Both Bleomycin molecular weight markers showed an excellent predictive value for advanced

fibrosis, confirming the results of other studies [28–30]. In our study, several other markers failed to show any predictive value for advanced fibrosis. These markers consisted of matrix remodelling indicators such as MMP-1, MMP-2 and YKL-40, as well as several molecules related to regulation of metabolism (leptin, insulin, and NGF) and inflammation (sICAM, sVCAM, sFas, sFasL and MIF). Notably, we found that HGF is a good predictive marker of advanced liver fibrosis. To the best of our knowledge, this is the first study that shows that serum HGF is a good predictive marker of advanced liver fibrosis in patients with chronic hepatitis C. HGF is a factor for paracrine cellular growth, motility and morphogenesis. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial and endothelial cells, but also acts on haemopoietic progenitor cells. It has been shown to have a major role in embryonic organ development, in adult organ regeneration and in wound healing. Serum HGF levels are strongly associated with liver diseases, obesity, IR, and metabolic syndrome [31]. It is possible that elevated HGF levels reflect significant liver

damage or, alternatively, an imbalance between HGF clearance Nintedanib cost and production which could be an indicator of liver dysfunction because the liver is the major organ through which HGF is eliminated from systemic circulation. Many experts believe that current buy Pazopanib noninvasive tests of hepatic fibrosis cannot yet replace liver biopsies [27,32–34]. However, in one prospective study, comparing

liver biopsies with a noninvasive index, it was found that the size of the liver biopsy was inadequate in a significant proportion of patients with chronic hepatitis C. Moreover, when biopsy and marker results were discordant, an explanation could be identified in more than two-thirds of the cases and, in those cases, biopsy failure was more than seven times more common than diagnostic failure of serum markers [35]. Some experts would consider noninvasive serum tests of fibrosis with AUC-ROC areas of 0.85–0.90 to be as good as a liver biopsy for staging fibrosis [36]. The AUC-ROC of HGM-3 for the detection of advanced fibrosis was higher than 90%; a value of accuracy that has not been previously achieved with other markers for HIV/HCV-coinfected patients [30,37,38]. Furthermore, we found that HGM-3 had higher diagnostic accuracy than the HGM-2, APRI, FIB-4 or Forns’ index [15–17,21]. It is important to note that this sample cohort is a subgroup of patients included in a previous report in which we estimated the HGM-2 index [21], and we found that the HGM-3 was more accurate than the HGM-2 index.