Colchicine treatment of liver fibrosis.
Colchicine treatment of liver fibrosis.
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发表时间：
2006-03
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通讯作者：
N. Nikolaidis;J. Kountouras;O. Giouleme;V. Tzarou;O. Chatzizisi;K. Patsiaoura;A. Papageorgiou;M. Le
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作者：
N. Nikolaidis;J. Kountouras;O. Giouleme;V. Tzarou;O. Chatzizisi;K. Patsiaoura;A. Papageorgiou;M. Le
背景/目的秋水仙碱具有抗肝纤维化和抗炎的作用，已被提出用于肝病的治疗。然而，临床试验的结果并不一致。本研究的目的是评价秋水仙碱治疗各种原因肝纤维化的疗效。方法38例患者随机分为两组，分别给予秋水仙碱1 mg/d(A组，n=21)和不服用抗纤维化药物(B组，n=17)。治疗持续至少12个月。在入院前和入院12个月后进行肝脏活检。分别于治疗前、治疗后2个月或每4个月检测肝功能、血清Ⅲ型前胶原氨基端肽(PIIINP)水平及外周血T淋巴细胞(PBTLS)CD4/CD8比值。结果治疗12个月后平均白蛋白水平仅A组升高(p<；0.05)。A组治疗12个月后平均血清PIIINP水平无明显变化；7例患者在治疗后24个月随访期间平均血清PIIINP水平下降(p<；0.05)。在基线时，A组的局灶性或桥接性坏死与外周血淋巴细胞的CD4/CD8比率相关(p<；0.05)。在秋水仙碱治疗12个月后，随着这种相关性的消除，平均血清CD4/CD8比值升高(p<；0.05)；两组之间的比较显示，A组在12个月时CD4/CD8比值升高(p<；0.05)。根据Knoell标准，两组的组织学结果在12个月的随访中保持不变。所有患者对该治疗的耐受性良好。结论秋水仙碱长期治疗肝纤维化患者具有抗炎、抗纤维化和免疫调节作用。
BACKGROUND/AIMS Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. The results from clinical trials have however been inconsistent. The aim of the present study was to evaluate the effect of colchicine in the treatment of patients with hepatic fibrosis of various etiologies. METHODOLOGY Thirty-eight patients were randomized to receive either colchicine 1 mg per day (n=21, group A) or no antifibrotic agent (n=17, group B). Treatment lasted for at least 12 months. Liver biopsy was performed prior to entry and after 12 months. Liver function tests, serum aminoterminal peptide of procollagen III (PIIINP) levels and CD4:CD8 ratio of peripheral blood T lymphocytes (PBTLs) were performed at baseline and bimonthly or every 4 months post-treatment. RESULTS Mean albumin serum levels increased 12 months post-treatment period only in group A (p<0.05). Mean serum PIIINP levels did not change significantly after 12 months of treatment in group A; in 7 patients a reduction in mean serum PIIINP levels was noticed during 24-month post-treatment follow-up period (p<0.05). At baseline, a correlation between focal or bridging necrosis and CD4:CD8 ratio of PBTLs was noticed in group A (p < 0.05). The mean serum CD4:CD8 ratio was increased after 12 months of colchicine treatment (p<0.05) associated with abrogation of this correlation; comparison between the two groups revealed increased CD4:CD8 ratio in group A at 12 months (p<0.05). The histological findings according to Knodell criteria in both groups remained unchanged after 12 months follow-up. The treatment was well tolerated in all patients. CONCLUSIONS Long-term colchicine treatment in patients with hepatic fibrosis appears to exert an anti-inflammatory, anti-fibrotic and immunomodulatory effect.