Clinical Course and Outcomes of Paediatric Chronic Hepatitis B: Insights From a Multicenter Longitudinal Cohort of 248 Patients

Chronic hepatitis B virus (HBV) infection in children remains a dynamic condition with an incompletely defined natural history. We conducted a multicenter, retrospective cohort study across six Italian paediatric centers to characterize disease progression, evaluate the applicability of adult-derived classification systems, and identify predictors of HBeAg seroconversion. Children aged 0-18 years with chronic HBV diagnosed between January 2006 and August 2024 were included. The primary outcome was spontaneous HBeAg seroconversion, while secondary outcomes included the applicability of the 2017 EASL phase classification and the characterization of children requiring antiviral therapy. Of 248 children included, 45% were unclassifiable by 2017 EASL criteria at baseline. HBeAg seroconversion occurred in 129 children (52%): 34 (26%) were HBeAg-negative at baseline and 95 (74%) seroconverted during follow-up. Higher baseline ALT levels were significantly associated with seroconversion (p < 0.001), whereas HBV DNA levels were not. Seroconversion was less frequent among children of Asian origin (p < 0.001). Fourteen children (6%) received antiviral therapy with 50% achieving seroconversion; all treatments were well tolerated. Applying 2024 WHO guidelines retrospectively, 81 children (33%) would have met treatment criteria. Despite this, most children were not treated, reflecting a cautious clinical approach that may be justified by the high rates of spontaneous viral control. These findings underscore the limitations of adult-derived classification systems in paediatric populations and highlight the need for paediatric-specific management frameworks and prospective studies to optimize treatment strategies.