恩替卡韦治疗后慢性乙型肝炎低病毒血症患者序贯联合艾米替诺福韦治疗的效果研究

Clinical efficacy of sequential tenofovir amibufenamide therapy in chronic hepatitis B patients with low-level viremia after entecavir treatment

摘要:

目的 探讨在恩替卡韦（ETV）治疗后出现低病毒血症（LLV）的慢性乙型肝炎（CHB）患者，采取序贯联合艾米替诺福韦（TMF）治疗的临床效果。方法 选取2021年7月—2023年1月在贵港市人民医院感染科经ETV抗病毒治疗的CHB患者200例。根据治疗期间HBV DNA水平，将患者分为完全病毒学应答组（64例）和LLV组（136例），分析两组临床资料。根据LLV组抗病毒治疗方案，分为3组：续用ETV为对照组（40例）、换用TMF为序贯组（45例）、ETV联合TMF为联合组（51例），持续治疗48周。比较3组治疗48周时HBV DNA转阴率、乙肝表面抗原（HBsAg）、E抗原（HBeAg）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肌酐（Cr）和肝硬度测定值（LSM）及不良反应发生率。结果 完全病毒学应答组HBeAg阳性率、HBV DNA、PLT、LSM、ALT、AST均低于LLV组（P <0.05）。治疗24周后，完全病毒学应答组Cr、AST、HBeAg阳性率、HBV DNA、PLT均低于LLV组（P <0.05）。治疗48周后，联合组Cr低于对照组和序贯组（P <0.05），HBsAg高于对照组和序贯组（P <0.05）；序贯组ALT、AST均低于对照组（P <0.05）；序贯组和联合组HBeAg转阴率、HBV DNA转阴率、PLT均高于对照组（P <0.05），LSM低于对照组（P <0.05）。对照组、序贯组、联合组不良反应总发生率比较，差异无统计学意义（P >0.05）。结论 序贯或联合TMF治疗能更有效地提高ETV治疗后LLV患者完全病毒学应答率，并改善患者肝肾功能，减轻肝纤维化程度。

Abstract:

Objective To explore the clinical efficacy of sequential tenofovir amibufenamide (TMF) therapy in chronic hepatitis B (CHB) patients with low-level viremia (LLV) after treatment with entecavir (ETV).Methods A total of 200 CHB patients undergoing antiviral therapy with ETV in the Department of Infectious Diseases of Guigang People's Hospital from July 2021 to January 2023 were selected. According to the HBV DNA levels during treatment, patients were divided into a complete virological response group (64 cases) and an LLV group (136 cases), and the clinical data of both groups were analyzed. Based on the antiviral treatment regimen of patients in the LLV group, they were subdivided into the control group (40 cases treated with ETV), the sequential group (45 cases treated with TMF), and the combination group (51 cases treated with ETV and TMF). All patients received continuous treatment for 48 weeks. The negative conversion rate of HBV DNA, positivity of hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr), liver stiffness measurement (LSM) and the incidence of adverse reactions were compared among the three groups at 48 weeks.Results The positivity rate of HBeAg, the levels of HBV DNA, PLT, ALT and AST, and LSM in the complete virological response group were lower than those in the LLV group (P < 0.05). After 24 weeks of treatment, the levels of Cr, AST, HBV DNA and PLT, and the positivity rate of HBeAg in the complete virological response group were lower than those in the LLV group (P < 0.05). After 48 weeks of treatment, the level of Cr was lower and the level of HbsAg was higher in the combination group than in the control group and the sequential group (P < 0.05). The levels of ALT and AST in the sequential group were lower than those in the control group (P < 0.05). The negative conversion rates of HBeAg and HBV DNA and the level of PLT in the sequential group and the combination group were higher than those in the control group (P < 0.05), while the LSM in the sequential group and the combination group was lower than that in the control group (P < 0.05). There was no statistically significant difference in the overall incidence of adverse reactions among the three groups (P > 0.05).Conclusions Sequential or combined TMF therapy more effectively increases the complete virological response rate in patients with LLV after ETV treatment. Besides, it improves the liver and kidney function and reduces the degree of liver fibrosis in these patients.