Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B

• Published in: The Journal of infectious diseases Vol. 224; no. 11; pp. 1890 - 1899
• Main Authors: Hsu, Yao-Chun, Yeh, Ming-Lun, Wong, Grace Lai-Hung, Chen, Chien-Hung, Peng, Cheng-Yuan, Buti, Maria, Enomoto, Masaru, Xie, Qing, Trinh, Huy, Preda, Carmen, Liu, Li, Cheung, Ka-Shing, Yeo, Yee Hui, Hoang, Joseph, Huang, Chung-Feng, Riveiro-Barciela, Mar, Kozuka, Ritsuzo, Istratescu, Doina, Tsai, Pei-Chien, Accarino, Elena Vargas, Lee, Dong-Hyun, Wu, Jia-Ling, Huang, Jee Fu, Dai, Chia-Yen, Cheung, Ramsey, Chuang, Wan-Long, Yuen, Man-Fung, Wong, Vincent Wai-Sun, Yu, Ming-Lung, Nguyen, Mindie H
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.12.2021
• Subjects: Alanine; Alanine transaminase; Alanine Transaminase - blood; Antiretroviral drugs; Antiviral Agents - therapeutic use; Antiviral drugs; Bilirubin; Bilirubin - blood; China - epidemiology; Cohort Studies; Confidence intervals; DNA viruses; DNA, Viral; Fatty Liver; Female; Guanine - analogs & derivatives; Guanine - therapeutic use; Hepatitis; Hepatitis B; Hepatitis B surface antigen; Hepatitis B Surface Antigens - blood; Hepatitis B virus - genetics; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - epidemiology; Humans; Incidence; Interferon; Male; Middle Aged; Patients; Tenofovir; Tenofovir - therapeutic use; Treatment Outcome; Viremia; China; hepatitis B surface antigens; entecavir; functional cure; REAL-B; tenofovir; hepatitis B virus
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiab241

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.