Editor’s Note: China is a country with a high incidence of hepatitis B, and mother-to-child transmission is an important route for children in China to contract the hepatitis B virus (HBV). Although chronic HBV infection in childhood rarely progresses to active hepatitis, there is still a risk of developing cirrhosis and liver cancer. Therefore, understanding the epidemiological characteristics of childhood hepatitis B and taking effective prevention and control measures are particularly important to reduce the incidence of childhood hepatitis B in China and promote healthy growth. In recent years, as the goal of clinical cure for hepatitis B has gradually gained more attention, the issue of clinical cure for childhood hepatitis B has also received increasing focus. At the recently concluded “15th Academic Conference on Antiviral Therapy Difficulties and Hotspots in Chronic Viral Hepatitis,” Dr. Fusheng Wang from the Fifth Medical Center of the PLA General Hospital presented a special report on “Treatment and Clinical Cure of Childhood Hepatitis B,” offering an in-depth analysis of these issues. Hepatology Digest invited Dr. Fusheng Wang to share his insights on the topic, and the content is summarized as follows:
“Hepatology Digest”: Could you please start by introducing the clinical characteristics of childhood hepatitis B and its clinical outcomes?
Dr. Fusheng Wang: In fact, compared to adult hepatitis B, clinical research on childhood hepatitis B is relatively scarce, including limited epidemiological data and studies on its natural history. The clinical staging of children infected with HBV is also not yet clear. However, one thing is certain: most chronic HBV infections in China start from perinatal or infantile infection, and the rate of chronicity is generally high.
The term “children” covers a wide range, including newborns, infants, toddlers, preschoolers, school-age children, and adolescents. Each age group has its own characteristics of disease onset. Newly infected children may have acute infections, but the probability is lower than in adults, and the rate of self-recovery is also lower. Additionally, the rate of chronic disease in children infected with HBV varies by age group, and specific data requires further research. Generally, the younger the age, the higher the rate of chronicity. For example, HBV infections occurring in the perinatal period and infancy have a 90% and 25%-30% chance, respectively, of developing into chronic infections, while infections occurring after the age of 5 have only a 5%-10% chance of becoming chronic. If HBV infection persists in the body for a long time, there is a risk of the disease progressing to cirrhosis and liver cancer during the child’s lifetime, and there is currently a lack of systematic clinical research in this area.
Hepatology Digest: Could you please elaborate on why the clinical cure rate for childhood hepatitis B is relatively higher? What useful insights does this finding provide for the clinical treatment strategy of hepatitis B?
Dr. Fusheng Wang: Currently, there is limited research on antiviral treatment for children with HBV infection. However, recent studies have found that age may be an independent factor influencing the effectiveness of antiviral treatment in children. Real-world studies and some randomized controlled trials (RCTs) suggest an important clinical phenomenon: the younger the child, the higher the cure rate of antiviral treatment. This cure refers to a functional cure, meaning a sustained undetectable level of serum HBsAg and HBV DNA, along with HBeAg seroconversion. However, these results are primarily from studies on children with chronic hepatitis B during the immune-active phase, and there is less evidence for children in the immune-tolerant phase. The main limitation of current clinical studies is the unclear clinical staging of children with chronic hepatitis B, which requires further exploration.
Data from a study by the National Center for Infectious Diseases on children in the immune-active phase showed that children aged 1-3 years who received antiviral treatment had an HBsAg clearance rate of up to 65.8%, the rate was 44% for those aged >3-5 years, and 23.8% for the >5-7 years group. These data indicate that younger age is a favorable factor for clinical cure, and the younger the age, the higher the HBsAg clearance rate. However, the exact age at which children have the highest cure rate has not yet been determined. Furthermore, whether treatment is needed for children in the immune-tolerant phase or younger (below 1 year old) after infection, and how to treat them, requires further in-depth research.
Hepatology Digest: Regarding when to initiate treatment for childhood hepatitis B, do you think there is an optimal time for treatment?
Dr. Fusheng Wang: The 2022 version of China’s “Guidelines for the Prevention and Treatment of Chronic Hepatitis B” suggests that children with active chronic hepatitis B or cirrhosis should receive timely antiviral treatment. Therefore, if HBV infection in children, whether acute or chronic (clinically mostly chronic), can be detected early, it is necessary to administer antiviral treatment promptly. This is especially important for younger children, such as those under 3 years old. For these children, the rate of clinical cure is higher. As age increases and the number of infected liver cells grows, along with impaired immune system function, the effectiveness of treatment decreases. Timely treatment at this stage may not be as effective. From this perspective, the younger the age, the more likely a clinical cure can be achieved, so I believe it’s best to screen, diagnose, and start antiviral treatment as early as possible for children at risk of infection.
Hepatology Digest: Could you also introduce the latest advancements in the clinical research of nucleos(t)ide analogs and interferons in treating childhood hepatitis B in recent years?
Dr. Fusheng Wang: Interferons and nucleos(t)ide analogs are currently the first-line drugs for treating chronic hepatitis B. In fact, achieving a clinical cure for hepatitis B using existing drugs is still very challenging for adults. However, for children, especially younger children (below 3 years old), the treatment regimen for chronic hepatitis B is similar to that for adults. The use of first-line drugs may already be sufficient and can largely achieve a functional cure, which is a significant breakthrough.
In recent years, with the progress in hepatitis B treatment, experts and scholars have deepened their understanding of chronic hepatitis B in children. Updates to China’s guidelines for the diagnosis and treatment of chronic hepatitis B often adjust the treatment recommendations for this special group, providing more proactive indications for antiviral treatment of childhood chronic hepatitis B. The latest 2022 guidelines recommend considering antiviral treatment for children aged 1-7 years with positive HBV DNA and normal ALT, even in the absence of liver pathology results, provided there is sufficient communication with guardians and informed consent is obtained. Additionally, the expansion of indications for antiviral treatment, such as emphasizing treatment for patients with low viremia, is also a significant advancement, which will positively impact the clinical diagnosis, treatment, and prognosis of the hepatitis B population.
Hepatology Digest: Regarding the treatment of childhood hepatitis B, are there any other potentially promising treatment methods or strategies?
Dr. Fusheng Wang: Overall, for the treatment of childhood hepatitis B, existing interferon or nucleos(t)ide analog therapies can achieve certain effects, but antiviral drugs have age restrictions for use. In recent years, with the progress in clinical antiviral treatment research for childhood hepatitis B, including exploratory studies conducted by our team, we have obtained more solid theoretical support for the treatment of childhood hepatitis B. At the recently concluded AALSD conference, we saw data on the safety and effectiveness of Tenofovir Alafenamide Fumarate (TAF) in treating children over 6 years old with hepatitis B. Therefore, I believe Chinese scholars should conduct more in-depth clinical research in the area of childhood hepatitis B treatment. For instance, exploring which potent and safe antiviral drugs are available, the effectiveness of antiviral treatment for hepatitis B in younger children (including newborns), and whether drugs like TAF can be used in children under the age of one, are all worthwhile subjects for future research. Additionally, there is currently a lack of guidance on the treatment of acute HBV infections (including both adults and children), but personally, I think that to help children with acute HBV infection achieve the best prognosis, active antiviral treatment should also be considered.
