Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study

• Published in: Clinical gastroenterology and hepatology Vol. 23; no. 4; pp. 583 - 590.e3
• Main Authors: Wu, Jia-Feng, Tai, Chi-San, Chang, Kai-Chi, Chen, Yuh-Jue, Hsu, Chien-Ting, Chen, Huey-Ling, Ni, Yen-Hsuan, Chang, Mei-Hwei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2025
• Subjects: Adolescent; Adult; Antiviral Agents - therapeutic use; DNA, Viral - blood; Female; Follow-Up Studies; Functional Cure; Gastroenterology and Hepatology; Hepatitis B e Antigen Seroconversion; Hepatitis B e Antigens - blood; Hepatitis B Surface Antigen; Hepatitis B Surface Antigens - blood; Hepatitis B, Chronic - drug therapy; Humans; Male; Middle Aged; Retrospective Studies; Seroconversion; Treatment Outcome; Young Adult; Hepatitis B e Antigen Seroconversion; CI; HBeAg; ALT; HBsAg; HCC; HR; anti-HBe; NHI; NA; EASL; Functional Cure; LLOD; AASLD; HBV; Hepatitis B Surface Antigen; hepatitis B virus; alanine aminotransferase; hepatitis B e antigen; hepatitis B e antibody; hepatocellular carcinoma; nucleos(t)ide analogue; European Association for the Study of the Liver; American Association for the Study of Liver Diseases; lower limit of detection; hazard ratio; confidence interval; National Health Insurance
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2024.07.036

A functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg) seroconversion. We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV–infected patients who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per person-year, and increased to 0.96% per person-year after HBeAg seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazards analysis of the cohort revealed that HBeAg seroconversion at <18 years of age, high-genetic-barrier nucleos(t)ide analogue(s) therapy before HBeAg seroconversion, and a serum HBsAg titer <1000 IU/mL at 18 months after HBeAg seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). In a cohort of chronic HBV–infected patients with long-term follow-up, HBeAg seroconversion in childhood, high-genetic-barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg seroconversion were significant predictors of functional cure.