前蛋白转化酶枯草溶菌素/kexin 9型抑制剂对脂肪肝的影响。
Effects of proprotein convertase subtilisin/kexin type-9 inhibitors on fatty liver.
作者信息
Shafiq Muhammad, Walmann Timothy, Nutalapati Venkat, Gibson Cheryl, Zafar Yousaf
机构信息
General and Geriatric Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States.
Department of Diagnostic Radiology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
出版信息
World J Hepatol. 2020 Dec 27;12(12):1258-1266. doi: 10.4254/wjh.v12.i12.1258.
BACKGROUND
Many studies have investigated the progression of nonalcoholic fatty liver disease (NAFLD) and its predisposing risk factors, but the conclusions from these studies have been conflicting. More challenging is the fact that no effective treatment is currently available for NAFLD.
AIM
To determine the effects of proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors on fatty infiltration of the liver.
METHODS
This retrospective, chart review-based study was conducted on patients, 18-year-old and above, who were currently on PCSK9 inhibitor drug therapy. Patients were excluded from the study according to missing pre- or post-treatment imaging or laboratory values, presence of cirrhosis or rhabdomyolysis, or development of acute liver injury during the PCSK9 inhibitor treatment period; the latter being due to false elevation of liver function markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Radiographic improvement was assessed by a single radiologist, who read both the pre- and post-treatment images to minimize reading bias. Fatty infiltration of the liver was also assessed by changes in ALT and AST, with pre- and post-treatment levels compared by paired -test (alpha criterion: 0.05).
RESULTS
Of the 29 patients included in the study, 8 were male (27.6%) and 21 were female (72.4%). Essential hypertension was present in 25 (86.2%) of the patients, diabetes mellitus in 18 (62.1%) and obesity in 15 (51.7%). In all, patients were on PCSK9 inhibitors for a mean duration of 23.69 ± 11.18 mo until the most recent ALT and AST measures were obtained. Of the 11 patients who received the radiologic diagnosis of hepatic steatosis, 8 (72.73%) achieved complete radiologic resolution upon use of PCSK9 inhibitors (mean duration of 17.6 mo). On average, the ALT level (IU/L) decreased from 21.83 ± 11.89 at pretreatment to 17.69 ± 8.00 at post-treatment (2-tailed = 0.042) and AST level (IU/L) decreased from 22.48 ± 9.00 pretreatment to 20.59 ± 5.47 post-treatment (2-tailed = 0.201).
CONCLUSION
PCSK9 inhibitors can slow down or even completely resolve NAFLD.
背景
许多研究已经调查了非酒精性脂肪性肝病（NAFLD）的进展及其诱发风险因素，但这些研究得出的结论相互矛盾。更具挑战性的是，目前尚无针对NAFLD的有效治疗方法。
目的
确定前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）抑制剂对肝脏脂肪浸润的影响。
方法
这项基于图表回顾的回顾性研究针对18岁及以上正在接受PCSK9抑制剂药物治疗的患者进行。根据治疗前或治疗后的影像学或实验室检查值缺失、存在肝硬化或横纹肌溶解症、或在PCSK9抑制剂治疗期间发生急性肝损伤（后者是由于肝功能标志物丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的假性升高）将患者排除在研究之外。由一名放射科医生评估影像学改善情况，该医生阅读治疗前和治疗后的图像以尽量减少阅读偏差。还通过ALT和AST的变化评估肝脏脂肪浸润情况，通过配对t检验比较治疗前和治疗后的水平（α标准：0.05）。
结果
纳入研究的29例患者中，男性8例（27.6%），女性21例（72.4%）。25例（86.2%）患者患有原发性高血压，18例（62.1%）患有糖尿病，15例（51.7%）患有肥胖症。总体而言，在获得最近的ALT和AST测量值之前，患者接受PCSK9抑制剂治疗的平均持续时间为23.69±11.18个月。在接受肝脏脂肪变性放射学诊断的11例患者中，8例（72.73%）在使用PCSK9抑制剂后实现了完全的放射学缓解（平均持续时间为17.6个月）。平均而言，ALT水平（IU/L）从治疗前的21.83±11.89降至治疗后的17.69±8.00（双侧t检验P = 0.042），AST水平（IU/L）从治疗前的22.48±9.00降至治疗后的20.59±5.47（双侧t检验P = 0.201）。
结论
PCSK9抑制剂可以减缓甚至完全解决NAFLD。
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