Mitchison H C, Bassendine M F, Malcolm A J, Watson A J, Record C O, James O F
Department of Medicine, University of Newcastle Upon Tyne, United Kingdom.
Hepatology. 1989 Oct;10(4):420-9. doi: 10.1002/hep.1840100405.
A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.
开展了一项关于泼尼松龙治疗原发性胆汁性肝硬化的随机、双盲、为期1年的试点研究。19例患者最初每天服用30毫克泼尼松龙，维持剂量为每天10毫克。17例患者接受安慰剂治疗。两组在年龄、绝经状态、肝脏组织学分期和胆红素方面相匹配。治疗耐受性良好，无患者退出。两名接受泼尼松龙治疗的患者患糖尿病，一名患十二指肠溃疡，一名患抑郁症。一名接受安慰剂治疗的患者在3个月后死于肝功能衰竭。泼尼松龙治疗后胆汁淤积症状（瘙痒和疲劳）有所改善。泼尼松龙组与安慰剂组相比，转氨酶（p = 0.0214）、碱性磷酸酶（p = 0.0032）、Ⅲ型前胶原肽（p = 0.0103）、免疫球蛋白G（p = 0.0012）和肝脏组织学（p = 0.016）有显著改善；这些变化在非肝硬化患者中最为明显。没有患者出现骨骼症状。57%的患者在治疗前三油酸甘油酯呼气试验异常，65%的患者钙吸收试验异常低。与安慰剂组相比，治疗组在2周时钙吸收显著增加（p < 0.02），但在1年时未增加。1年后，泼尼松龙组的股骨光子吸收测定值下降（-3.5%，而安慰剂组为+0.5%，p < 0.05），连续骨活检的小梁骨体积（-6%，而安慰剂组为-2.8%，p < 0.005）和吸收表面（-11%，而安慰剂组为+2%，p < 0.02）也下降。泼尼松龙似乎对原发性胆汁性肝硬化有良好的肝脏作用，但代价是骨丢失增加至预期速率的两倍左右。泼尼松龙治疗在原发性胆汁性肝硬化中值得进行更长时间的进一步评估，要注意选择最可能受益的患者，并持续观察骨量，以更好地确定“成本/效益”比。
