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肝储备功能下降增加哌拉西林/他唑巴坦致肝酶异常的风险:一项回顾性病例对照研究

Decreased Hepatic Functional Reserve Increases the Risk of Piperacillin/Tazobactam-Induced Abnormal Liver Enzyme Levels: A Retrospective Case-Control Study.

作者信息

Ooi Hayahide, Asai Yuki, Koriyama Yoshiki, Takahashi Masaaki

机构信息

Department of Pharmacy, National Hospital Organization Mie Chuo Medical Center, Tsu, Japan.

Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, Tsu, Japan.

出版信息

Ann Pharmacother. 2025 Feb;59(2):117-126. doi: 10.1177/10600280241255837. Epub 2024 Jun 5.

Abstract

BACKGROUND

Piperacillin/tazobactam (PIPC/TAZ), which is a combination of a beta-lactam/beta-lactamase inhibitor, often causes liver enzyme abnormalities. The albumin-bilirubin (ALBI) score is a simple index that uses the serum albumin and total bilirubin levels for estimating hepatic functional reserve. Although patients with low hepatic reserve may be at high risk for drug-induced liver enzyme abnormalities, the relationship between PIPC/TAZ-induced abnormal liver enzymes levels and the ALBI score remains unknown.

OBJECTIVE

This study aimed to elucidate the relationship between PIPC/TAZ-induced abnormal liver enzyme levels and the ALBI score.

METHODS

This single-center retrospective case-control study included 335 patients. The primary outcome was PIPC/TAZ-induced abnormal liver enzyme levels. We performed COX regression analysis with male gender, age (≥75 years), alanine aminotransferase level (≥20 IU/L), and ALBI score (≥-2.00) as explanatory factors. To investigate the influence of the ALBI score on the development of abnormal liver enzyme levels, 1:1 propensity score matching between the ≤-2.00 and ≥-2.00 ALBI score groups was performed using the risk factors for drug-induced abnormal liver enzyme levels.

RESULTS

The incidence of abnormal liver enzyme levels was 14.0% (47/335). COX regression analysis revealed that an ALBI score ≥-2.00 was an independent risk factor for PIPC/TAZ-induced abnormal liver enzyme levels (adjusted hazard ratio: 3.08, 95% coefficient interval: 1.207-7.835, = 0.019). After 1:1 propensity score matching, the Kaplan-Meier curve revealed that the cumulative risk for PIPC/TAZ-induced abnormal liver enzyme levels was significantly higher in the ALBI score ≥-2.00 group (n = 76) than in the <-2.00 group (n = 76) ( = 0.033).

CONCLUSION AND RELEVANCE

An ALBI score ≥-2.00 may predict the development of PIPC/TAZ-induced abnormal liver enzyme levels. Therefore, frequent monitoring of liver enzymes should be conducted to minimize the risk of severe PIPC/TAZ-induced abnormal liver enzyme levels in patients with low hepatic functional reserve.

摘要

背景

哌拉西林/他唑巴坦(PIPC/TAZ)是一种β-内酰胺类/β-内酰胺酶抑制剂的组合,常导致肝酶异常。白蛋白-胆红素(ALBI)评分是一种简单的指标,它利用血清白蛋白和总胆红素水平来评估肝功能储备。尽管肝功能储备低的患者可能有较高的药物性肝酶异常风险,但PIPC/TAZ诱导的肝酶水平异常与ALBI评分之间的关系仍不清楚。

目的

本研究旨在阐明PIPC/TAZ诱导的肝酶水平异常与ALBI评分之间的关系。

方法

这项单中心回顾性病例对照研究纳入了335例患者。主要结局是PIPC/TAZ诱导的肝酶水平异常。我们以男性、年龄(≥75岁)、丙氨酸转氨酶水平(≥20 IU/L)和ALBI评分(≥-2.00)作为解释因素进行COX回归分析。为了研究ALBI评分对肝酶水平异常发生的影响,使用药物性肝酶异常水平的危险因素在ALBI评分≤-2.00和≥-2.00组之间进行1:1倾向评分匹配。

结果

肝酶水平异常的发生率为14.0%(47/335)。COX回归分析显示,ALBI评分≥-2.00是PIPC/TAZ诱导的肝酶水平异常的独立危险因素(调整后的风险比:3.08,95%可信区间:1.207-7.835,P = 0.019)。在1:1倾向评分匹配后,Kaplan-Meier曲线显示,ALBI评分≥-2.00组(n = 76)中PIPC/TAZ诱导的肝酶水平异常的累积风险显著高于<-2.00组(n = 76)(P = 0.033)。

结论及意义

ALBI评分≥-2.00可能预测PIPC/TAZ诱导的肝酶水平异常的发生。因此,对于肝功能储备低的患者,应频繁监测肝酶,以将严重的PIPC/TAZ诱导的肝酶水平异常风险降至最低。

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