原发性胆汁性肝硬化PBC资料.pptVIP

病理组化： PBC病人的胆汁郁积 （ × 1600） 病理组化： 四期PBC病人的肝硬化改变 （×125） 诊断及鉴别诊断 ALT?, rGT ?： US, CT, MRI(－) AMA/AMA-M2 +，OR histology AMA/AMA-M2 +，with normal biochemistry and histology- followup! PBC: Diagnosis PBC: Differential diagnosis PBC female +++ pruritus+++ ALT/ASL AKP/rGT AMA-M2 ERCP－ Sjogren AIH young and middle age femle pruritus+ ALT/AST AKP/rGT ANA/SMA/LKM1/SLA ERCP － SLE/RA PSC male++ pruritus++ ALT/ASL AKP/rGT ANCA ERCP＋ UC 治 疗 PBC: therapeutic agents 药物(medicine) 皮质激素（corticosteroids) 硫唑嘌呤(azothioprine) 环孢素(cyclosporine A) D-青霉胺（penicillamine) 甲氨喋呤(Methotrexate) 秋水仙素 (cochicine) 马洛替脂 （malotilate) 沙利度胺（Thalidomide） 熊去氧胆酸(UDCA) efficacy probale minimal no no in trial minimal no no definite side effect ＋ ? ＋＋ ＋＋ ＋ 0 0 ＋＋ 0 Ursodeoxycholic Acid UDCA The goal of UDCA in PBC 症状改善( relieving symptoms) 生化指标改善(improving biochemical tests) 组织学改善( halting histological progression) 生存改善( improving survival) 肝移植的需求减少( decreasing the need of OLT) Beuers U, et al. Hepatology 1998; 28: Promote bile secretion ?Ca++ influx, PKC, MAPK：Erk-1, 2 Anti-apoptosis oppose cytotoxicity of hydrophobic bile acids Immune regulation ? inhibit HLA-I, II expression in hepatocytes, bile duct epithelium inhibit production of IL-2, IL-4, IFNg byPBMC corticosteriod-like action? UDCA: mechanism of action Beuers U, et al. Hepatology 1998; 28 Gastroenterol and Hepatol 1998; 13:659-64. UDCA improves survial of PBC patients Poupan RE, et al. N Engl J Med 1994; 330:1332-7. UDCA Prolongs OLT-free Survival in PBC Patients Probability of survival % Poupan RE, et al. Gastroenterology 1997; 113:884 PBC- 10 year’s UDCA Poupan RE, et al. Hepatology 1999;29;1668-71. PBC:symptomatic treatment 瘙痒(pruritus) 胆酪胺(choletyramine) 4g早餐前后（～16g/d) 利福平(rifampicin) 150 mg, bid 其它试验性药物那络酮(naloxone)、那曲酮(naltrexone) 肝移植(Orthotopic Liver Transplantation, OLT) 骨质疏松(osteopenia) Ca 1.5g /d, Vit D 1000 IU/d (绝经后妇女? HRT) 二膦酸盐(biphosphonates) 脂溶性维生素( fat soluble vitamins)