恩替卡韦和富马酸丙酚替诺福韦治疗高病毒载量慢性乙型肝炎的疗效和安全性比较

摘要/Abstract

摘要： 目的对比高病毒载量慢性乙型肝炎(CHB)患者采用富马酸丙酚替诺福韦与恩替卡韦的效果。方法选取上海交通大学医学院附属仁济医院宝山分院2021年5月—2023年10月收诊的高病毒载量CHB患者104例。以随机数字表法将其分成观察组与对照组,分别采用富马酸丙酚替诺福韦、恩替卡韦治疗,各52例。对比两组肝功能、肠道屏障功能、疗效、安全性及炎症反应。结果观察组的HBV DNA转阴率、丙氨酸氨基转移酶(ALT)复常率、HBeAg转阴率分别为94.23%、94.23%、11.54%,对照组分别为84.62%、90.38%、7.69%,两组对比结果显示并无显著差异(P>0.05)。治疗后,观察组的血清降钙素原(PCT)、天冬氨酸氨基转移酶(AST)、肿瘤坏死因子α(TNF-α)、HBV DNA、ALT、白细胞介素-4(IL-4)分别为(0.03±0.01)μg/L、(36.16±4.42)U/L、(11.24±2.71)ng/L、(1.62±0.36)lgIU/mL、(37.43±4.94)U/L、(47.16±4.61)ng/L,对照组分别为(0.03±0.01)μg/L、(37.51±4.78)U/L、(11.54±2.95)ng/L、(1.74±0.35)lgIU/mL、(38.81±5.39)U/L、(47.94±4.82)ng/L,两组比较差异无统计学意义(P>0.05)。治疗后,两组血清内霉素、二胺氧化酶、D-乳酸水平比较无显著差异(P>0.05)。治疗后,观察组的低密度脂蛋白胆固醇为(2.31±0.43)mmol/L、高密度脂蛋白胆固醇(1.32±0.34)mmol/L,低于对照组[分别为(2.70±0.52)mmol/L、(1.65±0.52)mmol/L](P<0.05),两组血肌酐、估算的肾小球滤过率(eGFR)比较无显著差异(P>0.05)。结论高病毒载量CHB患者无论采用恩替卡韦还是富马酸丙酚替诺福韦均可获得满意效果,二者均可减轻炎症反应,改善肝功能与肠道屏障功能,对肾功能均无明显影响,但服用恩替卡韦会影响患者血脂水平。

关键词: 恩替卡韦, 富马酸丙酚替诺福韦, 高病毒载量, 慢性乙型肝炎, 疗效, 安全性

Abstract: Objective To compare the efficacy of tenofovir fumarate and entecavir in patients with high viral load chronic hepatitis B (CHB).Methods A total of 104 CHB patients with high viral load were enrolled from Baoshan Branch of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2021 to October 2023. They were divided into observation group and control group by random number table method, with 52 cases each, and were treated with tenofovir pofol fumarate and entecavir respectively. Liver function, intestinal barrier function, efficacy, safety and inflammatory response were compared between the two groups.Results The HBV DNA negative conversion rate, alanine aminotransferase (ALT) normalization rate and HBeAg negative conversion rate were 94.23%, 94.23% and 11.54% in the observation group and 84.62%, 90.38% and 7.69% in the control group, respectively, and there were no difference between the two groups (P>0.05). After treatment, serum procalcitonin (PCT), aspartate aminotransferase (AST), tumor necrosis factor α (TNF-α), HBV DNA in the observation group, ALT, interleukin-4 (IL-4) were (0.03±0.01) μg/L, (36.16±4.42) U/L, (11.24±2.71) ng/L, (1.62±0.36) lgIU/mL, (37.43±4.94) U/L, (47.16±4.61), respectively. The corresponding values in control group was (0.03±0.01) μg/L, (37.51±4.78) U/L, (11.54±2.95) ng/L, (1.74±0.35) lgIU/mL, (38.81±5.39) U/L, (47.94±4.82) ng/L, respectively. There were no differences between the two groups (P>0.05). After treatment, there were no differences in serum endotoxin, diamine oxidase and D-lactic acid levels between the two groups (P>0.05). After treatment, the low-density lipoprotein cholesterol (LDL-C) (2.31±0.43) mmol/L and high-density lipoprotein cholesterol (HDL-C) (1.32±0.34) mmol/L in the observation group were lower than those in the control group [(2.70±0.52) mmol/L and (1.65±0.52) mmol/L, respectively] (P<0.05), there were no significant differences in serum creatinine and estimated glomerular filtration rate (eGFR) between the two groups (P>0.05).Conclusion Both entecavir and tenofovir fumarate can achieve satisfactory results in CHB patients with high viral load, both of which can reduce inflammation, improve liver function and intestinal barrier function, and have no significant effect on renal function. However, entecavir can affect blood lipid levels in patients.

Key words: Entecavir, Tenofovir pofol fumarate, High viral load, Chronic hepatitis B, Curative effect, Security

项伟艳, 朱扣云, 朱琦, 邱原元. 恩替卡韦和富马酸丙酚替诺福韦治疗高病毒载量慢性乙型肝炎的疗效和安全性比较[J]. 肝脏, 2025, 30(3): 371-375.

