Diagnostic value of serum markers of fibrosis in chronic liver diseases

AIM: To estimate the diagnostic value (DV) of direct markers of liver fibrosis, such as type IV collagen (C-IV), hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1) in combination with indirect markers of fibrosis, such as alanine aminotransferase (АLT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), platelets, tumor necrosis factor-α (TNF-α) in evaluating liver fibrosis/MATERIAL AND METHODS: Sixty-seven patients with chronic diffuse liver diseases were examined. ALT, AST, γ-GTP, and ALP were determined as indirect indicators of fibrosis. The levels of TIMP-1, HA, C-IV, and TNF-α were estimated by ELISA; the stage of fibrosis was determined by the results of indirect liver ultrasound fibroelastography (FE)/RESULTS: According to the results of FE, the patients were divided into 2 groups: 1) (n=25) F≤2 METAVIR and 2) (n=42) F3-F4. While estimating DV of severe fibrosis stages (F3-F4), the area under the ROC curve (AUC) increased for platelets, HA, and C-IV. DV of ALT, AST declined with the higher degree of fibrosis. The highest ratio of test specificity and sensitivity (TSp and TSen) and AUC were observed for AST and HA. ALT and platelets showed low TSen, and TNF-α and TIMP-1 had no TSp. For evaluation of fibrosis (F4), a HA increase of over 57.7 ng/ml had 92.6% TSen and 67.5% TSp; for a C-IV elevation of above 133.1mkg/l, TSen was 85.2%, TSp was 57.5%; for a TIMP-1 rise from 24.4 ng/ml, TSen was 74.1% and TSp was 62.5%. For the diagnosis of fibrosis (F4) with a HA rise of more than 57.7 ng/ml, DV of a positive test was 65.8 (48.65-80.4; 95% CI) and that of a negative test was 93.1 (76.8-99.2; 95% CI). Thus, the negative rather than positive test results are of great diagnostic value for evaluation of the degree of fibrosis/CONCLUSION: The results of the investigation convincingly suggest that examination of the serum markers of fibrosis allows one to estimate with a high probability its presence and severity in patients with hepatic cirrhosis. The so-called direct markers (substances reflecting the biochemistry and regulation of fibrogenesis) are undoubtedly of great diagnostic value.

liver fibrosis, serum markers of fibrosi