Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B
Yao‐Chun Hsu, Ming‐Lun Yeh, Grace Lai‐Hung Wong, Chien‐Hung Chen, Cheng‐Yuan Peng, Marı́a Buti, Masaru Enomoto, Qing Xie, Huy N. Trinh, Carmen Monica Preda, Li Liu, Ka Shing Cheung, Yee Hui Yeo, Joseph Hoang, Chung‐Feng Huang, Mar Riveiro‐Barciela, Ritsuzo Kozuka, Doina Istrătescu, Pei‐Chien Tsai, Elena Vargas Accarino, Dong-Hyun Lee, Jia‐Ling Wu, Jee Fu Huang, Chia‐Yen Dai, Ramsey Cheung, Wan‐Long Chuang, Man‐Fung Yuen, Vincent Wai‐Sun Wong, Ming‐Lung Yu, Mindie H. Nguyen
Abstract
BACKGROUND: Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. METHODS: This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. RESULTS: The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]). CONCLUSION: HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.