Editor’s Note: China is a high-incidence country for hepatitis B virus (HBV), with mother-to-child transmission being a significant route of HBV infection in children. If infected with HBV, 15% to 25% of children may develop into chronic carriers, posing risks of liver cirrhosis and liver cancer. Therefore, understanding the epidemiological characteristics of the disease and taking timely and effective treatment measures are of great practical significance. From November 17-19, 2023, the “15th Chronic Viral Hepatitis Antiviral Treatment Challenges and Hot Topics Academic Conference” was grandly held in Chongqing. It was hosted by the Chinese Medical Journal Company Ltd., organized by the Editorial Office of the Chinese Journal of Hepatology, and co-organized by the Hepatitis Group of the Chinese Society of Hepatology, the Second Affiliated Hospital of Chongqing Medical University, and the Chongqing Medical University Institute of Viral Hepatitis. At the conference, Dr. Junliang Fu of the Fifth Medical Center of the Chinese People’s Liberation Army General Hospital sparked intense interest with his thematic discussion on hot issues in pediatric HBV clinical treatment. We are honored to have Dr. Junliang Fu for an in-depth interview, the contents of which are compiled here for our readers.
“Hepatology Digest”: Regarding the timing of treatment for pediatric HBV, should it be immediate, or should treatment wait until ALT levels increase?
Dr. Junliang Fu: The core issue in pediatric HBV treatment currently revolves around whether to treat when transaminase levels are normal or to wait until they rise. We need to consider the efficacy and safety in children, as well as long-term risks of disease progression.
From the current data, the oral antiviral drugs available for children, including lamivudine, tenofovir, and entecavir, all show good safety profiles. Additionally, interferon therapy (including standard and long-acting interferons), although having more side effects, tends to be better tolerated in children than adults. Current data also indicate that interferon therapy poses less risk of adversely affecting children’s growth and development in the long term and further reduces the risk of HBV-induced disease progression. Therefore, from a safety perspective, interferon therapy is also a viable option.
Although current data, including some real-world studies with relatively small sample sizes, are limited, the results are consistent: whether transaminase levels are elevated or normal, earlier treatment leads to better outcomes, including viral suppression, HBeAg seroconversion, and clearance of HBsAg, resulting in more ideal clinical cure rates in children. Thus, the current principle leans towards early treatment, but this cannot be generalized. Clinically, the overall condition of the child, virus replication level and its dynamics, drug accessibility, patient treatment willingness, and socioeconomic factors must all be considered.
“Hepatology Digest”: Regarding drug selection for pediatric HBV, should interferon therapy or nucleoside (acid) analogues be chosen?
Dr. Junliang Fu: First, we must consider the drug indications themselves. According to current guidelines and real-world study data, drugs available for pediatric HBV treatment include lamivudine, which can be used from birth, tenofovir and entecavir from two years of age, standard interferon from one year, and long-acting interferon considered after three years. This is based on the drug indications and accessibility.
Secondly, from the perspective of efficacy, early treatment including treatment in the neonatal period with nucleoside (acid) analogues has been very effective. However, if combined with interferon therapy, the efficacy in achieving HBeAg clearance, serological conversion, and HBsAg clearance is significantly superior to monotherapy with either interferon or nucleoside (acid) analogues. Thus, a combination treatment regimen, or an interferon-based combination regimen, may be a better treatment choice. However, we also need to consider the specific circumstances of the child, as interferon therapy has more side effects and long-acting interferon is relatively more expensive. We need to select the treatment regimen based on the specific situation of the child.
“Hepatology Digest”: Is liver biopsy necessary for children with hepatitis B?
Dr. Junliang Fu: From the current data we have, although children with hepatitis B have a shorter duration of infection, the proportion developing inflammation and fibrosis is not low. For younger children, considering safety, liver biopsy can be omitted, and antiviral treatment can be directly administered.
However, given that the evidence for treatment in children is relatively limited, liver biopsy still holds some necessity. On one hand, it helps in assessing long-term treatment efficacy and the progression of fibrosis. On the other hand, if the treatment response is not ideal later, analysis of liver histology and virological markers before treatment may help adjust the treatment plan for better outcomes. Therefore, at this stage, liver biopsy is still somewhat necessary.
“Hepatology Digest”: How should treatment be selected when clinical treatment for pediatric hepatitis B is ineffective?
Dr. Junliang Fu: Currently, antiviral drugs like entecavir and tenofovir are used in children over two years old, and long-acting interferon in children over three. It’s understood that tenofovir alafenamide is being actively explored for its efficacy and safety in antiviral treatment of children under 12 years of age. Hence, in the near future, we will have more drugs available for treating pediatric hepatitis B.
Research on ineffective treatments has primarily focused on adult patients, with fewer studies conducted in the pediatric hepatitis B field, and those conducted have been short-term. Therefore, no better approach has been established yet. However, I believe we can draw from the treatment experiences with adult patients. If a child shows poor treatment response, we can try switching or combining treatments. Also, we hope to conduct more clinical research and exploration related to pediatric hepatitis B in the future, to provide strong evidence-based medical evidence for clinical practice.
“Hepatology Digest”: Future research directions and prospects for pediatric hepatitis B treatment
Dr. Junliang Fu: The four issues we discussed earlier are the most critical for patients and clinicians, and are the most directly considered in clinical practice. However, behind these issues lie deeper ones that require in-depth research, such as the mechanisms of HBV disease progression, including immunological, virological, and pathological mechanisms, and the natural history characteristics of pediatric hepatitis B, such as the proportions of children in immune-tolerant and immune-clearance phases, and the risks posed by virus carriage. Additionally, current guidelines and consensus are unclear about whether and how to treat children in the immune-tolerant phase. These are also the directions we need to focus on in future research. Only by mastering this information and data can we help develop better treatment strategies.
“Hepatology Digest”: Could you discuss the further updates to China’s pediatric hepatitis B treatment guidelines?
Dr. Junliang Fu: Our latest 2022 hepatitis B prevention and treatment guidelines have significantly changed the recommendations for antiviral treatment of pediatric hepatitis B compared to previous guidelines, including major international ones. For children with normal transaminase levels but histological evidence of inflammation greater than grade one, treatment is advised. For younger children (1-7 years old), even in the absence of histological evidence, treatment is recommended based on existing evidence-based medical evidence. This is a major change in the current guidelines. However, due to the insufficient and not very high level of current evidence-based medical evidence, future larger-scale, multi-center real-world studies and randomized controlled trials are still needed to further validate these areas, thereby promoting the updating and progress of China’s guidelines and expert consensus.
