ObjectiveTo investigate the value of the four serum liver fibrosis markers, i.e., procollagen Ⅲ (PCⅢ), type Ⅳ collagen (C-Ⅳ), hyaluronic acid (HA), and laminin (LN), in the diagnosis of liver fibrosis. MethodsA retrospective analysis was performed for the clinical data of 155 patients with liver cirrhosis, 42 patients with liver cirrhosis and primary hepatic carcinoma (PHC), and 150 patients with chronic hepatitis who were admitted to The First Affiliated Hospital of Southwest Medical University from April 2018 to April 2019, and 73 healthy individuals who underwent physical examination were also enrolled. The serum levels of the above four markers were measured for all subjects and were compared between groups. The receiver operating characteristic (ROC) curve was plotted to compare the diagnostic efficiency of these four markers. The t-test was used for normally distributed continuous data between two groups; the Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. ResultsThe patients with liver cirrhosis and the patients with liver cirrhosis and PHC had significantly higher serum levels and positive rates of the four markers than the patients with chronic hepatitis and the healthy subjects (all P＜0.05). while there were no significant differences in the levels and positive rates of PCⅢ, C-Ⅳ, and HA between the patients with liver cirrhosis and the patients with liver cirrhosis and PHC (all P＞0.05). Although the patients with liver cirrhosis and PHC had a significantly higher serum level of LN than those with liver cirrhosis (P＜0.05), there was no significant difference in the positive rate of LN between the two groups (P＞0.05). The patients with alcoholic cirrhosis had significantly higher serum levels of PCⅢ and C-Ⅳ than those with viral cirrhosis, viral-alcoholic cirrhosis, or autoimmune cirrhosis (all P＜0.05), the patients with autoimmune cirrhosis, alcoholic cirrhosis, or viral-alcoholic cirrhosis had a significantly higher serum level of HA than those with viral cirrhosis (all P＜0.05), and the patients with viral-alcoholic cirrhosis, viral cirrhosis, or alcoholic cirrhosis had a significantly higher serum level of LN than those autoimmune(all P＜0.05). The patients with chronic hepatitis of different etiologies had significantly lower serum levels and positive rates of these four markers than those with liver cirrhosis (all P＜0.05), and the patients with severe viral hepatitis had significantly higher positive rates of the four markers than the other patients (all P＜0.05). PCⅢ, C-IV, HA, LN, and the combination of these four markers had an area under the ROC curve of 0.836, 0.832, 0895, 0.808, and 0.901, respectively, in the diagnosis of liver cirrhosis. HA had a significantly larger area under the ROC curve than PCⅢ, C-Ⅳ, and LN (all P＜0.05), while there was no significant difference between HA and the combination of these four markers (P＞0.05). ConclusionHA has a high diagnostic efficiency in liver fibrosis.