Objective: This study utilized real-world medical insurance settlement data to conduct a comparative evaluation of the clinical efficacy of Entecavir (ETV) generic drugs and the original drugs in delaying disease progression in chronic hepatitis B (CHB). Methods: The study employed relational graph convolutional networks (RGCN) and heterogeneous graph attention (HGT) networks to standardize the identification of clinical behaviors and drug specifications, while employing the Kalman filtering algorithm to quantify patient prescription adherence. Propensity score matching (PSM) was used to balance baseline characteristics, and Cox proportional hazards regression models were applied to compare the risk differences between the two groups for severe liver events such as hepatocellular carcinoma (HCC), liver failure, and hepatic ascites. Results: After algorithmic bias control and correction, a total of 1481 patients were included (987 in the generic drug group and 494 in the original drug group). The Log-rank test revealed no statistically significant differences between the two groups in the incidence of HCC (P=0.097), liver failure (P=0.165), or hepatic ascites (P=0.661). Cox regression analysis demonstrated that the hazard ratio (HR) for HCC in the generic drug group was 1.21 (95% CI: 0.47-3.14), for liver failure HR was 0.58 (95% CI: 0.25-1.33), and for hepatic ascites HR was 1.13 (95% CI: 0.73-1.75), with all 95% CIs containing 1.0. Conclusion: After rigorous cleaning to exclude non-standard drug use and compliance-related confounders, there is no evidence of significant differences between ETV generic drugs and the original drugs in controlling hepatic hard-endpoint events, yielding robust and reliable conclusions. The findings provide real-world evidence of therapeutic equivalence to support the centralized drug procurement policy, as well as a reliable case study in the field of real-world research for coordinated development and regulation of medical insurance, medical services, and pharmaceuticals.
Key words
Entecavir /
generic drug /
consistency evaluation /
original drug /
clinical efficacy comparison /
real-world study
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References
[1] 国家药品监督管理局药品审评中心.恩替卡韦分散片说明书[EB/OL].[2026-04-12].https://www.cde.org.cn/hymlj/download/sms/8e1e0c145a80fb55009bdf86ce93a508.
[2] 中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2022年版)[J].实用肝脏病杂志,2023,26(3):18-39.
[3] 殷瑞,马国伟,岳雯溪,等.核苷酸类似物单药与联合干扰素治疗慢性乙肝的疗效[J].昆明医科大学学报,2025,46(6):79-88.
[4] 唐淬蓉,胡承光,周宇辰,等.乙型肝炎肝硬化合并糖尿病时发生肝细胞癌的风险:一项随访5年的前瞻性队列研究[J].南方医科大学学报,2021,41(3):313-318.
[5] LUBEL J S, STRASSER S I, THOMPSON A J, et al.Australian consensus recommendations for the management of hepatitis B[J]. Medical journal of Australia, 2022, 216(6): 309-318.
[6] ROGAL S S, HANSEN L, PATEL A, et al.AASLD practice guidance: palliative care and symptom-based management in decompensated cirrhosis[J]. Hepatology, 2022, 76(3): 819-853.
[7] European Association For the Study of the Liver. EASL clinical practice guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis[J]. Journal of hepatology, 2022, 76(5):1151-1184.
[8] European Association For the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma[J].Journal of hepatology,2018,69(1):182-236.
[9] WEISSENBORN K.Hepatic encephalopathy: definition, clinical grading and diagnostic principles[J]. Journal of clinical and experimental hepatology,2019,9(6): 719-726.
[10] TUJIOS S, STRAVITZ R T, LEE W M.Management of acute liver failure: update 2022[J]. Seminars in liver disease,2022,42(3):362-378.
[11] GINÈS P, CÁRDENAS A, ARROYO V, et al. Management of cirrhosis and ascites[J]. New England journal of medicine, 2004, 350(16): 1646-1654.
[12] GISH R G, LOK A S F, CHANG T T, et al. Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B[J].Gastroenterology, 2007, 133(5):1437-1444.
[13] AHN Y E, KIM S E, CHON H R, et al.Maintaining antiviral efficacy after switching to generic entecavir 1 mg[J]. Korean journal of gastroenterology, 2021, 77(1): 22-29.
[14] KIM D Y, HEO N Y, LEE H C, et al.Baracle® vs Baraclude® for 48 weeks: a prospective, multicenter, randomized, open-label, parallel-group study[J]. Drug design, development and therapy,2017(11):3145-3152.
