Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens
FUNDING INFORMATION
This study was funded by the Beijing Municipal Science & Technology Commission (grant no. Z151100004015122), Beijing Hospitals Authority Clinical medicine Development of special funding support (grant no. XMLX 201706 and XMLX 202127), National Science and Technology Major Project of China (grant no. 2017ZX10201201-001-006, 2017ZX10201201-002-006, and 2018ZX10715-005-003-005), Beijing Science and Technology Commission Research Project (grant no. D161100002716002), and the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (grant no. XXZ0302 and XXT28).
Abstract
Background & Aims
Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse.
Methods
Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse.
Results
420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group.
Conclusion
NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).
CONFLICT OF INTEREST
Dr. Calvin Q. Pan is a consultant for Gilead. He also received a research grant from Gilead. Drs. Ming-Hui Li, Wei Yi, Lu Zhang, Yao Lu, Hong-Xiao Hao, Gang Wan, Wei-Hua Cao, Xing-Yue Wang, Chong-Ping Ran, Ge Shen, Shu-Ling Wu, Min Chang, Yuan-Jiao Gao and Yao Xie have no financial interests to disclose.
Writing assistance
This manuscript is prepared by its authors without outside assistance.
