Treatment of primary biliary cirrhosis with low-dose weekly methotrexate.
Treatment of primary biliary cirrhosis with low-dose weekly methotrexate.
复制标题
每周低剂量甲氨蝶呤治疗原发性胆汁性肝硬化。
DOI：
10.1016/0016-5085(91)90085-y
复制
发表时间：
1991
期刊：
影响因子：
29.4
通讯作者：
Knox,TA
中科院分区：
文献类型：
--
作者：
Kaplan,MM;Knox,TA
9例有症状的原发性胆汁性肝硬化患者口服甲氨蝶呤15 mg/周，持续12-34个月。3名女性出现瘙痒，2名女性出现疲劳，4名女性出现瘙痒和疲劳。在开始甲氨蝶呤治疗后4-11个月内，瘙痒消失，疲劳减轻或全部消失。所有瘙痒的患者都可以停用消胆胺（5种）或抗组胺药（2种）。所有患者的肝功能生化检查均有所改善，当甲氨蝶呤停药或剂量降低时，有3例患者的肝功能恶化。平均血清碱性磷酸酶从471 U/L降至171 U/L（P< 0.01），血清胆红素从0.99 mg/dL降至0.59 mg/dL（P< 0.05），血清丙氨酸氨基转移酶从132 U/L降至61 U/L（P= 0.02），血清胆固醇从265 mg/dL降至213 mg/dL（NS）。如果仅使用基线血清胆固醇水平升高的6名妇女的数据，则血清胆固醇的降低是显著的，P= 0.05。所有患者的血清白蛋白均保持正常。血清胆红素水平升高的4例患者中有3例恢复正常。4例患者血清碱性磷酸酶水平恢复正常，3例患者丙氨酸氨基转移酶水平恢复正常。根据编码肝活检标本的定量评价，5例患者的肝组织学改善，其余4例稳定。组织学改善主要是由于门静脉炎症和胆管损伤减少。7例患者抗线粒体抗体滴度降低。这些数据表明，甲氨蝶呤可能是治疗原发性胆汁性肝硬化的有效方法。需要对照试验来评估长期疗效和毒性。
Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12–34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4–11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P< 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P< 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P= 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant,P= 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.