Hepatitis B virus (HBV) infection remains a global public health problem [1]. Chronic HBV infection can increase the risk of liver cirrhosis and hepatocellular carcinoma [2,3]. The World Health Organization (WHO)’s goal of eliminating hepatitis B by 2030 necessitates an urgent need for efficacious antiviral strategies. Mother-to-child transmission of HBV accounts for the majority of cases with chronic hepatitis B (CHB) [4]. More than 80% of infants who are vertically infected develop CHB, whereas only 5% of adults who acquire HBV become chronically infected [5,6]. Therefore, it is of paramount importance to manage HBV infection in childhood, which has a direct and significant impact on the WHO’s goal achievement, especially in areas of the world with a prevalence of HBV.

According to current guidelines, antivirals for paediatric CHB patients include interferon-α (IFN) and nucleos(t)ide analogues (NA) [[7], [8], [9], [10]]. In this special population, IFN therapy remains the important treatment strategy of choice for individuals with elevated alanine aminotransferase (ALT) levels, as seroconversion from hepatitis B surface antigen (HBsAg) to anti-HBs is the main aim [7]. However, till date, there have been few studies suggesting an optimal strategy among different IFN-based antiviral therapies (e.g. IFN monotherapy, IFNNA sequential therapy, de novo IFN and NA combination therapy) in children with CHB. Reasons mainly include great difficulties in performing paediatric clinical trials to compare the efficacy of different antiviral regimens. To tackle the limitations, we collected real-world data through electronic medical records to study the efficacy of different IFN-based antiviral strategies in CHB children, with the aim of providing evidence to guide optimal clinical care for the population.