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监测银屑病患者中氨甲蝶呤诱导的肝纤维化:连续肝活检是否合理?

Monitoring methotrexate-induced hepatic fibrosis in patients with psoriasis: are serial liver biopsies justified?

作者信息

Aithal G P, Haugk B, Das S, Card T, Burt A D, Record C O

机构信息

Queen's Medical Centre University Hospital, Nottingham, UK.

出版信息

Aliment Pharmacol Ther. 2004 Feb 15;19(4):391-9. doi: 10.1046/j.1365-2036.2004.01819.x.

Abstract

BACKGROUND

Reports that up to 26% of subjects with psoriasis develop cirrhosis have led to a recommendation of serial liver biopsies after each cumulative dose of 1500 mg of methotrexate.

AIM

To evaluate the progression of liver injury in patients with psoriasis and the impact of monitoring by liver biopsy on their management.

METHODS

One hundred and twenty-one liver biopsies from 66 subjects (aged 11-79 years) with psoriasis, receiving a median cumulative dose of 3206 mg of methotrexate over a period of 280.5 weeks, were evaluated.

RESULTS

The assessment of advanced fibrosis according to the Ishak system (>or= 4) correlated perfectly with that of the Scheuer system (>or= 3) and poorly with that of the Roenigk scale (>or= 3b) (r2 = 1.0 and 0.31, respectively). Two of 24 pre-treatment biopsies showed advanced fibrosis and both subjects were heavy drinkers. The cumulative probabilities of advanced fibrosis (Ishak >or= 4) were 0%, 2.6%, 2.6%, 8.2% and 8.2% at cumulative doses of 1500, 3000, 4500, 5000 and 6000 mg, respectively. None of the subjects developed cirrhosis during follow-up or discontinued therapy on the basis of liver biopsy findings.

CONCLUSIONS

Advanced hepatic fibrosis with low-dose methotrexate therapy is much less frequent than previously reported. Pre-treatment or monitoring liver biopsies in accordance with the current guidelines have little impact on patient management.

摘要

背景

有报告称,高达26%的银屑病患者会发展为肝硬化,这导致了在每次累积服用1500毫克甲氨蝶呤后建议进行系列肝脏活检。

目的

评估银屑病患者肝损伤的进展情况以及肝脏活检监测对其治疗管理的影响。

方法

对66例(年龄11 - 79岁)银屑病患者的121次肝脏活检进行评估,这些患者在280.5周内接受的甲氨蝶呤累积剂量中位数为3206毫克。

结果

根据Ishak系统(≥4级)对重度纤维化的评估与Scheuer系统(≥3级)的评估完全相关,而与Roenigk分级(≥3b级)的评估相关性较差(r²分别为1.0和0.31)。24次治疗前活检中有2次显示重度纤维化,且这两名患者均为重度饮酒者。在累积剂量为1500、3000、4500、5000和6000毫克时,重度纤维化(Ishak≥4级)的累积概率分别为0%、2.6%、2.6%、8.2%和8.2%。在随访期间,没有患者发展为肝硬化,也没有患者基于肝脏活检结果而停止治疗。

结论

低剂量甲氨蝶呤治疗导致的重度肝纤维化比之前报道的要少见得多。按照当前指南进行治疗前或监测性肝脏活检对患者的治疗管理影响不大。

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