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甲氨蝶呤治疗与类风湿关节炎患者肝硬度和显著肝纤维化增加无关:实时二维剪切波弹性成像的横断面对照研究。

Methotrexate therapy is not associated with increased liver stiffness and significant liver fibrosis in rheumatoid arthritis patients: A cross-sectional controlled study with real-time two-dimensional shear wave elastography.

机构信息

Dipartimento di Specialità Mediche, UOC Reumatologia, Azienda Ospedaliero-Universitaria, Viale San Pietro 8, 07100 Sassari, Italy.

Università degli Studi di Sassari, Piazza Università 21, 07100 Sassari, Italy.

出版信息

Eur J Intern Med. 2019 Nov;69:57-63. doi: 10.1016/j.ejim.2019.08.022. Epub 2019 Aug 29.

Abstract

OBJECTIVE

To explore the significance of the association between treatment with methotrexate (MTX) and liver stiffness in rheumatoid arthritis (RA) patients.

METHODS

We enrolled 140 consecutive RA patients under MTX treatment (MTX-treated RA; mean treatment duration: 6.2 years; mean MTX cumulative dose: 4.67 g), 33 RA patients naive to MTX (MTX-naive RA) and 100 age and sex-matched healthy blood donors (HD). Liver stiffness was assessed by real time two-dimensional shear wave elastography, with values ≥7.1 Kilopascals (kPa) defining significant liver fibrosis.

RESULTS

kPa values in HD (4.32 ± 0.7) were lower than that in MTX-naive RA (4.92 ± 0.8) and MTX-treated RA (4.85 ± 0.9, p < .0005 for trend). On the contrary, the difference in kPa between MTX-naive and MTX-treated RA was not significant (p = .89). Similarly, liver stiffness was not significantly different across strata of cumulative MTX dose (4.95 ± 0.7 kPa in MTX <1 g, 4.90 ± 1.1 kPa in MTX 1-3 g and 4.80 ± 0.9 in MTX >3 g, p = .610). Significant liver fibrosis was diagnosed in 4 patients in the MTX-treated RA (highest kPa value = 7.6; no liver function test abnormalities or clinical signs of hepatic failure) and in none in both the MTX-naive RA and HD groups (p = .145).

CONCLUSION

Liver stiffness values, although within the normal range, are significantly higher in RA patients vs. controls, irrespective of MTX treatment. RA patients taking MTX do not have a higher prevalence of significant liver fibrosis when compared to MTX naive RA patients and the general population.

摘要

目的

探讨甲氨蝶呤(MTX)治疗与类风湿关节炎(RA)患者肝硬度之间关联的意义。

方法

我们纳入了 140 例接受 MTX 治疗的连续 RA 患者(MTX 治疗 RA;平均治疗时间:6.2 年;平均 MTX 累积剂量:4.67g)、33 例 MTX 初治 RA 患者和 100 例年龄和性别匹配的健康献血者(HD)。通过实时二维剪切波弹性成像评估肝硬度,kPa 值≥7.1 定义为显著肝纤维化。

结果

HD(4.32±0.7)的 kPa 值低于 MTX 初治 RA(4.92±0.8)和 MTX 治疗 RA(4.85±0.9,p<0.0005 趋势)。相反,MTX 初治和 MTX 治疗 RA 之间的 kPa 值差异无统计学意义(p=0.89)。同样,累积 MTX 剂量分层之间的肝硬度也无显著差异(MTX<1g 组为 4.95±0.7kPa,MTX 1-3g 组为 4.90±1.1kPa,MTX>3g 组为 4.80±0.9kPa,p=0.610)。在 MTX 治疗 RA 中诊断出 4 例患者存在显著肝纤维化(最高 kPa 值=7.6;无肝功能试验异常或肝衰竭的临床征象),而 MTX 初治 RA 和 HD 组均无患者存在显著肝纤维化(p=0.145)。

结论

RA 患者的肝硬度值尽管在正常范围内,但与对照组相比仍显著升高,而与 MTX 治疗无关。与 MTX 初治 RA 患者和普通人群相比,接受 MTX 治疗的 RA 患者并无更高的显著肝纤维化患病率。

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