丙酚替诺福韦治疗失代偿期乙型肝炎肝硬化应答不佳/低病毒血症的疗效及安全性

Efficacy and safety of switching to tenofovir alafenamide in poor responsive/low-level viremia hepatitis B patients with decompensated cirrhosis to nucleos(t)ide analogs therapy

目的评估丙酚替诺福韦(tenofovir alafenamide,TAF)单药治疗失代偿期乙型肝炎肝硬化应答不佳/低病毒血症(LLV)患者的效果和安全性。方法纳入经治应答不佳/LLV失代偿期乙型肝炎肝硬化患者56例,转换为TAF单药治疗,每12周进行1次随访。根据基线HBV DNA水平,分为LLV组(HBV DNA<2000 IU/mL)和应答不佳组(HBV DNA≥2000 IU/mL),比较两组的病毒学应答率。统计分析疗效及安全性。结果转换为TAF治疗48周的完全病毒学应答率显著高于12周,分别为80.00%(16/20)和32.14%(18/56)(P<0.05)。LLV组和应答不佳组12周的完全病毒学应答率分别为61.54%(16/26)和6.67%(2/30),差异有统计学意义(P<0.05),而24周、36周及48周的完全病毒学应答率差异无统计学意义(P>0.05)。48周的血清HBsAg定量和HBV DNA水平较基线分别下降0.44和3.38 lgIU/mL,差异有统计学意义(P<0.05)。48周时ALT复常率为95.00%(19/20),高于基线水平的66.07%(37/56)(P<0.05)。治疗48周时Child-pugh评分为5.45±0.76,低于基线的8.66±2.30;而48周时Child A级比例较基线显著增高,分别为85%(17/20)和21.43%(12/56)(P<0.05)。在48周治疗期间,肌酐、eGFR均无明显变化,尿β2微球蛋白较基线下降,中位数分别为1.14和0.98(P>0.05)。结论经核苷(酸)类似物抗病毒治疗的失代偿期乙型肝炎肝硬化患者因应答不佳/LLV转换为TAF单药治疗后,病毒学抑制率及ALT复常率显著提高,肝功能得到改善,安全性良好。

Objective Real-world efficacy and safety of switching to TAF in decompensated hepatitis B-related cirrhotic patients poor responsive or with low-level viremia(LLV)to nucleos(t)ide analogue(NA)therapy are unclear.The purpose of this study was to investigate the efficacy and safety of the sequential therapy in order to optimize antiviral treatment.Methods In this prospective cohort study 56 patients with decompensated hepatitis B cirrhosis were enrolled who had been switched to TAF monotherapy due to poor response to NA therapy or LLV for at least 6 mooths.According to the baseline HBV DNA level,they were divided into LLV group(HBVDNA<2000 IU/mL)and poor response group(HBV-DNA≥2000 IU/mL).All patients were followed up every 12 weeks.Their virological/biochemical responses were evaluated after switchover.Results(1)Complete virological response(CVR)at 48 weeks[32.14%(18/56)]after swithing to TAF was significantly increased than that at 12 weeks[80.00%(16/20)](P<0.05).(2)Subgroup analysis of LLV group and poor response group showed that the former achieved favours CVR at 12 weeks[61.54%(16/26)vs 6.67%(2/30)].However,there was no statistical difference between the two groups at 24 weeks,36 weeks and 48 weeks.(3)Additionally,the mean changes in HBsAg and HBV DNA levels were significant at 48 weeks(-0.44 and-3.38 logIU/mL,respectively)(P<0.05).(4)The normalization rate of ALT at 48 week was 95.00%(19/20),which were significantly higher than that of 66.07%(37/56)at the baseline(P<0.05).(5)The mean Child-Pugh score and the proportion of Child-pugh A at 48 weeks was 5.45±0.76 and 85%(17/20),respectively,which were significantly improved than those of 8.66±2.30 and 21.43%(12/56)at the baseline(P<0.05).(6)During the 48-weeks’treatment period,there were no significant changes in serum creatinine,phosphorus,and eGFR(P>0.05),However,the median urinaryβ2-microglobulin(β2-MG)at 24-weeks was 0.98,compared to 1.14 at the baseline,however,the difference was not statistically significant.Conclusion(1)Switching to TAF monotherapy is effective in patients with decompensated hepatitis B-related cirrhosis due to poor response to NA therapy/LLV,regarding both CVR and the liver function benefits.(2)TAF has a good renal safety in the treatment of decompensated hepatitis B-related cirrhosis.