Objectives: Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF.
Methods: The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．.
Results: After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group.
Conclusions: TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.
目的: 乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure，HBV-ACLF)是我国最常见的肝衰竭类型，病死率很高。早期快速降低HBV-DNA载量可提高HBV-ACLF患者的存活率，目前常用的药物有核苷(酸)类似物，如恩替卡韦(entecavir，ETV)、替诺福韦等。新上市的富马酸丙酚替诺福韦(tenofovir alafenamide fumarate，TAF)以其更强效的抗病毒作用、更高的转氨酶复常率、更好的骨肾安全性及零耐药等优点，得到临床医师的极大关注。但关于TAF治疗中国HBV-ACLF患者的疗效及安全性的临床研究数据较少，且缺乏药物经济学评价。本研究旨在比较TAF与ETV治疗HBV-ACLF的疗效、安全性和经济学成本。方法: 回顾性分析2020年5月至2021年3月于中南大学湘雅医院住院的HBV-ACLF患者196例，其中前期66例、早期57例、中期43例和晚期30例。根据用药情况分为TAF组80例，ETV组116例。比较2组患者治疗前、治疗2、4周的生化及病毒学指标；治疗12周，比较2组患者的肝移植率+病死率、并发症发生率等。采用最小成本分析法比较2种药物的成本-效果比值，进行药物经济学评价。结果: 治疗4周时，2组疗效(肝功能、病毒载量)差异均无统计学意义(均P>0.05)；与ETV组相比，TAF组的血肌酐水平更低[(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L，P<0.05]，估计肾小球滤过率水平更高[(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2)，P<0.05]。治疗12周时，2组的总体肝移植率+病死率差异无统计学意义(P>0.05)，TAF组肝衰竭前期患者的肝移植率+病死率低于ETV组(0 vs 13.89%，P<0.05)。在肝衰竭早期、中期、晚期，2组的肝移植率+病死率差异均无统计学意义(13.04% vs 17.65%、37.50% vs 37.04%、54.55% vs 68.42%，均P>0.05)。在12周的观察期内，2组均未观察到药物相关不良事件发生。TAF组的成本-效果比值较低，治疗成本较低。结论: TAF与ETV在改善HBV-ACLF患者肝功能及降低病毒载量方面无明显差异；二者的安全性相当。TAF对肾功能的保护更具优势，可降低肝衰竭前期患者的肝移植率+病死率；TAF在药物经济学评价方面优于ETV。.
Keywords: cost-effectiveness; efficacy; entecavir; hepatitis B virus-related acute-on-chronic liver failure; safety; tenofovir alafenamide fumarate.