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In a typical early study, Yamada et al. evaluated the diagnostic significance of fibrosis stage determination with 36 patients having hemophilia and chronic hepatitis C (average age 31±9), using serum content of PIII P, IV-C and HA as liver fibrosis indicators. The obtained results were compared with the conclusions obtained by means of liver biopsy. As a result, a considerable correlation was observed between fibrosis stage 3-4 and HA, but not the serum content of PIIIP and IV-C. All patients received standard interferon therapy, the levels of the studied markers were evaluated 6 months after the therapy cessation. The patients with a stable response had a positively reduced content of all three serum markers compared to non-responders Thus, the HA marker can be used to diagnose stages 3 and 4 of the fibrogenesis, as well the evaluation of the therapy effect. PIIIP, as a marker of active fibrosis generation, reflected the intensity of the inflammation and fibrogenesis rather than the fibrosis intensity [70], Considerable correlation of the extracellular matrix markers with the degree of fibrosis intensity were reported in other studies [21, 40, 65]. High diagnostic role of the concentration of HA, MMP, TIMP, PIIIP, and IV-C for the differentiation of stage 1 and 2 fibrosis from stage 3 and 4 fibrosis was demonstrated by Murawaki Y et al. [68]. The research by Shimizu I [21] demonstrated that the level of P III P and IV-C correlated with iron concentration in the liver. Receiver operating characteristic (ROC) curves were built to find out the relationship between serum level of hyaluronic acid (HA), type III procollagen (PCIII), Nterminal procollagen III peptide (PIIINP), laminin (LN), typeIV collagen (C-IV) analysed for by radioimmunoassay, and hepatic fibrosis (114 chronic hepatitis patients) [69]. The sensitivity of HA plus PIIINP was 55.1 %, it was the most sensitive combination. Combined three or more than three indices that based on HA, the specificity was 100 % [69]. However, only PIIINP and PCIII had significant difference between G1 and G2 (PIIINP: 13.16+/-8.07 vs 8.32+/-5.09; PCIII: 164.22+/-65.69 vs 138.23+/-77.63) [69]. TIMP content was specified as positively increasing at early stages of fibrosis, while the content of PIIIP is positively increased at the stage of septal fibrosis [40]. PIIIP was in considerable correlation with the necro-inflammatory processes in the liver and reflected more the degree of inflammation than the stage of fibrosis [70, 71]. TIMP was suggested for differential diagnostics of steatosis and fibrosis of the alcohol-affected liver [72].