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比较非侵入性肝纤维化筛查工具,与银屑病患者甲氨蝶呤累积剂量的关系及相关危险因素。

Comparison of noninvasive screening tools for hepatic fibrosis, association with methotrexate cumulative dose, and risk factors in psoriasis patients.

机构信息

Department of Dermatology, Hospital Pulau Pinang, Penang, Malaysia.

Department of Medicine, Dermatology Unit, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.

出版信息

Dermatol Ther. 2022 Jan;35(1):e15203. doi: 10.1111/dth.15203. Epub 2021 Nov 22.

Abstract

Methotrexate (MTX) is a first-line systemic psoriasis therapy with risk of liver fibrosis. Noninvasive tools for liver fibrosis screening are Fibroscan®, Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio (APRI) index. To compare Fibroscan®, FIB-4, and APRI in detecting fibrosis, determine association of fibrosis with MTX cumulative dose, and explore risk factors for fibrosis. A case-control study involving psoriasis patients aged ≥18 years with MTX cumulative dose ≥1 g, with age and sex-matched MTX naïve psoriasis patients was performed. Noninvasive tools were used to assess liver fibrosis. Sixty-one patients on MTX and 54 controls participated. Fibroscan® detected fibrosis in 22 (36.1%) patients on MTX compared to 11 (19.6%) controls (p = 0.05). FIB-4 predicted fibrosis in 13 (21.3%) patients on MTX and in 10 (17.9%) controls (p = 0.64) while APRI diagnosed 7 (11.5%) versus 7 (12.5%), p = 0.65. No significant correlation between Fibroscan® assessed liver stiffness and MTX cumulative dose (p = 0.47). Independent risk factors for liver fibrosis were MTX use with raised alanine aminotransferase (OR = 68.56, 95% CI 8.26; 568.86, p < 0.001), diabetes mellitus (OR = 30.35, 95% CI 7.52; 122.42, p < 0.001), and raised BMI (obese patients OR = 8.26, 95% CI 1.73-39.43, p = 0.02; overweight patients OR = 6.29, 95% CI 1.28-30.99, p = 0.01). Liver fibrosis occurred in both MTX naïve and MTX-treated psoriasis patients. Fibroscan® detected higher prevalence of liver fibrosis compared to FIB-4 and APRI. Cumulative MTX does not correlate with fibrosis severity. Fibroscan® is recommended prior to MTX therapy and at regular intervals especially among patients with diabetes and increased BMI.

摘要

甲氨蝶呤(MTX)是一种用于治疗银屑病的一线系统性药物,但存在引发肝纤维化的风险。肝纤维化的非侵入性筛查工具包括 Fibroscan®、Fibrosis-4(FIB-4)指数和天门冬氨酸氨基转移酶与血小板比值(APRI)指数。本研究旨在比较 Fibroscan®、FIB-4 和 APRI 在检测肝纤维化方面的作用,确定纤维化与 MTX 累积剂量之间的关联,并探讨纤维化的危险因素。本研究采用病例对照设计,纳入了年龄≥18 岁、MTX 累积剂量≥1g 的银屑病患者(病例组),并按年龄和性别匹配了未接受 MTX 治疗的银屑病患者(对照组)。使用非侵入性工具评估了肝脏纤维化。共有 61 例 MTX 治疗患者和 54 例对照者参与了本研究。结果显示,Fibroscan®检测到 22 例(36.1%)MTX 治疗患者存在纤维化,而对照组为 11 例(19.6%)(p=0.05)。FIB-4 预测 13 例(21.3%)MTX 治疗患者和 10 例(17.9%)对照组存在纤维化(p=0.64),APRI 则分别诊断出 7 例(11.5%)MTX 治疗患者和 7 例(12.5%)对照组存在纤维化(p=0.65)。Fibroscan®评估的肝脏硬度与 MTX 累积剂量之间无显著相关性(p=0.47)。肝纤维化的独立危险因素包括:使用 MTX 治疗伴丙氨酸氨基转移酶升高(OR=68.56,95%CI 8.26;568.86,p<0.001)、糖尿病(OR=30.35,95%CI 7.52;122.42,p<0.001)和升高的 BMI(肥胖患者 OR=8.26,95%CI 1.73-39.43,p=0.02;超重患者 OR=6.29,95%CI 1.28-30.99,p=0.01)。本研究中,MTX 治疗患者和未接受 MTX 治疗的银屑病患者均出现了肝纤维化。与 FIB-4 和 APRI 相比,Fibroscan®检测到的肝纤维化患病率更高。MTX 累积剂量与纤维化严重程度之间无相关性。建议在 MTX 治疗前和治疗期间定期使用 Fibroscan®进行筛查,特别是针对糖尿病和 BMI 升高的患者。

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