools in pediatric and adolescent hepatitis B.

Your session highlights global perspectives on HBV management. What are some of the key differences in approaches between regions, particularly in relation to perinatal management and treatment thresholds in younger populations?

I would say the most striking differences relate to the use of hepatitis B immunoglobulin (HBIG) and birth-dose vaccination. According to the most recent Global Hepatitis Report published last month, some countries still do not have national strategies in place to prevent mother-to-child transmission of hepatitis B.

For example, some countries do not routinely test pregnant women for hepatitis B surface antigen. Others perform screening but do not offer antiviral treatment when indicated. There are also countries that do not recommend HBIG in addition to birth-dose vaccination for infants born to mothers with hepatitis B.

There are also differences in recommendations regarding caesarean section. Some guidelines suggest that women with high viral loads should consider caesarean delivery to reduce the risk of mother-to-child transmission. However, the evidence does not strongly support this approach. Current data suggest there is insufficient evidence to conclude that caesarean section reduces the risk of transmission, and some guidelines therefore recommend against routine caesarean delivery solely for this purpose.

One encouraging area of consistency is breastfeeding. Most guidelines support continued breastfeeding, even when the mother has hepatitis B, because transmission through breast milk is extremely rare. In addition, if the mother is receiving antiviral therapy, this is generally considered safe for the infant.

Beyond these areas, there is still considerable variation between regions. Differences exist in the viral load thresholds used to initiate peripartum antiviral prophylaxis, as well as recommendations regarding when treatment should be started and stopped. These variations can create uncertainty for clinicians and contribute to differences in practice across healthcare systems.

Similar variability also exists in approaches to younger patients with chronic hepatitis B, particularly regarding treatment thresholds and the balance between early intervention and continued observation.

As our understanding of viral integration, immune tolerance, and treatment response evolves, what future trends do you anticipate in the management of hepatitis B in children and young adults?

I would say that, overall, the field is moving towards earlier treatment and lower treatment thresholds. Previously, some guidelines required ALT levels to be at least two times the upper limit of normal before treatment was considered. Now, most guidelines are moving towards a threshold of one time the upper limit of normal, while also incorporating additional criteria that can support treatment decisions.

That said, I think an individualized approach is important because we cannot apply a single overarching principle to every patient. Treatment decisions should take into account each patient’s specific risk factors and clinical circumstances.

Another important area of development will be the identification of more accurate biomarkers for risk prediction and early cancer detection. At present, ultrasound is the recommended method for HCC surveillance, but it is not perfect, with a sensitivity of around 70%. A major challenge is that surveillance remains heavily underutilized. In practice, only around one in two patients with hepatitis B undergoes appropriate surveillance.

We know that ultrasound surveillance can reduce mortality from HCC, so we need to do a better job of ensuring that patients are offered surveillance and reminded to arrange regular ultrasound examinations. This is already proven to provide a survival benefit.

To address the fact that ultrasound is not 100% sensitive, additional biomarkers will likely play a greater role in the future. Some guidelines recommend alpha-fetoprotein, while others include biomarkers such as PIVKA-II. We are also seeing increasing data on cell-free DNA and circulating tumor DNA, which may further improve the accuracy of early HCC detection.

Taken together, I think the future will involve earlier and more personalized treatment strategies, combined with better tools for risk stratification and earlier cancer detection.