目的：运用代谢组学技术分析乙肝肝硬化患者肝肾阴虚及肝胆湿热两种典型证候（同病异证）的血清差异代谢产物及其代谢通路，探寻虚、实两种典型证候的内在物质基础，以期从代谢水平上为中医证候分类提供客观依据。 方法：对符合纳入标准的111例不同证候的乙肝肝硬化患者（肝胆湿热证40例，肝肾阴虚证41例，隐证(无证可辨）者30例）中医症状及体征进行描述性分析，发现两种不同证型的临床信息分布规律及证候特征；采用气相色谱-飞行时间质谱联用（GC-TOF/MS）技术对乙肝肝硬化患者，以及与之相匹配的60例健康人的血清样本进行检测，经非监督的主成分分析（Principal Components Analysis，PCA）、有监督的偏最小二乘判别分析（Partial Least Square Discriminant Analysis，PLS-DA）及监督的正交偏最小二乘法（Orthogonal Partial Least SquareDiscriminant Analysis，OPLS-DA）分析，找出与乙肝肝硬化疾病本身及其两种典型证候相关的差异性物质；运用MetaboAnalyst 3.0数据库，寻找并解析肝胆湿热及肝肾阴虚虚实两种证候间差异性物质的相关代谢通路。 结果：（1）肝胆湿热证中出现频率较高（50%以上）的症状为小便色黄，口干，口苦，口臭或有异味等。肝肾阴虚证中出现频率较高的症状为口干、腰酸、乏力、腿软等。两证共见症/征为口干、尿黄、易怒、舌红。（2）各组间丙氨酸氨基转移酶（Alanine Aminotransferase, ALT）数值无统计学差异（P>0.05）；与健康组比较，隐证组中白蛋白（Albumin，ALB），肝胆湿热证中总胆红素（Total Bilirubin，TBil）、直接胆红素（Direct Bilirubin，DBil）、谷草转氨酶（Aspartate Transaminase，AST）、碱性磷酸酶（Alkaline Phosphatase，ALP）、谷氨酰转肽酶（Gamma-Glutamyl Transpeptidase，GGT）、总胆汁酸（Total Biliary Acid，TBA）及ALB，肝肾阴虚证TBil、ALP、GGT、TBA、ALB值差异均有统计学意义（P<0.05）；与隐证比较，肝胆湿热证TBil、DBil、AST、ALP、TBA、ALB，肝肾阴虚证TBA、ALB差异有统计学意义（P<0.05）；肝胆湿热证与肝肾阴虚证相比，TBil、DBil差异有统计学意义（P<0.05）。（3）代谢组学检测及代谢通路分析，发现各组之间代谢谱均有良好的区分，并获得各组间的差异性物质。发现肝胆湿热及肝肾阴虚两典型证的共同物质10个，去除疾病（隐证）的信息，则得到两证共同物质6个，涉及的代谢通路为甘氨酸、丝氨酸及苏氨酸代谢和苯丙氨酸代谢；同时，分别获得两证各自特异性的代谢物质各8个，分别涉及亚油酸代谢和甘氨酸、苏氨酸及丝氨酸代谢。 结论：运用代谢组学技术，发现肝胆湿热及肝肾阴虚不同证之间既存在病的共同物质（同病），也存在证的差异物质（异证），从而在代谢层面上为中医证候分类的科学性提供客观依据。
Objective: The serum differential metabolites and metabolic pathways of two typical syndromes of Gan Dan Shi Re Pattern(GDSR)and Gan Shen Yin Xu Pattern(GSYX) in patients with hepatitis B cirrhosis (same disease and different patterns) were analyzed by metabonomics, and the intrinsic material basis of two typical syndromes were explored in order to provide an objective basis for the classification of TCM patterns from the metabolic level. Methods: For 111 patients with hepatitis B cirrhosis in accordance with the inclusion criteria (40 patients with GDSR, 41 with GSYX, 30 Latent Pattern (LP, not-obvious characters)，the descriptive analysis was performed to find out the clinical information distribution and syndrome characteristics of two different syndrome types. Then serum samples from the patients with hepatitis B cirrhosis and 60 healthy persons matched with patients were tested based on gas chromatography time of flight coupled with mass spectrometry technique(GC-TOF/MS) to identify the different substances of diseases and two typical patterns. Furthermore, the related metabolic pathway was founded and analyzed by the MetaboAnalyst3.0 database. Results: (1) In this study, the symptoms of high frequency (50% or more) in GDSR were found to be yellow urine, dry mouth, bitter mouth, bad breath or odor, and so on. The symptoms of higher frequency of GSYX were dry mouth, backache, fatigue, and soft legs, etc. through descriptive analysis. The common symptoms/signs of two patterns were dry mouth, yellow urine, irritability, red tongue. (2) There was no significant difference in alanine aminotransferase (ALT) between the groups (P>0.05). Compared with the healthy group, there were statistically significant differences in ALB, TBIL, DBIL, AST, ALP in LP, TBIL, DBIL, AST, ALP, GGT, TBA and ALB in GDSR, TBIL, ALP, GGT, TBA and ALB in GSYX (P<0.05). Compared with the LP, there were statistically significant differences in TBIL, DBIL, AST, ALP, TBA and ALB in GDSR, TBA and ALB in GSYX. There were significant differences in TBIL and DBIL between GDSR and GSYX (P<0.05). (3) There was a good distinction between each two groups and the different substances were obtained through PCA, PLS-DA, OPLS-DA statistical analysis. A total of 10 common substances were found in the two typical patterns, and the common substances were 6 after the information of the disease (LP) removed, involved in the metabolic pathways of glycine, serine and threonine metabolism and phenylalanine metabolism. In the end, 8 specific metabolites were obtained in GDSR, involved inlinoleic acid metabolism and aslo 8 specific metabolites were got in GSYX, involved inglycine, serine and threonine metabolism. Conclusion: There are not only common substances in the disease (same disease), but different substances in the GDSR and GSYX (different patterns), through metabonomics technology, so as to provide an objective basis for the scientificity of TCM pattern classification at the metabolic level.