Circulating CO3-610, a degradation product of collagen III, closely reflects liver collagen and portal pressure in rats with fibrosis

For this study, 68 Wistar rats were used. Serum CO3-610 was measured by ELISA. Liver fibrosis was quantified by Sirius red staining. Serum hyaluronic acid (HA) was measured with a binding-protein assay. Gene expression of collagens I and III, Mmp2 and Mmp9, and tissue inhibitors of matrix metalloproteinase 1 (Timp1) and 2(Timp2) was quantified by PCR. Hemodynamic measurements were taken in a subgroup of animals. A close direct relationship was found between serum CO3-610 and hepatic collagen content (r = 0.78; P < 0.001), superior to that found for serum HA (r = 0.49; P < 0.05). CO3-610 levels in rats with severe fibrosis (43.5 ± 3.3 ng/mL, P < 0.001) and cirrhosis (60.6 ± 4.3 ng/mL, P < 0.001) were significantly higher than those in control animals (26.6 ± 1.3 ng/mL). Importantly, a highly significant relationship was found between serum CO3-610 and portal hypertension (r = 0.84; P < 0.001). Liver Mmp9 expression increased significantly in fibrotic animals but decreased to control levels in cirrhotic ones.Circulating CO3-610 behaves as a reliable indicator of hepatic remodeling and portal hypertension in experimental fibrosis. This peptide could ultimately be a useful marker for the management of liver disease in patients.Identification of non-invasive biochemical markers of liver fibrosis is a major challenge for scientists and clinicians dealing with hepatic diseases. The degree of liver fibrosis has emerged as the primary determinant in the diagnosis, prognosis and management of patients with chronic liver diseases [1,2]. Furthermore, the probably availability of antifibrotic treatments in the near future 3 emphasizes the necessity of having accurate tools that allow the sequential evaluation of changes in collagen turnover induced by these drugs.Liver biopsy (LB) is the gold standard method for the diagnosis of liver fibrosis, providing a unique source of information on fibrosis and assessment of histology. Even for patients in whom serologic tests point to a s