LIGHT AND ELECTRON-MICROSCOPIC ANALYSIS OF SEQUENTIAL LIVER-BIOPSY SAMPLES FROM RHEUMATOID-ARTHRITIS PATIENTS RECEIVING LONG-TERM METHOTREXATE THERAPY - FOLLOWUP OVER LONG TREATMENT INTERVALS AND CORRELATION WITH CLINICAL AND LABORATORY VARIABLES
LIGHT AND ELECTRON-MICROSCOPIC ANALYSIS OF SEQUENTIAL LIVER-BIOPSY SAMPLES FROM RHEUMATOID-ARTHRITIS PATIENTS RECEIVING LONG-TERM METHOTREXATE THERAPY - FOLLOWUP OVER LONG TREATMENT INTERVALS AND CORRELATION WITH CLINICAL AND LABORATORY VARIABLES
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DOI：
10.1002/art.1780380904
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发表时间：
1995-09-01
影响因子：
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通讯作者：
AXIOTIS, CA
中科院分区：
文献类型：
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作者：
KREMER, JM;KAYE, GI;AXIOTIS, CA
目的，描述接受长期甲氨蝶呤 (MTX) 治疗的类风湿性关节炎 (RA) 患者的前瞻性研究队列的肝脏组织病理学特征和超微结构变化，并寻求这些变化与同时测量的肝功能实验室指标之间的相关性。方法，这是一项长期、前瞻性、开放观察性研究，27 名开始接受 MTX 治疗并继续长期治疗的 RA 门诊患者接受了基线和随访肝活检，100 例通过光学显微镜 (Lh?I) 分析了 70 份肝活检标本，并根据改良的 Roenigk 评分和新设计的数字分级系统进行了评估，还通过电子显微镜 (EM) 分析了 93 份肝活检标本，每隔 4-6 周采集一次血样，测定胆红素、碱性磷酸酶、天冬氨酸转氨酶 (AST) 和白蛋白水平，如果 AST 或异常，则调整 MTX 的每周剂量。白蛋白水平，在平均 8.2 年（范围 2-13 年）的随访期内，每名患者平均获得 6.3 次肝活检。 结果，第 3 年时，改良 Roenigk 评分与基线显着不同，第 3 年，该评分从平均值 1.8 增加至 2.3（P = 0.05），第 6 年，该评分增加至 2.4（P = 0.04），但临床上并未考虑到这一点有意义，任何 LM 分级系统均未观察到与基线相比的其他显着变化，在调查过程中 EM 未观察到显着进展，AST 连续测量值的增加与改良 Roenigk 评分 (r = 0.21，P = 0.016) 和数字评分 (r = 0.19，P = 0.027) 相关。结论，接受每周单剂量口服 MTX 治疗的 RA 患者的病情几乎没有恶化当根据 AST 和血清白蛋白异常调整药物剂量时，通过 LM 或 EM 观察肝结构，并定期监测。
Objective, To describe liver histopathologic features and ultrastructural changes in a prospectively studied cohort of rheumatoid arthritis (RA) patients receiving long-term methotrexate (MTX) therapy, and to seek correlations between these changes and simultaneously measured laboratory indices of liver function.Methods, This was a long-term, prospective, open observational study, Twenty-seven outpatients with RA who began therapy with MTX and continued treatment for extended periods underwent baseline and followup liver biopsies, One hundred seventy liver biopsy specimens were analyzed by light microscopy (Lh?I) and assessed according to a modified Roenigk score and a newly devised numerical grading system, Ninety-three biopsy specimens were also analyzed by electron microscopy (EM), Blood samples were obtained at 4-6-week intervals for determination of bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), and albumin levels, and the weekly dosage of MTX was adjusted if there were abnormalities in the AST or albumin level, A mean of 6.3 liver biopsies per patient were obtained over a mean followup period of 8.2 years (range 2-13 years).Results, The modified Roenigk score was significantly different from baseline at year 3, when it increased from a mean of 1.8 to 2.3 (P = 0.05) and at year 6, when it increased to 2.4 (P = 0.04), but this was not considered clinically meaningful, No other significant changes from baseline were observed by either LM grading system, No significant progression was observed by EM over the course of the investigation, Increases in serial measurements of AST correlated with both the modified Roenigk score (r = 0.21, P = 0.016) and the numerical rating score (r = 0.19, P = 0.027).Conclusion, Patients with RA who are receiving weekly single-dose oral MTX therapy exhibit little deterioration in hepatic architecture by LM or EM when the dosage of the drug is adjusted for abnormalities in AST and serum albumin, monitored at frequent intervals.