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前蛋白转化酶枯草杆菌蛋白酶/克新9型(PCSK-9)抑制剂所致肝损伤——一项回顾性分析

Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis.

作者信息

Zafar Yousuf, Sattar Yasar, Ullah Waqas, Roomi Sohaib, Rashid Mamoon-Ur-, Khan Muhammad Shayan, Schmidt Laura

机构信息

Internal Medicine, University of Missouri, Kansas City, MO, USA.

Internal Medicine, Icahn School of Medicine at Mount Sinai-Elmhurst Hospital, New York, NY, USA.

出版信息

J Community Hosp Intern Med Perspect. 2020 Feb 10;10(1):32-37. doi: 10.1080/20009666.2019.1710952. eCollection 2020.


DOI:10.1080/20009666.2019.1710952
PMID:32128056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7034434/
Abstract

: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature. : A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, or chronic secondary liver diseases causing liver injury were taken into consideration. Exclusion criteria included patients without dyslipidemia. : The mean age of the study population was 64 ± 11 years (63% males and 37% females). The lipid profile including triglyceride and cholesterol levels during 6-month follow-up visit showed a mean of 184 ± 260 and 163 ± 50 mg/dL as compared to that at baseline of 227 ± 603 and 181 ± 70 mg/dL, respectively. In terms of clinical efficacy, a 6-month follows-up showed a drop in triglyceride and cholesterol levels by 38 and 15 mg/dL, respectively. A liver function test at 6 months in patients taking PCSK-9 inhibitors showed an increase in alanine transaminase (ALT) and aspartate transaminase (AST) by 5.8 mg/dL ( = 0.037) and 6.2 mg/dL ( = 0.008), respectively, from baseline values. : PCSK-9 inhibitors should be used cautiously with a follow-up liver function test.

摘要

前蛋白转化酶枯草溶菌素/克新9型(PCSK-9)抑制剂在有或无既往肝损伤的患者中均可诱发肝功能障碍,而既往文献对此讨论不足。:2015年至2018年期间,根据预先设定的选择标准,对密苏里大学堪萨斯城分校的202例患者进行了回顾性研究。纳入标准包括患有血脂异常的患者,无论是否使用PCSK-9抑制剂,均需在基线和平均6个月随访时进行肝功能检查和血脂分析。考虑了年龄、性别以及其他药物(他汀类药物、口服抗糖尿病药物和抗高血压药物)诱导的或导致肝损伤的慢性继发性肝病等混杂因素。排除标准包括无血脂异常的患者。:研究人群的平均年龄为64±11岁(男性占63%,女性占37%)。6个月随访期间的血脂分析,包括甘油三酯和胆固醇水平,与基线时的227±603和181±70mg/dL相比,平均值分别为184±260和163±50mg/dL。在临床疗效方面,6个月的随访显示甘油三酯和胆固醇水平分别下降了38和15mg/dL。服用PCSK-9抑制剂的患者在6个月时的肝功能检查显示,谷丙转氨酶(ALT)和谷草转氨酶(AST)分别比基线值升高了5.8mg/dL(P = 0.037)和6.2mg/dL(P = 0.008)。:使用PCSK-9抑制剂时应谨慎,并进行肝功能随访检查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1279/7034434/91ec1626224a/ZJCH_10_1710952_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1279/7034434/91ec1626224a/ZJCH_10_1710952_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1279/7034434/91ec1626224a/ZJCH_10_1710952_F0001_OC.jpg

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[10]
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J Lipid Atheroscler. 2025-1

[2]
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[3]
PCSK9 Inhibitor: Safe Alternative to Fill the Treatment Gap in Statin-Limited Conditions?

Rev Cardiovasc Med. 2022-11-9

[4]
D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.

Anal Cell Pathol (Amst). 2023

[5]
Sex difference in circulating PCSK9 and its clinical implications.

Front Pharmacol. 2022-9-7

[6]
Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats.

Int J Mol Sci. 2022-7-2

[7]
Effects of proprotein convertase subtilisin/kexin type-9 inhibitors on fatty liver.

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[8]
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本文引用的文献

[1]
Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial.

Lancet Diabetes Endocrinol. 2019-7-1

[2]
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World J Cardiol. 2017-2-26

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The Role of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in the Management of Dyslipidemia.

Curr Pharm Des. 2017

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