HBeAg-seroconversion in childhood among predictors of functional cure of chronic HBV
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Key takeaways:
- The cumulative probability of functional cure was 14.53% at a mean age of 25.75 years.
- The annual cure rate was 0.55% per person-year, which increased to 0.96% per person-year following HBeAg-seroconversion.
Hepatitis B e-antigen seroconversion in childhood and low hepatitis B surface antigen titers after seroconversion independently predicted functional cure in chronic HBV-infected patients followed from childhood through adulthood.
“Functional cure for HBV is currently regarded as a primary endpoint for novel therapeutic agents,” Jia-Feng Wu, MD, MSc, PhD, clinical professor in the department of pediatrics at National Taiwan University Hospital, and colleagues wrote in Clinical Gastroenterology and Hepatology. “The annual HBsAg-seroclearance rate is 0.5% to 2.3% per person-year after hepatitis B e-antigen (HBeAg) seroconversion in children and adults, and the reported predictors of HBsAg loss include a decrease in the serum HBsAg level, a low baseline serum HBsAg level and an early HBeAg-seroconversion.”
They continued: “However, the prevalence and predictors of the novel goal, functional cure of chronic HBV infection, are unclear.”
Thus, Wu and colleagues conducted a retrospective study and prospectively enrolled a pediatric cohort of 413 patients (249 males) with chronic HBV, who received regular follow-ups at a mean age of 7.2 years and underwent HBeAg-seroconversion at a mean age of 17.2 years. The mean duration of follow-up was 26.36 years.
The researchers defined functional HBV cure as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks.
According to results, the cumulative probability of functional cure after 10,888 person-years of follow-up was 14.53% at a mean age of 25.75 years (95% CI, 22.38-29.07). Of those who achieved functional cure, 40% ever received antiviral therapy, while 60% had spontaneous cure. The annual functional cure rate was 0.55% per person-year, which rose to 0.96% per person-year following HBeAg-seroconversion.
The researchers also reported a significantly greater prevalence of HBsAg titers less than 1,000 IU/mL and of HBV DNA less than 10,000 IU/mL at 18 months following seroconversion among those who achieved functional vs. nonfunctional cure.
Multivariate Cox proportional hazard analysis showed predictors of functional cure included HBeAg-seroconversion at aged younger than 18 years (P < .001), high genetic barrier nucleos(t)ide analogue(s) therapy prior to seroconversion (P = .001) and a serum HBsAg titer less than 1,000 IU/mL at 18 months after seroconversion (P = .001). The researchers confirmed these results via univariate Cox proportional hazard analysis (HRs = 3.5, 2.07 and 3.09, respectively).
“Our study is the first to report on the cumulative probability and predictors of functional cure in chronic HBV-infected patients who were followed from childhood into adulthood,” Wu and colleagues wrote. “HBeAg-seroconversion in childhood, high genetic barrier nucleos(t)ide analogue(s) therapy in young patients before HBeAg-seroconversion and low HBsAg titers after HBeAg-seroconversion are linked to a functional cure for chronic HBV infection.”
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