Nyfors A, Poulsen H
Acta Pathol Microbiol Scand A. 1976 May;84(3):262-70.
Eightyeight patients with severe, recalcitrant psoriasis had liver biopsies performed before and after Methotrexate (MTX) therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). A statistically significant increase in the number of pathological post-MTX liver biopsies was found (p less than 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, in all 12.5 per cent, during MTX therapy (95 per cent confidence limits for cirrhosis: 3-14 per cent). There was no statistically significant correlation between the number of pathological post-MTX liver biopsy findings in the 88 patients and the following variables one by one: cumulative dose of MTX, duration of MTX therapy and admitted alcoholic intake during MTX therapy. Cirrhosis and fibrosis did not develop statistically more frequently from pathological than normal pre-MTX liver histology (p = 0.062). The liver damage appeared to be due to a multifactorial interaction of straining factors on the liver during MTX therapy. A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. For use of MTX therapy in psoriasis the following precautions are suggested: MTX therapy should be used only in disabling cases; a pre-MTX liver biopsy and repeat liver biopsies at regular intervals of 1/2-1 year should be performed, alcohol should be prohibited and frequent inquiries should be made about the patient's alcoholic intake; and strong reliance should not be placed on the SGOT as an indicator of abnormal liver histology.
88例重度顽固性银屑病患者在甲氨蝶呤(MTX)治疗前后接受了肝活检。MTX平均给药26个月,采用单次口服给药,每周最大剂量25mg。平均累积剂量为1733mg(范围175 - 4590mg)。发现MTX治疗后肝活检病理改变的数量有统计学显著增加(p小于0.0001)。88例患者中,6例出现肝硬化,另外5例出现纤维化,MTX治疗期间共12.5%(肝硬化的95%置信区间:3 - 14%)。88例患者MTX治疗后肝活检病理结果数量与以下变量逐一比较,均无统计学显著相关性:MTX累积剂量、MTX治疗持续时间以及MTX治疗期间报告的酒精摄入量。肝硬化和纤维化在MTX治疗前病理改变的肝脏组织学基础上发生的频率,与正常肝脏组织学相比,在统计学上并无更频繁的趋势(p = 0.062)。肝损伤似乎是由于MTX治疗期间肝脏承受的多种应激因素相互作用所致。一个多因素指数,包括:MTX累积剂量、MTX治疗期间报告的酒精摄入量、年龄、肥胖程度,以及如有条件,MTX治疗前的肝脏组织学,可用于估计每周口服MTX治疗银屑病期间发生肝硬化或纤维化的概率。对于MTX治疗银屑病,建议采取以下预防措施:MTX治疗仅应用于致残性病例;应在MTX治疗前进行肝活检,并每隔半年至1年定期重复肝活检;应禁止饮酒,并经常询问患者的酒精摄入量;不应过度依赖谷草转氨酶(SGOT)作为肝脏组织学异常的指标。