vanDooren-Greebe R J, Kuijpers A L, Buijs W C, Kniest P H, Corstens F H, Nagengast F M, de Boo T, Willems J L, Duller P, van de Kerkhof P C
Department of Dermatology, University Hospital Nijmegen, Netherlands.
Br J Dermatol. 1996 Mar;134(3):481-7.
Oral methotrexate (MTX) is a highly effective drug for the treatment of severe psoriasis. A limitation of this treatment is its potential hepatotoxicity. In the present prospective study the value of dynamic hepatic scintigraphy (DHS) and serum aminoterminal propeptide of type III procollagen (PIIINP) were investigated as screening methods for early detection of MTX-induced hepatic damage. These relatively non-invasive procedures were compared with the liver biopsy classification, until now the gold standard to assess MTX-induced liver damage. Twenty-five MTX patients were studied. The mean cumulative MTX dose was 3.9 g (range 0.2-11.1 g). Twenty-one patients had a normal liver histology (grade I), three patients had steatosis (grade II), and one patient mild fibrosis (grade IIIA). Seven additional patients with non-MTX related hepatic cirrhosis were included as disease controls. DHS showed a clear-cut separation between the portal contribution of the MTX patients with grade I liver histology, and that of all other patients. A portal contribution larger than 52% was associated with a > 95% chance of normal liver histology. If this cut-off value had been used to postpone the liver biopsy, this would have resulted in at least a 55% reduction in the number of biopsies in patients with a normal liver histology. DHS appeared to be very promising as a screening test to differentiate between the presence or absence of MTX-induced hepatic damage, but appeared not suitable to grade the severity of hepatic damage. Although a global relationship was demonstrated between serum PIIINP concentration and hepatic damage, single measurements in individual patients were not reliable. The combination of PIIINP measurements with DHS had only a limited additional value above DHS alone. The present study indicates that DHS has great promise for the detection of early MTX-induced hepatic damage. Pending further studies, regular liver biopsies remain mandatory for the safe prolonged use of MTX in psoriasis patients.
口服甲氨蝶呤（MTX）是治疗重度银屑病的一种高效药物。这种治疗方法的一个局限性是其潜在的肝毒性。在本前瞻性研究中，对动态肝脏闪烁扫描（DHS）和血清III型前胶原氨基端前肽（PIIINP）作为早期检测MTX所致肝损伤的筛查方法的价值进行了研究。将这些相对非侵入性的检查方法与肝活检分级进行比较，到目前为止肝活检分级是评估MTX所致肝损伤的金标准。对25例使用MTX的患者进行了研究。MTX的平均累积剂量为3.9 g（范围0.2 - 11.1 g）。21例患者肝脏组织学正常（I级），3例患者有脂肪变性（II级），1例患者有轻度纤维化（IIIA级）。另外纳入7例非MTX相关性肝硬化患者作为疾病对照。DHS显示肝脏组织学I级的MTX患者的门静脉贡献与所有其他患者的门静脉贡献有明显区分。门静脉贡献大于52%与肝脏组织学正常的可能性> 95%相关。如果使用这个临界值来推迟肝活检，这将导致肝脏组织学正常的患者的活检数量至少减少55%。DHS作为区分是否存在MTX所致肝损伤的筛查试验似乎非常有前景，但似乎不适合对肝损伤的严重程度进行分级。虽然血清PIIINP浓度与肝损伤之间存在总体关系，但对个体患者的单次测量不可靠。PIIINP测量与DHS联合使用仅比单独使用DHS有有限增加的价值。本研究表明DHS在检测早期MTX所致肝损伤方面很有前景。在进一步研究之前，对于银屑病患者安全长期使用MTX，定期肝活检仍然是必需的。
