Bergasa N V, Jones A, Kleiner D E, Rabin L, Park Y, Wells M C, Hoofnagle J H
Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Am J Gastroenterol. 1996 Feb;91(2):295-9.
To assess the efficacy of low doses of oral methotrexate as therapy for primary biliary cirrhosis.
Ten symptomatic patients with this disease were treated with methotrexate at a dose of 15 mg/wk in an open label trial.
Eight patients completed 1 yr of treatment and six completed 2. Pruritus and fatigue decreased in all patients treated for at least 1 yr. Mean levels of serum alkaline phosphatase, ALT, and IgM were less at 1 and 2 yr than corresponding baseline means. Total serum bilirubin increased in three patients during treatment. Serum aminotransferases and alkaline phosphatase became normal in one patient with stage I disease. Although liver biopsies at 1 and 2 yr revealed a decrease in the intensity of the inflammatory infiltrate, they also showed an increase in fibrosis suggestive of disease progression. Methotrexate was discontinued in five patients: for disease progression in four (one at 4 months, one at 1 yr, and two at 2 yr) and for intractable pruritus in one (at 4 months). All patients experienced transient mucositis and intermittent dyspepsia.
These findings suggest that methotrexate treatment in patients with primary biliary cirrhosis is not beneficial in patients with advanced disease; in patients with early disease, methotrexate may be associated with amelioration of symptoms, reduction in serum biochemical indices of liver disease, and reduction in hepatic inflammation. However, prospective, randomized controlled trials will be necessary for definitive evaluation of the effects of methotrexate on the quality of life and survival of patients with primary biliary cirrhosis.
评估低剂量口服甲氨蝶呤治疗原发性胆汁性肝硬化的疗效。
在一项开放标签试验中，10例有症状的原发性胆汁性肝硬化患者接受了每周15毫克剂量的甲氨蝶呤治疗。
8例患者完成了1年的治疗，6例完成了2年的治疗。所有接受至少1年治疗的患者瘙痒和乏力症状均有所减轻。治疗1年和2年时，血清碱性磷酸酶、谷丙转氨酶和IgM的平均水平均低于相应的基线平均值。3例患者在治疗期间血清总胆红素升高。1例I期疾病患者的血清转氨酶和碱性磷酸酶恢复正常。尽管在1年和2年时肝脏活检显示炎症浸润强度降低，但也显示纤维化增加，提示疾病进展。5例患者停用甲氨蝶呤：4例因疾病进展（1例在4个月时、1例在1年时、2例在2年时），1例因顽固性瘙痒（在4个月时）。所有患者均经历了短暂的粘膜炎和间歇性消化不良。
这些发现表明，甲氨蝶呤治疗原发性胆汁性肝硬化对晚期疾病患者无益；对早期疾病患者，甲氨蝶呤可能与症状改善、肝脏疾病血清生化指标降低及肝脏炎症减轻有关。然而，需要进行前瞻性随机对照试验，以明确评估甲氨蝶呤对原发性胆汁性肝硬化患者生活质量和生存的影响。