XIANG Wei-yan, ZHU Kou-yun, ZHU Qi, QIU Yuan-yuan. Comparison of efficacy and safety of Entecavir and Tenofovir profol fumarate in the treatment of chronic hepatitis B with high viral load[J]. Chinese Hepatolgy, 2025, 30(3): 371-375.

/ 推荐

参考文献

[1] 赖思敏, 赖小丽, 黄汐, 等. 核苷(酸)类似物经治序贯聚乙二醇干扰素治疗慢性乙型肝炎的荟萃分析[J]. 中国感染与化疗杂志,2019,19(5):489-494.
[2] Van Hees S, Cuypers B, Bourgeois S, et al. Sorted B cell transcriptomes point towards actively regulated B cell responses during ongoing chronic hepatitis B infections[J]. Cell Immunol, 2021,362(4):104283.
[3] Chan H, Buti M, Lim Y S, et al. Long-term treatment with tenofovir alafenamide for chronic hepatitis B results in high rates of viral suppression and favorable renal and bone safety[J]. Am J Gastroenterol, 2024,119(3):486-496.
[4] 彭湾, 曹红. 高病毒载量慢性乙型肝炎抗病毒治疗研究进展[J]. 新医学,2022,53(8):551-554.
[5] Choi W M, Kim G A, Choi J, et al. Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B[J]. J Clin Invest, 2022,132(10):e154833.
[6] Choi W M, Yip T C, Wong G L, et al. Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis[J]. J Hepatol, 2023,78(3):534-542.
[7] Aladag H, Aladag M. Is the use of Tenofovir Dipivoxil fumarate effective and safe in preventing vertical transmission in pregnant women with chronic HBV with high viral load?[J]. Eur Rev Med Pharmacol Sci, 2023,27(5):2091-2098.
[8] 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 中华肝脏病杂志,2019,27(12):938-961.
[9] Ji D, Chen Y, Bi J, et al. Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B[J]. J Hepatol, 2022,77(6):1515-1524.
[10] 周珲堃, 江建宁, 苏明华, 等. 恩替卡韦与替诺福韦酯治疗高病毒载量慢性乙型肝炎患者的效果分析[J]. 临床肝胆病杂志,2022,38(3):532-536.
[11] Yuan J, Peng Y, Hao F B, et al. No difference in hepatocellular carcinoma risk in chronic hepatitis B patients treated with tenofovir vs entecavir: evidence from an updated meta-analysis[J]. Aging (Albany NY), 2021,13(5):7147-7165.
[12] 李双玲, 刘丽, 陈艺, 等. 富马酸丙酚替诺福韦与恩替卡韦治疗高血清病毒载量的代偿期乙型肝炎肝硬化患者效果比较研究[J]. 实用肝脏病杂志,2024,27(5):749-752.
[13] Wu Z, Cao Y, Liu Z, et al. Study on the predictive value of laboratory inflammatory markers and blood count-derived inflammatory markers for disease severity and prognosis in COVID-19 patients: a study conducted at a university-affiliated infectious disease hospital[J]. Ann Med, 2024,56(1):2415401.
[14] Shabbir M, Badshah Y, Khan K, et al. Association of CTLA-4 and IL-4 polymorphisms in viral induced liver cancer[J]. BMC Cancer, 2022,22(1):518.
[15] Tiegs G, Horst A K. TNF in the liver: targeting a central player in inflammation[J]. Semin Immunopathol, 2022,44(4):445-459.
[16] 董建霞. 核苷(酸)类药物治疗慢性乙型病毒性肝炎的安全性及副作用分析[J]. 河南:郑州大学,2023.
[17] 娜丽, 萨仁娜, 赵海珍. 肠道菌群失衡与药物性肝损伤的相关性研究[J]. 中西医结合肝病杂志,2022,32(8):747-749.
[18] Huang Q, Li X M, Sun J P, et al. Tumor-derived endomucin promotes colorectal cancer proliferation and metastasis[J]. Cancer Med, 2023,12(3):3222-3236.
[19] Yang J, Gao H, Zhang T, et al. In vitro lactic acid bacteria anti-hepatitis B virus (HBV) effect and modulation of the intestinal microbiota in fecal cultures from HBV-associated hepatocellular carcinoma patients[J]. Nutrients, 2024,16(5):600.
[20] Li F C, Fan Y C, Li Y K, et al. Plasma diamine oxidase level predicts 6-month readmission for patients with hepatitis B virus-related decompensated cirrhosis[J]. Virol J, 2019,16(1):115.
[21] Pan S, Zhang Y, Zeng Y, et al. Comparison of the efficacy and safety of TAF, TDF, and LdT to prevent the transmission of hepatitis B in pregnant women: a retrospective study[J]. Immun Inflamm Dis, 2024,12(2):e1204.
[22] Lu Y X, He C Z, Wang Y X, et al. Effect of entecavir on the intestinal microflora in patients with chronic hepatitis B: a controlled cross-sectional and longitudinal real-world study[J]. Infect Dis Ther, 2021,10(1):241-252.
[23] Xu X, Jiang L, Zeng Y, et al. HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis[J]. Virol J, 2023,20(1):180.
[24] 常楚笛, 董晨, 赵素贤, 等. 慢性乙型肝炎一线抗病毒药物治疗效果及其安全性的真实世界研究[J]. 中华肝脏病杂志,2023,31(8):855-861.