Boffa M J, Smith A, Chalmers R J, Mitchell D M, Rowan B, Warnes T W, Shomaf M, Haboubi N Y
Dermatology Centre, University of Manchester School of Medicine, U.K.
Br J Dermatol. 1996 Oct;135(4):538-44.
This study was designed to establish whether measurement of a serological marker of fibrosis might reduce the need for liver biopsy in psoriatic patients receiving methotrexate (MTX). Levels of type III procollagen aminopeptide (PIIINP-O and PIIINP-B) and laminin P1 (LamP1-B) were measured in 147 serum samples taken at the time of liver biopsy in 87 patients receiving long-term MTX treatment for severe psoriasis. Biopsies were classified as: (1) normal, (2) steatosis, (3) inflammation, (4) fibrosis, or (5) cirrhosis. Groups 3-5 were considered to show clinically relevant abnormality. Compared with controls, PIIINP-O was significantly raised in the group of MTX-treated psoriatics (P < 0.001). Within this group, levels were significantly higher in patients with inflammation, fibrosis or cirrhosis compared with those with normal histology or steatosis alone (P < 0.0001). In contrast, PIIINP-B and LamP1-B did not distinguish between controls and MTX-treated patients or between histological groups. Forty-two patients had two or more biopsies with simultaneous PIIINP-O measurement. PIIINP-O levels at the time of the first biopsy were normal in six of the seven patients whose histology was initially normal and subsequently became abnormal. A single measurement of PIIINP-O thus did not predict which patients might develop abnormal histology following further MTX. In a group of 17 patients, PIIINP-O was measured 3-monthly for up to 6 years during MTX treatment. PIIINP-O was elevated at some time during follow-up in all three patients who developed abnormal histology but was consistently normal in eight of the 11 patients whose histology remained or became normal. Our findings indicate that PIIINP-O is of value in detecting liver damage and, particularly if measured serially, may reduce the need for liver biopsy in MTX-treated patients. Although the test does not detect all patients with fibrosis, it would appear that the risk of missing significant liver damage in patients with persistently normal PIIINP-O is low.
本研究旨在确定对纤维化血清学标志物的检测是否可减少接受甲氨蝶呤(MTX)治疗的银屑病患者进行肝活检的必要性。对87例因严重银屑病接受长期MTX治疗的患者在肝活检时采集的147份血清样本,检测了III型前胶原氨基肽(PIIINP - O和PIIINP - B)及层粘连蛋白P1(LamP1 - B)的水平。活检结果分为:(1)正常,(2)脂肪变性,(3)炎症,(4)纤维化,或(5)肝硬化。3 - 5组被认为显示有临床相关异常。与对照组相比,接受MTX治疗的银屑病患者组中PIIINP - O显著升高(P < 0.001)。在该组中,与组织学正常或仅有脂肪变性的患者相比,炎症、纤维化或肝硬化患者的水平显著更高(P < 0.0001)。相比之下,PIIINP - B和LamP1 - B在对照组和接受MTX治疗的患者之间或组织学组之间无区分作用。42例患者进行了两次或更多次活检并同时检测PIIINP - O。7例组织学最初正常随后变为异常的患者中,有6例首次活检时PIIINP - O水平正常。因此,单次检测PIIINP - O并不能预测哪些患者在进一步接受MTX治疗后可能出现组织学异常。在一组17例患者中,在MTX治疗期间每3个月检测一次PIIINP - O,长达6年。3例出现组织学异常的患者在随访期间的某个时间PIIINP - O升高,但11例组织学保持正常或变为正常的患者中有8例PIIINP - O始终正常。我们的研究结果表明,PIIINP - O在检测肝损伤方面有价值,特别是如果进行连续检测,可能会减少接受MTX治疗患者的肝活检需求。虽然该检测不能检测出所有纤维化患者,但似乎PIIINP - O持续正常的患者漏诊严重肝损伤的风险较低。