Background Liver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis.Methods Serum specimens were collected prospectively from normal control subjects (n=22) and patients with alcoholic cirrhosis (n=18) or HBV-induced cirrhosis (n=19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)Rime-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA).Results Significant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered commonbiomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis.Conclusions There are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis.Metabonomics is a top-down systems biology tool for conducting research on clinical problems.