唾液咖啡因清除试验检测肝细胞代谢功能正常值范围的研究及应用

Determination of salivary caffeine clearance and establishment of its normal range

目的：建立临床定量检测肝代谢功能的方法及指标。方法：用反相高效液相色谱测定259例正常成人、169例各类肝病患者、15例HBsAg“健康”携带者（HHC）、10例高血脂及12例饮酒者，共465例唾液咖啡因清除率（CL），以定量检测肝代谢功能．结果：正常人CL值呈正态分布（D检验，P＞0．2），故以正态分布法确定正常值。定CL值大于1．37ml／min／kg（－2s）为正常值范围。其诊断肝病的敏感性为85％（143／169），特异性为98％（4／209）．另外可定患者CL值与正常人重叠部分，即1．37～1．86ml／min／kg（－2s～－s）为可疑范围。此外，发现肝病患者CL与肝功能的改变呈明显的伴随关系，但15例HHC、15例脂肪肝、10例高血脂及12例饮酒者肝功能未见异常，而CL值仍低于正常值或在可疑范围内．结论：CL值有早期诊断及预后价值。19例静止期肝硬化（CR）患者，肝功能正常，无明确肝病史，于腹部其他手术时作肝活检而确诊，作CL检测提示CL值能反映肝损害程度的敏感性高于目前常规肝功能试验，有潜在诊断CR的价值。

Objective: To establish the method of quantitative determination of liver metabolic function. Methods: The caffeine (CAF) concentration was measured by RP-HPLC in saliva of 465individuals, including 259 healthy adults, 169 patients with liver diseases, 15 HBsAg healthy carriers (HHC), 10 hyperlipidemics and 12 alcoholics. According to its salivary concentration-time curves, its metabolic clearance (CL) was calculated. Results: The distribution of CL values in healthy subjectS was normal (D-test, P>0.2). A normal range of CL larger than 1.37ml/min/-kg(x-s), could therefore be established according to the method of normal distribution. The sensitivty and specificity for diagnosis of liver diseases were 85%(143/169) and 98%(4/209),respectively. A range of CL=1.37~1.86ml/min/kg(x-2S^x-s) was considered suspicious, because of the overlapping CL values in patients and in healthy subjects. The CL values in 5 of 15 cases of HHC, 6 of 10 cases of hyperlipidemia, and all 12 alcoholics were lower than the normal value. A significant correlation between CL value and change in hepatic metabolic function was also observed in patients with liver disease. The CL values in 15 HHC, 15 fatty liver, 10 hyperlipidemics and 12 alcoholics were also lower than the normal value or fell on the 'suspicious' range, while their hepatic function remained normal. It is suggested that CL value can be one of the indices for early diagnosis and prognosis. Conclusions: In 19 inactive cirrhotic patients without previous history of hepatic disaese or abnormal liver function who were diagnosed by liver biopsy, CL determination could be diagnostic and prognostic. It is more sensitive than the conventional hepatic function tests in detecting liver impairment and may have potential diagnostic significance in liver cirrhosis.