张聪　　戴钱姣　　朱潇冉　　潘颖璐　　戴霞红

[關键词] 肝衰竭;侵袭性肺感染;伏立康唑;卡泊芬净;安全性

[中图分类号] R575.2          [文献标识码] B          [文章编号] 1673-9701（2021）14-0115-04

Comparison of efficacy of voriconazole and caspofungin in treatment of invasive lung infection complicated by liver failure

ZHANG Cong1   DAI Qianjiao2   ZHU Xiaoran1   PAN Yinglu1   DAI Xiahong3

1.Department of Pharmacy， Shulan（Hangzhou） Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College， Hangzhou   310000， China; 2.Department of Hepatobiliary Surgery，the First Affiliated Hospital of Zhejiang University Medical College， Hangzhou   310000， China; 3.Department of Infectious Disease， Shulan （Hangzhou） Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College， Hangzhou   310000， China

[Abstract] Objective To explore the efficacy of voriconazole and caspofungin in the treatment of invasive lung infection complicated by liver failure. Methods A total of 78 patients with ACLF complicated with IPA who were treated with voriconazole and caspofungin in our hospital from January 2016 to June 2020 were collected as the research subjects. A total of 29 patients treated with voriconazole were included in the voriconazole group， and 49 patients treated with caspofungin were included in the caspofungin group. The changes of liver function indexes and serum inflammatory factors， treatment effects， outcomes and adverse drug reactions were compared between the two groups before and after treatment. Results After treatment， the INR of the voriconazole group was （1.39±0.13）， which was lower than that of the caspofungin group （1.48±0.05）， and the difference between the two groups was statistically significant（P<0.05）. After treatment， the levels of white blood cell （WBC）， proealcitonin （PCT） and C-reactive protein （CRP） were （10.58±1.82） ×109/L， （1.49±0.41） ng/dL， and （34.88±6.44） mg/L in the voriconazole group， which were compared with （9.74±1.11）×109/L， （1.31±0.33） ng/dL， （35.33±6.37） mg/L in the caspofungin group， and no differences were statistically significant（P>0.05）. The improvement rate，and the survival rates after 4 weeks and 6 months follow-up were 89.66%， 68.97% and 58.62% respectively in the voriconazole group，and no statistical significances were observed when those were compared with 85.71%， 67.35% and 57.14% in the caspofungin group（P>0.05）. Conclusion Both voriconazole and caspofungin show good efficacy in the treatment of ACLF complicated with IPA， without obvious side effects.

[Key words] Liver failure; Invasive lung infection; Voriconazole; Caspofungin; Safety

肝衰竭为多种因素引起的严重肝功能损伤的终末期肝病，其中慢加急性肝衰竭（Acute-on-chronic liver failure，ACLF）是肝衰竭的主要类型[1]。30%～57%的ACLF由感染诱发，而并发感染的ACLF患者病死率是无感染并发症者的4倍，其中ACLF并发侵袭性肺部曲霉菌感染（Invasive pulmonary aspergillus，IPA）病死率超过70%[2]。对于IPA的治疗各国际学术组织先后出台了多项指南，明确推荐使用广谱抗真菌药物伏立康唑[3]。但近几年有研究报道指出其药动学呈现高度变异性，且存在一定的肝毒性，导致在肝衰竭这一特殊人群的治疗中使用受限[4]。卡泊芬净为棘白菌素类抗真菌药物，不属于CYP450酶抑制剂，对肝功能的影响小于伏立康唑，在肝衰竭患者早期抗曲霉菌治疗中是否存在优势需要进一步研究[5]。本研究比较伏立康唑与卡泊芬净治疗肝衰竭并发侵袭性肺感染的效果，现报道如下。

1 资料与方法

1.1 一般资料

收集2016年1月至2020年6月我院肝衰竭患者数据库中使用伏立康唑与卡泊芬净治疗的ACLF并发IPA患者78例。其中29例使用伏立康唑者纳入伏立康唑组，男25例，女4例，平均年龄（45.43±7.44）岁，肝衰竭原因：药物原因2例、PBC原因1例、单纯乙肝原因19例、单纯酒精原因2例、乙肝合并酒精5例;49例使用卡泊芬净者纳入卡泊芬净组，男40例，女9例，平均年龄（47.89±7.57）岁，肝衰竭原因：药物原因4例、PBC 1例、AIH 1例、单纯乙肝例34例、单纯酒精6例、乙肝合并酒精3例。两组患者的一般资料比较，差异无统计学意义（P>0.05），具有可比性。