Bach N, Thung S N, Schaffner F
Department of Medicine, The Mount Sinai Medical Center of the City University of New York, NY, USA.
Arch Pathol Lab Med. 1998 Apr;122(4):342-5.
Primary biliary cirrhosis is a progressive liver disease that is believed to be autoimmune in nature. Treatment, at best, may slow the progression of the disease, although no therapy has been able to halt its progression. Preliminary data suggest a beneficial effect of methotrexate in the treatment of primary biliary cirrhosis. We evaluated the histologic effect of 2 years of treatment with methotrexate.
Liver biopsies were obtained before methotrexate was started and after 2 years of therapy. Ninety-six paired biopsies from 48 patients with primary biliary cirrhosis were reviewed by a pathologist who was blinded to all clinical history and sequence of the biopsies. Variables examined included stage of the disease, degree of portal fibrosis, portal inflammation and piecemeal necrosis, bile duct injury or loss, bile ductular proliferation, lobular inflammation and necrosis, steatosis, granulomas, cholestasis, and nuclear pleomorphism of hepatocytes.
In most categories, pretreatment and posttreatment biopsies did not reflect a change over the 2-year period of treatment. There was a trend toward progression of the stage of the disease, portal fibrosis, bile duct loss, fat, and pleomorphism over the 2 years and toward regression in piecemeal necrosis, bile duct injury, ductular proliferation, granulomas, and lobular inflammation and necrosis.
After 2 years of treatment with methotrexate, the stage of disease and fibrosis of primary biliary cirrhosis continue to progress, although overall, inflammation and bile duct injury decrease with methotrexate treatment.
原发性胆汁性肝硬化是一种进行性肝病，被认为本质上是自身免疫性的。尽管尚无疗法能够阻止其进展，但治疗充其量可能会减缓疾病的进展。初步数据表明甲氨蝶呤在原发性胆汁性肝硬化治疗中具有有益作用。我们评估了甲氨蝶呤治疗2年的组织学效果。
在开始使用甲氨蝶呤之前以及治疗2年后获取肝脏活检样本。由一位对所有临床病史和活检顺序均不知情的病理学家对48例原发性胆汁性肝硬化患者的96对活检样本进行评估。所检查的变量包括疾病分期、门脉纤维化程度、门脉炎症和桥接坏死、胆管损伤或缺失、小胆管增生、小叶炎症和坏死、脂肪变性、肉芽肿、胆汁淤积以及肝细胞的核多形性。
在大多数类别中，治疗前和治疗后的活检样本在2年治疗期间未显示出变化。在这2年中，疾病分期、门脉纤维化、胆管缺失、脂肪和多形性有进展的趋势，而桥接坏死、胆管损伤、小胆管增生、肉芽肿以及小叶炎症和坏死有消退的趋势。
甲氨蝶呤治疗2年后，原发性胆汁性肝硬化的疾病分期和纤维化仍在进展，尽管总体而言，甲氨蝶呤治疗可使炎症和胆管损伤减轻。
