Background and AimsHepatitis B surface antigen (HBsAg) clearance is significantly more common in children with chronic hepatitis B (CHB) than in adults; however, the possible influencing factors related to HBsAg loss have yet to be found. This study aimed to explore the efficacy of long-term interferon (IFN)α therapy in treating children with CHB and analyzed the factors influencing functional cure after treatment.MethodsA total of 236 children aged 1–6 years and diagnosed with CHB via liver biopsy were included in the study, all receiving IFNα treatment (IFNα-2b monotherapy, IFNα-2b followed by lamivudine [LAM] or IFNα-2b combined with LAM) and followed up for 144 weeks. A comprehensive analysis was conducted on clinical data, including biochemical items, serum markers of hepatitis B virus (HBV) and immunological indexes, and logistic regression analysis was used to screen the influencing factors related to HBsAg loss.ResultsThe cumulative loss rates of HBsAg were 79.5%, 62.1% and 42.1% at 144 weeks after the start of treatment in the 1–3 years-old group, 3–5 years-old group and 5–7 years-old group, respectively (p<0.05). IFNα-2b combined with LAM treatment displayed the highest HBsAg loss rates compared with monotherapy and sequential treatment (p=0.011). Younger baseline age and lower HBsAg levels were independent factors for the prediction of HBsAg loss (p<0.05). The baseline PreS1 and hepatitis B core antibody levels in the HBsAg loss group were lower than those in the HBsAg non-loss group. In addition, the PreS1 level was positively corelated with the level of HBsAg, HBV DNA and liver inflammation.ConclusionsLong-term treatment with IFNα was effective in achieving HBsAg loss in CHB children aged 1–6 years-old. Age less than 3 years-old and lower HBsAg levels are independent predictors of functional cure in children with CHB.