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类风湿关节炎患者使用羟氯喹啉后非酒精性脂肪性肝炎的患病率及相关危险因素:一项基于人群的研究

PREVALENCE AND RISK FACTORS ASSOCIATED WITH NON-ALCOHOLIC STEATOHEPATITIS IN PATIENTS WITH RHEUMATOID ARTHRITIS ON HYDROXYCHLOROQUINE: A POPULATION-BASED STUDY.

作者信息

Boustany Antoine, Onwuzo Somtochukwu, Johnson Adejoke, Farhat David, Najjar Mimi, Zeid Hadi Khaled Abou, Onwuzo Chidera N, Abu-Hammour Mohamad-Noor, Abdel-Razeq Rashid, Mohamed Islam, Eren Barish, Asaad Imad

机构信息

Division of Gastroenterology, Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida, USA.

Department of Gastroenterology and Hepatology, Allegheny Health Network, Pittsburg, Pennsylvania, USA.

出版信息

Arq Gastroenterol. 2025 Apr 4;62:e24100. doi: 10.1590/S0004-2803.24612024-100. eCollection 2025.

DOI:10.1590/S0004-2803.24612024-100
PMID:40197885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12043191/
Abstract

BACKGROUND

Non-alcoholic steatohepatitis (NASH) is becoming a leading cause of liver disease in the US, while Rheumatoid arthritis (RA) affects a significant portion of the global population. In recent times, newer drugs have been developed to slow down the progression of RA, one of which is hydroxychloroquine (HCQ). Despite HCQ being linked to slowly progressive transaminitis, its role in the development of NASH remains unclear. Our research fills this gap by examining the prevalence and risk factors of developing NASH in patients with RA on HCQ.

METHODS

This retrospective cohort study analyzed 619,350 adult patients diagnosed with RA. Data were sourced from a multicenter database covering over 360 hospitals across 26 healthcare systems in the US from 1999 to September 2022, excluding pregnant individuals. Multivariate regression analysis assessed the risk of NASH, adjusting for confounders including smoking history, male gender, dyslipidemia, hypertension, type 2 diabetes mellitus, obesity, and hydroxychloroquine use. Statistical significance was set at P<0.05, with analyses conducted using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008).

RESULTS

In a cohort of 79.4 million individuals, 619,350 non-pregnant subjects had rheumatoid arthritis, with 3,080 diagnosed with NASH, while 616,270 did not. Patients with NASH displayed a higher prevalence of smoking history, hyperlipidemia, hypertension, type 2 diabetes mellitus, obesity, and HCQ use. Multivariate regression analysis identified increased NASH risk in smokers (OR: 1.24; 95%CI: 1.14-1.36), males (OR: 0.88; 95%CI: 0.81-0.96), individuals with dyslipidemia (OR: 1.34; 95%CI: 1.21-1.47), hypertension (OR: 1.11; 95%CI: 1.00-1.27), type 2 diabetes mellitus (OR: 3.24; 95%CI: 2.98-3.54), obesity (OR: 3.59; 95%CI: 3.31-3.89), and hydroxychloroquine use (OR: 1.79; 95%CI: 1.65-1.94).

CONCLUSION

RA patients on HCQ showed an increased prevalence and odds of developing NASH, even after adjusting for common confounding factors. This indicates that HCQ may play a role in the development of hepatic steatosis and fibrosis. Clinicians should consider this association to prevent advanced liver disease. Future research should focus on optimal screening for early detection and enhancing patient outcomes.

BACKGROUND

• The study investigates the relationship between nonalcoholic steatohepatitis (NASH) and rheumatoid arthritis (RA), analyzing the impact of hydroxychloroquine (HCQ) use on the development of NASH.

BACKGROUND

• HCQ slows the progression of RA; however, its effect on the liver is not yet fully understood.

BACKGROUND

• This multicenter retrospective cohort study analyzed 619,350 adult patients diagnosed with RA.

BACKGROUND

• RA patients on HCQ showed an increased prevalence and higher odds of developing NASH. This association should be considered to prevent advanced liver disease.

摘要

背景

非酒精性脂肪性肝炎(NASH)正成为美国肝病的主要病因,而类风湿关节炎(RA)影响着全球相当一部分人口。近年来,已开发出新型药物来减缓RA的进展,其中之一是羟氯喹(HCQ)。尽管HCQ与缓慢进展的转氨酶升高有关,但其在NASH发生中的作用仍不清楚。我们的研究通过检查使用HCQ的RA患者中NASH的患病率和危险因素填补了这一空白。

方法

这项回顾性队列研究分析了619350例诊断为RA的成年患者。数据来自一个多中心数据库,该数据库涵盖了1999年至2022年9月美国26个医疗系统中360多家医院的数据,不包括孕妇。多变量回归分析评估了NASH的风险,并对包括吸烟史、男性、血脂异常、高血压、2型糖尿病、肥胖和使用羟氯喹在内的混杂因素进行了调整。统计学显著性设定为P<0.05,使用R 4.0.2版本(R统计计算基金会,奥地利维也纳,2008年)进行分析。

结果

在7940万个体的队列中,619350例非孕妇患有类风湿关节炎,其中3080例被诊断为NASH,而616270例未患NASH。NASH患者的吸烟史、高脂血症、高血压、2型糖尿病、肥胖和使用HCQ的患病率更高。多变量回归分析确定吸烟者(比值比:1.24;95%置信区间:1.14-1.36)、男性(比值比:0.88;95%置信区间:0.81-0.96)、血脂异常者(比值比:1.34;95%置信区间:1.21-1.47)、高血压患者(比值比:1.11;95%置信区间:1.00-1.27)、2型糖尿病患者(比值比:3.24;95%置信区间:2.98-3.54)、肥胖者(比值比:3.59;95%置信区间:3.31-3.89)和使用羟氯喹者(比值比:1.79;95%置信区间:1.65-1.94)患NASH的风险增加。

结论

即使在调整了常见的混杂因素后,使用HCQ的RA患者发生NASH的患病率和几率也有所增加。这表明HCQ可能在肝脂肪变性和纤维化的发生中起作用。临床医生应考虑这种关联以预防晚期肝病。未来的研究应侧重于优化早期检测的筛查并改善患者预后。

背景

• 本研究调查了非酒精性脂肪性肝炎(NASH)与类风湿关节炎(RA)之间的关系,分析了使用羟氯喹(HCQ)对NASH发生的影响。

背景

• HCQ可减缓RA的进展;然而,其对肝脏的影响尚未完全了解。

背景

• 这项多中心回顾性队列研究分析了619350例诊断为RA的成年患者。

背景

• 使用HCQ的RA患者发生NASH的患病率增加且几率更高。应考虑这种关联以预防晚期肝病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e60/12043191/07b58ef3726e/1678-4219-ag-62-e24100-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e60/12043191/07b58ef3726e/1678-4219-ag-62-e24100-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e60/12043191/07b58ef3726e/1678-4219-ag-62-e24100-gf1.jpg

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Hydroxychloroquine Effects on THP-1 Macrophage Cholesterol Handling: Cell Culture Studies Corresponding to the TARGET Cardiovascular Trial.羟氯喹对 THP-1 巨噬细胞胆固醇处理的影响:与 TARGET 心血管试验相对应的细胞培养研究。
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