Background:Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss,termed functional cure, based on previous published studies.However,it is not known which strategy is more cost-effective on functional cure.The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.Methods:A Markov model was developed with functional cure and other five states including CHB,compensated cirrhosis,decompensated cirrhosis,hepatocellular carcinoma,and death to assess the cost-effectiveness of seven representative treatment strategies.Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators,respectively.Results:In the two base-case analysis,compared with ETV,ETV generated the highest costs with $44,210 and the highest qualityadjusted life-years (QALYs) with 16.78 years.Compared with TDF,treating CHB patients with ETV and NA-PegIFN strategies increased costs by $7639 and $6129,respectively,gaining incremental QALYs by 2.20 years and 1.66 years,respectively.The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY,respectively,which were less than one-time gross domestic product per capita.One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.Contusion:Among seven treatment strategies,first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.