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富马酸丙酚替诺福韦对恩替卡韦经治后低病毒载量的慢性乙型肝炎患者的临床疗效
DOI: 10.3969/j.issn.1001-5256.2022.03.009
伦理学声明：本研究方案于2021年7月19日经由武汉市金银潭医院伦理委员会审批，批号：KY-2021-07，所纳入患者均签署知情同意书。
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：程海林、胡旭东责研究设计，资料分析及论文撰写；夏冰、柏涛负责数据收集及统计分析；卢斯霞负责患者随访。
Clinical effect of tenofovir alafenamide fumarate on chronic hepatitis B patients with low viral load after entecavir treatment
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摘要:
目的 观察富马酸丙酚替诺福韦(TAF)对恩替卡韦(ETV)治疗后低病毒血症的慢性乙型肝炎患者的疗效。 方法 选取2019年3月—2020年10月在武汉市金银潭医院经ETV抗病毒治疗的慢性乙型肝炎患者160例，经倾向评分匹配分为试验组和对照组各80例。试验组换用TAF抗病毒治疗，对照组继续ETV治疗，持续治疗24周。观察2组患者治疗后HBV DNA阴转率、HBeAg阴转率、ALT水平、肾小球滤过率(eGFR)、FIB-4值、肝硬度值变化及药物不良反应发生情况。计量资料2组间比较采用t检验，计数资料2组间比较采用χ2检验。 结果 治疗24周后，试验组HBV DNA阴转率较对照组明显升高(96.25%vs 16.25%，χ2=104.03，P＜0.001), HBeAg阴转率较对照组明显升高(34.78%vs 11.90%，χ2=6.32，P＜0.05)。试验组ALT、eGFR、FIB-4值及肝硬度值与对照组比较均有不同程度改善(t值分别为5.77、4.21、8.45、4.58，P值均＜0.05)，用药期间对照组及试验组的药物不良反应发生率分别为7.50%和8.75%，2组间差异无统计学意义(P＞0.05)。 结论 对ETV经治后低病毒血症的慢性乙型肝炎患者，更换TAF抗病毒治疗能够有效提高低病毒血症患者的HBV DNA及HBeAg阴转率，并且能够明显改善患者肝肾功能、减轻肝纤维化程度，治疗安全性好。 Abstract:Objective To investigate the clinical effect of tenofovir alafenamide fumarate (TAF) on chronic hepatitis B (CHB) patients with low-level viremia (LLV) after entecavir (ETV) treatment. Methods A total of 160 CHB patients who received ETV antiviral therapy in Wuhan Jinyintan Hospital from March 2019 to October 2020 were enrolled and divided into experimental group and control group by propensity score matching, with 80 patients in each group. The patients in the experimental group were given TAF antiviral therapy, and those in the control group were given ETV treatment; the course of treatment was 24 weeks for both groups. The two groups were compared in terms of HBV-DNA clearance rate, HBeAg clearance rate, alanine aminotransferase (ALT) level, estimated glomerular filtration rate (eGFR), FIB-4 value, liver stiffness measurement, and adverse drug reactions after treatment. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Results After 24 weeks of treatment, compared with the control group, the experimental group had significantly higher HBV DNA clearance rate (96.25% vs 16.25%, χ2 =104.03, P < 0.001) and HBeAg clearance rate (34.78% vs 11.90%, χ2=6.32, P < 0.05). Compared with the control group, the experimental group had varying degrees of improvement in ALT, eGFR, FIB-4, and liver stiffness measurement (t=5.77, 4.21, 8.45, and 4.58, all P < 0.05), and there was no significant difference in the incidence rate of adverse drug reactions between the control group and the experimental group during treatment (7.50% vs 8.75%, P > 0.05). Conclusion For CHB patients with LLV after ETV treatment, the change to TAF antiviral therapy can effectively increase their HBV DNA clearance rate and HBeAg clearance rate, improve liver and renal function, and reduce the degree of liver fibrosis, with good safety. -
Key words:
- Hepatitis B, Chronic /
- Low-Level Viremia /
- Entecavir /
- Propofol Tenofavir Fumarate
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表 1 2组患者治疗前一般资料比较
指标 对照组(n=80) 试验组(n=80) 统计值 P值 男/女(例) 48/32 47/33 χ2=0.02 0.991 年龄(岁) 35.82±8.26 35.57±8.49 t=0.21 0.837 BMI (kg/m2) 21.88±1.92 22.03±1.97 t=0.49 0.676 病程(年) 3.17±1.23 3.21±1.37 t=0.19 0.852 ALT(U/L) 34.8±18.2 35.2±17.6 t=0.14 0.867 HBeAg阳性率[例(%)] 42(52.5) 46(53.8) χ2=0.40 0.781 HBV DNA(log IU/mL) 2.13±0.44 2.15±0.52 t=0.26 0.765 eGFR(mL·min-1·1.73 m-2) 97.85±16.22 98.06±17.11 t=0.08 0.901 FIB-4 2.23±0.62 2.26±0.71 t=0.28 0.728 肝硬度值(kPa) 7.36±3.32 7.41±3.64 t=0.09 0.893 
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表 2 2组患者治疗后HBeAg和HBV DNA转阴率比较
指标 对照组 试验组 χ2值 P值 HBV DNA阴转率(%) 16.25(13/80) 96.25(77/80) 104.03 ＜0.001 HBeAg阴转率(%) 11.90(5/42) 34.78(16/46) 6.32 0.028
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表 3 2组治疗后ALT、eGFR、FIB-4和肝硬度值比较
指标 对照组(n=80) 试验组(n=80) t值 P值 ALT(U/L) 37.2±21.7 21.3±11.7 5.77 ＜0.001 eGFR(mL·min-1·1.73 m-2) 95.36±14.74 107.23±20.46 4.21 0.002 FIB-4 2.55±0.76 1.68±0.52 8.45 ＜0.001 肝硬度值(kPa) 8.48±3.73 6.13±2.68 4.58 0.001
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