Chronic hepatitis B virus (HBV)
infection in endemic areas usually starts since infancy and early childhood and persists lifelong. The
clinical course varies among different chronic infected subjects. Majority of chronic HBV infected children present with immune-tolerant status initially, experience the immune clearance phase with various degree of liver injury during or beyond puberty, and then enter the inactive phase after
hepatitis B e antigen (
HBeAg) seroconversion. Part of them may have HBV
DNA titers elevation with
hepatitis flare after
HBeAg seroconversion, the so call
HBeAg-negative
hepatitis flare.
Liver cirrhosis, and even
hepatocellular carcinoma may develop afterward.The complex course of chronic HBV
infection is associated with the age/route of viral acquisition, host factors such as immune and endocrine factors, viral factors, and host-viral interactions. The adrenarche and puberty onset modulate the start of immune clearance and the severity of liver
inflammation in chronic HBV infected children. The genotype and phenotype of human
cytokines, innate immunity, and
human leukocyte antigens are also associated with the onset of immune clearance of HBV and severity of
inflammation. Immune escape HBV mutant strains, emerged during the immune clearance phase under host immune surveillance, may cause different impacts on viral biosynthesis, host immune responses, and
clinical course.Early events in childhood during chronic HBV
infection may serve as important predictors for the later outcome in adulthood. Understanding the mechanisms triggering liver
inflammation and their long-term impacts may enhance the development of better and earlier therapeutic strategies for patients with chronic HBV
infection.