Functional cure, defined as durable hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA titers below the lower limit of detection (LLOD), is associated with better clinical outcomes of chronic HBV infection and is regarded as the preferred treatment endpoint of novel therapeutic agents against HBV.
Scientists from the College of Medicine of National Taiwan University and National Taiwan University Children's Hospital identified that the Hepatitis B e antigen (HBeAg) seroconversion in childhood, high-genetic-barrier nucleos(t)ide analog(s) therapy before HBeAg seroconversion, and the HBsAg titer <1,000 IU/mL after HBeAg seroconversion are predictors of functional cure.
The findings published in the journal Clinical Gastroenterology and Hepatology demonstrate the merit of the follow-up and treatment of chronic HBV infection from childhood.
Traditionally, the clinical course of chronic HBV infection in childhood is considered to be eventless and benign. Previous studies have demonstrated that the treatment of chronic HBV-infected children with lamivudine may increase the late complications of chronic HBV infection in adulthood.
Thus, most clinicians often recommend conservative observation for children with chronic HBV infection. To treat or not to treat chronic HBV-infected children with inflammation remains unclear to date.
HBsAg-loss (below the LLOD) in combination with undetectable HBV DNA (below the LLOD) has been reported to minimize the risk of HCC in adults with chronic HBV infection, and the European Association for the Study of the Liver (EASL)–American Association for the Study of Liver Diseases (AASLD) HBV Conference on Treatment Endpoints altered the treatment goal from simple virological suppression to a "functional cure" of HBV.
In a very long-term follow-up cohort from childhood to adulthood in Taiwan, the scientists recruited 413 chronic HBV-infected patients who were followed from childhood to adulthood for a total of 10,888 person-years in this study.
All of these subjects were followed from HBeAg-positive status and finished their HBeAg-seroconversion during the follow-up period. Prof Mei-Hwei Chang launched the historical cohort more than 35 years ago.
The exciting data showed that HBeAg-seroconversion in childhood (<18 years of age), high-genetic-barrier nucleos(t)ide analog(s) therapy before HBeAg-seroconversion, and a serum HBsAg titer <1,000 IU/mL at 18 months after HBeAg-seroconversion were significant predictors of functional cure of chronic HBV infection.
Prof. Jia-Feng Wu from the College of Medicine of National Taiwan University and National Taiwan University Children's Hospital, and lead author of the study said, "Our previous serial studies showed that the benefit of HBeAg-seroconversion in childhood is associated with fewer basal core promoter gene mutations, and predicting a lower risk of HBeAg-negative hepatitis and liver fibrosis in adulthood."
"In this study, we further demonstrated the benefit of HBeAg-seroconversion in childhood in predicting HBV functional cure. The study further demonstrated that the high-genetic-barrier nucleos(t)ide analog(s) therapy before HBeAg-seroconversion in childhood further benefits the occurrence of HBV functional cure."
The World Health Organization (WHO) has set a goal of treating >80% of patients with chronic viral hepatitis by 2030, and treating or not treating young patients with chronic HBV infection (especially children) is a challenging issue.
The WHO modified its recommendations for the treatment of chronic HBV in 2024, but the current recommendations for chronic HBV-infected children remain insufficient.
The findings of the current study suggest that high-genetic-barrier nucleos(t)ide analog(s) therapy in childhood before HBeAg-seroconversion and HBeAg-seroconversion in childhood have marked benefits in young patients (including children) with chronic HBV infection to achieve functional cure later in life.
More information: Jia-Feng Wu et al, Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study, Clinical Gastroenterology and Hepatology (2024). DOI: 10.1016/j.cgh.2024.07.036
Journal information: Clinical Gastroenterology and Hepatology
Provided by National Taiwan University