McCormick W C, Bell C C, Swell L, Vlahcevic Z R
Gut. 1973 Nov;14(11):895-902. doi: 10.1136/gut.14.11.895.
Bile acid pool size and kinetics were determined in 17 patients with cirrhosis and 11 patients without liver disease and correlated with the severity of liver disease as determined by the usual clinical and laboratory criteria. In order to assess the severity of liver disease, a grading system was devised which assigned numerical values to various clinical signs and laboratory results. The total clinical score and the patients were divided into two groups of advanced (7-18 points) or mild (1-6 points) cirrhosis. The clinical rating was then correlated with the various aspects of bile acid metabolism. Cholic acid synthesis was markedly reduced in the early stages of cirrhosis and continued to decrease with the advancement of the liver disease. There was an inverse correlation between synthesis of cholic acid and the severity of cirrhosis. Nine of the 10 patients with advanced cirrhosis and a very low cholic acid synthetic rate (average 68 mg per day) died within one to 13 months from the start of the study. Patients with mild cirrhosis also had significantly reduced cholic acid synthesis (average 152 mg per day) but they all were well and alive three to 23 months after the study. In contrast, chenodeoxycholic acid synthesis was not markedly affected in either patients with mild or advanced cirrhosis. There was also a high degree of correlation between the fractional daily turnover rate of cholic acid and the severity of liver disease. The fractional daily turnover rate of cholic acid was greatly reduced (50%) in patients with advanced cirrhosis. Deoxycholic acid was reduced in patients with mild cirrhosis and virtually absent from the bile of patients with advanced cirrhosis. The findings of the present report provide evidence that cholic acid synthesis is a sensitive indicator of the hepatocellular damage, whereas chenodeoxycholic acid synthesis is relatively unaffected by cirrhosis. The selective alteration in cholic acid synthesis probably resides in a deficiency of one or more enzymes regulating the formation of the 3-keto, 7 alpha, 12 alpha-dihydroxy precursor of cholic acid.
对17例肝硬化患者和11例无肝脏疾病的患者测定了胆汁酸池大小和动力学，并将其与根据常规临床和实验室标准确定的肝脏疾病严重程度相关联。为了评估肝脏疾病的严重程度，设计了一种分级系统，该系统为各种临床体征和实验室结果赋予数值。根据总临床评分，将患者分为晚期（7 - 18分）或轻度（1 - 6分）肝硬化两组。然后将临床分级与胆汁酸代谢的各个方面相关联。在肝硬化早期，胆酸合成明显减少，并随着肝脏疾病的进展持续下降。胆酸合成与肝硬化严重程度呈负相关。10例晚期肝硬化且胆酸合成率极低（平均每天68毫克）的患者中，有9例在研究开始后的1至13个月内死亡。轻度肝硬化患者的胆酸合成也显著减少（平均每天152毫克），但他们在研究后的3至23个月内均状况良好且存活。相比之下，轻度或晚期肝硬化患者的鹅去氧胆酸合成均未受到明显影响。胆酸的每日分数周转率与肝脏疾病严重程度之间也存在高度相关性。晚期肝硬化患者的胆酸每日分数周转率大幅降低（50%）。轻度肝硬化患者的脱氧胆酸减少，晚期肝硬化患者的胆汁中几乎不存在脱氧胆酸。本报告的研究结果表明，胆酸合成是肝细胞损伤的敏感指标，而鹅去氧胆酸合成相对不受肝硬化影响。胆酸合成的选择性改变可能在于调节胆酸3 - 酮、7α、12α - 二羟基前体形成的一种或多种酶的缺乏。
