Neuman Manuela G, Cameron Ross G, Haber Julia A, Katz Gady G, Blendis Laurence M
Division of Clinical Pharmacology, Sunnybrook and Women's Health Sciences Centre, Toronto, Ontario, Canada.
Liver. 2002 Jun;22(3):235-44. doi: 10.1046/j.0106-9543.2002.01640.x.
BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease that results in cholestasis and bile duct loss. Ursodeoxycholic acid (UDCA) has been shown to reduce hepatocellular damage in PBC. The study attempted to quantify perisinusoidal collagenization and the number of apoptotic bodies in PBC liver biopsies from patients in a randomized control trial treated with UDCA compared to those who received placebo.
Twenty-eight patients with PBC (10 cirrhotic, 18 non-cirrhotic; 13 treated with UDCA, 15 treated with placebo) were compared with 32 controls with normal hepatic histology on light microscopy. Liver biopsies were examined for degree of perisinusoidal fibrosis and apoptotic activity using electron microscopy.
The degree of perisinusoidal fibrosis and apoptotic activity was similar in pretreatment biopsies of UDCA and placebo-treated patients. After two years of placebo, patients showed a significant increase in fibrosis (P < 0.001). In contrast, there were no changes in non-cirrhotic and a decrease in fibrosis in cirrhotic patients given UDCA. At baseline, PBC patients had higher numbers (apoptotic cells/100 hepatocytes +/- SE) of apoptotic cells (7 +/- 3), than controls (2 +/- 0.5) (P < 0.05), with no difference between cirrhotic and non-cirrhotic patients in the two groups of patients. After two years, the numbers of apoptotic cells in UDCA-treated patients decreased significantly compared to baseline (3 +/- 2) (P < 0.05); with placebo patients the number of apoptotic cells increased (12 +/- 5) (P < 0.05).
Treatment with UDCA prevents the deposition of perisinusoidal collagen and reduces the apoptotic activity in PBC patients after 2 years of therapy.
背景/目的：原发性胆汁性肝硬化（PBC）是一种导致胆汁淤积和胆管丧失的慢性肝病。熊去氧胆酸（UDCA）已被证明可减少PBC患者的肝细胞损伤。本研究试图在一项随机对照试验中，对接受UDCA治疗的PBC患者与接受安慰剂治疗的患者的肝活检组织中窦周胶原化程度和凋亡小体数量进行量化比较。
将28例PBC患者（10例肝硬化患者，18例非肝硬化患者；13例接受UDCA治疗，15例接受安慰剂治疗）与32例肝组织学正常的对照者进行光镜检查比较。采用电子显微镜检查肝活检组织的窦周纤维化程度和凋亡活性。
UDCA治疗组和安慰剂治疗组患者治疗前活检组织的窦周纤维化程度和凋亡活性相似。接受安慰剂治疗两年后，患者纤维化程度显著增加（P < 0.001）。相比之下，接受UDCA治疗的非肝硬化患者纤维化无变化，肝硬化患者纤维化程度降低。基线时，PBC患者的凋亡细胞数量（凋亡细胞/100个肝细胞±标准误）（7±3）高于对照组（2±0.5）（P < 0.05），两组患者中肝硬化和非肝硬化患者之间无差异。两年后，与基线相比，UDCA治疗组患者的凋亡细胞数量显著减少（3±2）（P < 0.05）；安慰剂治疗组患者的凋亡细胞数量增加（12±5）（P < 0.05）。
UDCA治疗可预防窦周胶原沉积，并在治疗2年后降低PBC患者的凋亡活性。
