diagnostic and prognostic significance of circulating and intrahepatic endoglin in liver fibrosis associated HCV infection

Endoglin [CD 105], a transforming growth factor-beta [TGF-beta 1] co-receptor, has been implicated in liver fibrogenesis and carcinogenesis. To determine CD 105 in liver tissue and serum of patients with chronic hepatitis C virus [HCV] infection and to correlate CD 105 expression to stage of fibrosis and serum markers of liver fibrosis; TGF-beta 1 and hyaluronic acid [HA]. Liver biopsies from 42 chronic HCV patients and 20 healthy subjects [donors for liver transplantation] were used for tissue quantification of CD 105 by ELISA and Western blot analysis then correlating findings with tissue TGF-beta 1. Serum CD 105 and HA from patients and control subjects were determined by ELISA. According to the stage of liver fibrosis assessed by Ishak scoring system, patients were classified into 3 groups: Group I: with mild fibrosis [stage 1-2] included 16 patients [11 males, 5 females, mean age 34.5 +/- 7.2 years], Group II: with moderate fibrosis [stage 3-4] included 15 patients [12 males, 3 females, mean age 36.5 +/- 4.1 years] and Group III: with severe fibrosis [stage 5-6] included 11 patients [8 males, 3 females, mean age 41.5 +/- 5.6 years]. Patients with severe fibrosis revealed significantly higher intrahepatic expression of CD 105 and TGF-13 1 than those patients with moderate fibrosis [p<0.05, p<0.001], mild fibrosis [p<0.01, p<0.001] and normal liver [p<0.001, p<0.001]. Serum levels of CDI 05 were 7.9 +/- 1.4 ng/mL, 5.4 +/- 0.54 ng/mL and 3.6 +/- 0.52 ng/mL for patients with severe, moderate and mild fibrosis respectively with a significant difference [p<0.001]. Interestingly, serum CD1O5 showed a positive correlation with severity of fibrosis and serum HA concentrations. At a cut off 3.12 ng/mL, CD 105 gave a sensitivity of 70%, specificity of 89% with area under curve [AUC] of 0.781 for diagnosis of liver fibrosis and at cut off 43.2 ng/mL. HA had a sensitivity of 80%, specificity of 96% and AUC of 0.903. Data from this study provide evidence for a new clinical application of endoglin [CD 105] as a complementary biomarker in diagnosis and prognosis of liver fibrosis as well as a possible therapeutic role of endoglin antagonist in the management of cirrhosis