González-Koch A, Brahm J, Antezana C, Smok G, Cumsille M A
Gastroenterology Center, University of Chile Clinical Hospital, Santiago.
J Hepatol. 1997 Jul;27(1):143-9. doi: 10.1016/s0168-8278(97)80294-2.
BACKGROUND/AIMS: Many therapies have been tried in primary biliary cirrhosis. It has been suggested that a combination of ursodeoxycholic acid and methotrexate may offer advantages. Because the benefit and safety of this combination is uncertain, we conducted this prospective, randomized, double-blind, controlled trial.
Twenty-five patients with well-defined primary biliary cirrhosis were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48 weeks. Clinical, biochemical and histologic evolution were assessed.
In both groups the clinical response was similar and heterogeneous. In patients of ursodeoxycholic acid alone group, biochemical and histologic changes were comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48 weeks. The addition of methotrexate was not associated with substantial adverse affects.
The use of methotrexate in combination with ursodeoxycholic acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor was substantial toxicity added. Unless larger and longer controlled trials with clinical, biochemical and histologic controls show it to be a safe and effective therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should not be used as a proven and accepted treatment.
背景/目的：在原发性胆汁性肝硬化中已尝试了多种治疗方法。有人提出熊去氧胆酸和甲氨蝶呤联合使用可能具有优势。由于这种联合治疗的益处和安全性尚不确定，我们进行了这项前瞻性、随机、双盲、对照试验。
25例明确诊断为原发性胆汁性肝硬化的患者被随机分配接受熊去氧胆酸（500毫克/天）加甲氨蝶呤（10毫克/周）或熊去氧胆酸加安慰剂治疗48周。评估临床、生化和组织学变化。
两组的临床反应相似且存在差异。在单用熊去氧胆酸组的患者中，48周时的生化和组织学变化与熊去氧胆酸加甲氨蝶呤组的患者相当。添加甲氨蝶呤未产生明显不良反应。
甲氨蝶呤与熊去氧胆酸联合使用并未比单用熊去氧胆酸带来额外益处，也未增加明显毒性。除非有更大规模、更长时间且有临床、生化和组织学对照的对照试验表明其对原发性胆汁性肝硬化是一种安全有效的治疗方法，否则熊去氧胆酸加甲氨蝶呤不应作为已证实且被接受的治疗方法使用。
