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老年低蛋白血症患者发生伏立康唑相关肝损伤的独立危险因素

          分析
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          周丽娟 ,何 勐 ,张 玮 ,王 娜 ,李慧红 ,申明慧 ,靳巍巍(1.郑州大学附属郑州中心医院药学部,郑州
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          450007;2.郑州大学附属郑州中心医院综合办公室,郑州 450007)
          中图分类号  R969.3;R978.5      文献标志码  A      文章编号  1001-0408(2024)24-3035-06
          DOI  10.6039/j.issn.1001-0408.2024.24.12
          摘  要  目的  探讨老年低蛋白血症患者发生伏立康唑(VCZ)相关肝损伤的独立危险因素。方法  选取2020年8月-2023年7月
          我院呼吸重症监护室使用VCZ治疗的侵袭性真菌感染的老年低蛋白血症患者,按用药后是否发生肝损伤分为A组(发生肝损伤)
          和B组(未发生肝损伤)。采用Pearson相关分析法分析VCZ谷浓度(cmin )与炎症因子[C反应蛋白(CRP)、降钙素原(PCT)、白细胞
          介素 6(IL-6)]、肝功能指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素
         (TBIL)]的相关性;采用χ 检验进行单因素分析;采用Logistic回归分析影响肝损伤发生的独立危险因素。结果  纳入320例患者,
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          有 56 例患者发生了肝损伤,肝损伤发生率为 17.50%。A 组患者的 VCZ cmin显著高于 B 组(P=0.021)。CRP、PCT、IL-6、TBIL 与
          VCZ cmin均存在相关性(P<0.05);CRP、PCT、IL-6、TBIL对VCZ cmin有显著影响(P<0.05);VCZ cmin、PCT、TBIL是影响肝损伤发生
          的独立危险因素(P<0.05);VCZ cmin≥3.76 mg/L的患者肝损伤风险显著增加。结论  VCZ cmin、PCT、TBIL是影响老年低蛋白血症
          患者发生VCZ相关肝损伤的独立危险因素;对于PCT或TBIL高的患者,使用VCZ期间,应密切监测VCZ cmin和肝功能,以降低肝
          损伤的发生风险。
          关键词  伏立康唑;肝损伤;老年;低蛋白血症;谷浓度;炎症因子;独立危险因素

          Analysis  of  independent  risk  factors  for  voriconazole-related  liver  injury  in  elderly  patients  with
          hypoproteinemia
          ZHOU Lijuan ,HE Meng ,ZHANG Wei ,WANG Na ,LI Huihong ,SHEN Minghui ,JIN Weiwei(1.  Dept.  of
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          Pharmacy, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China; 2. General
          Office, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China)
          ABSTRACT   OBJECTIVE To explore the independent risk factors of voriconazole (VCZ)-related liver injury in elderly patients
          with  hypoproteinemia.  METHODS  Elderly  patients  with  invasive  fungal  infection  and  hypoproteinemia  who  were  hospitalized  in
          the  respiratory  intensive  care  unit  of  our  hospital  and  treated  with  VCZ  from August  2020  to  July  2023  were  selected.  They  were
          divided  into  group A (liver  injury  group)  and  group  B (non-liver  injury  group)  based  on  whether  the  liver  injury  occurred  after
          using  VCZ.  Pearson  correlation  analysis  was  used  to  analyze  the  correlation  between  minimum  concentration (cmin )  of  VCZ  and
          inflammatory  factor[C-reactive  protein (CRP),  procalcitonin (PCT),  interleukin-6 (IL-6)],  as  well  as  liver  function  [alanine
          transaminase (ALT),  aspartate  transaminase (AST),  alkaline  phosphatase (ALP),  gamma-glutamyl  transpeptidase (GGT),  total
          bilirubin (TBIL)];  univariate  analysis  was  performed  by  using  χ   test;  Logistic  regression  analysis  was  used  to  analyze  the
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          independent  risk  factors  affecting  the  occurrence  of  liver  injury.  RESULTS  A  total  of  320  patients  were  included  in  the  study,  of
          whom 56 developed liver injury, with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B (P=
          0.021).  CRP,  PCT,  IL-6,  and  TBIL  were  correlated  with  VCZ  cmin (P<0.05).  CRP,  PCT,  IL-6,  and  TBIL  had  a  significant
          impact  on  VCZ  cmin (P<0.05).  VCZ  cmin,  PCT,  and  TBIL  were  independent  risk  factors  for  liver  injury (P<0.05).  The  patients
          with  VCZ  cmin≥3.76  mg/L  had  a  significantly  increased  risk  of  liver  injury.  CONCLUSIONS  VCZ  cmin,  PCT,  and  TBIL  are
          independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and
          TBIL, VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.
          KEYWORDS    voriconazole;  liver  injury;  elderly;  hypoproteinemia;  minimum  concentration;  inflammatory  factor;  independent
          risk factor


                                                                 侵袭性真菌感染是一种由真菌侵入体内,并在组
             Δ 基金项目 河南省科技发展计划项目(No.222102310224);河南          织、器官或血液中生长繁殖而引起的一种感染性疾病,
          省医学科技攻关计划项目(No.LHGJ20191056,No.LHGJ20230777);
                                                             其在免疫力低下人群中的发病率和致死率均较高,主要
          河南省高等学校重点科研项目(No.21B360010)
                                                                              [1]
                                                             病因为曲霉菌感染 。伏立康唑(voriconazole,VCZ)是
             *第一作者 主任药师,硕士。研究方向:药物分析学和药物基因
          组学。E-mail:zhou750423@126.com                       一种具有广谱活性的第二代三唑类抗真菌药,已被《伏

          中国药房  2024年第35卷第24期                                              China Pharmacy  2024 Vol. 35  No. 24    · 3035 ·
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