osteoprotegerin and Hepatitis-C--Chronic

Topics: Case-Control Studies; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Osteoprotegerin; Polymorphism, Single Nucleotide; Receptor Activator of Nuclear Factor-kappa B

Noninvasive methods for liver fibrosis evaluation in chronic liver diseases have been recently developed, i.e. transient elastography (Fibroscan™) and blood tests (Fibrometer®, Fibrotest®, and Hepascore®). In this study, we aimed to design a new score in chronic hepatitis C (CHC) by selecting blood markers in a large panel and we compared its diagnostic performance with those of other noninvasive methods.. Sixteen blood tests were performed in 306 untreated CHC patients included in a multicenter prospective study (ANRS HC EP 23 Fibrostar) using METAVIR histological fibrosis stage as reference. The new score was constructed by non linear regression using the most accurate biomarkers.. Five markers (alpha-2-macroglobulin, apolipoprotein-A1, AST, collagen IV and osteoprotegerin) were included in the new function called Coopscore©. Using the Obuchowski Index, Coopscore© shows higher diagnostic performances than for Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™ in CHC. Association between Fibroscan™ and Coopscore© might avoid 68% of liver biopsies for the diagnosis of significant fibrosis.. Coopscore© provides higher accuracy than other noninvasive methods for the diagnosis of liver fibrosis in CHC. The association of Coopscore© with Fibroscan™ increases its predictive value.

Topics: Adult; alpha-Macroglobulins; Apolipoprotein A-I; Aspartate Aminotransferases; Biomarkers; Collagen Type IV; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Osteoprotegerin; Prospective Studies; Research Design; Sensitivity and Specificity; Severity of Illness Index

The failure of the immune response to clear the Hepatitis C virus (HCV) results in chronic inflammation that leads to liver cirrhosis. In general, women have a better prognosis than men and this may be associated with increased levels of anti-inflammatory mediators that are positively regulated by female sex hormones. Our aim was to determine if a cohort of Irish women who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source, had altered levels of circulating cytokine levels compared to women who spontaneously resolved infection, men with HCV infection or age-matched healthy controls. Twenty post-menopausal women and 20 men with chronic HCV infection (genotype 1), 20 post-menopausal women who resolved infection and age and sex-matched controls were recruited for the study. Levels of circulating cytokines were assessed by ELISA. Circulating IL-6, Oncostatin-M, TNF-α, CXCL10, CCL18, VEGF and GM-CSF did not differ between groups. Both men and women with HCV had significantly elevated levels of circulating Osteoprotegerin (OPG). However, male but not female HCV patients had elevated levels of circulating Matrix Metalloprotease-9 (MMP-9). An increased OPG: MMP-9 ratio in the circulation of females compared to males with chronic HCV may help protect against HCV-associated liver disease and explain the slow progress of liver disease in this cohort.

Topics: Aged; Case-Control Studies; Cytokines; Estradiol; Female; Follicle Stimulating Hormone; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Inflammation Mediators; Liver; Male; Matrix Metalloproteinase 9; Middle Aged; Osteoprotegerin; Postmenopause

Osteoprotegerin is decoy receptor for osteoclast activating factor, RANKL, and impairs osteoclast funtion. Since osteoporosis is common in primary biliary cirrhosis (PBC), we investigated osteoprotegerin, RANKL and markers of bone turnover in PBC.. Serum osteoprotegerin, RANKL, osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (CTX-I) were measured by ELISA in 41 patients with PBC, 16 women with chronic hepatitis C (CHC), and as controls in 44 age-matched healthy and 74 post-menopausal osteopenic otherwise healthy women.. Serum osteoprotegerin levels were higher in PBC patients (7.8+/-3.0 pmol/l) than in healthy controls (4.4+/-2.3 pmol/l) and osteopenic women (4.0+/-1.0 pmol/l, P<0.0001 for both). RANKL levels were lower in PBC (0.9+/-1.8 pmol/l, P<0.0001) than in healthy controls (1.3+/-0.5 pmol/l). In CHC both osteoprotegerin (9.7+/-4.2 pmol/l) and RANKL (3.2+/-4.7 pmol/l) were elevated compared to the control groups (P<0.0001, for both). There was a positive correlation between serum osteoprotegerin and OC, CTX-I and AST but not with bone mineral density in PBC.. The mechanisms and role of elevated osteoprotegerin and low RANKL in PBC are unclear, but it might partly represent a compensatory mechanism to negative balance of bone remodeling. High OPG and RANKL levels found in CHC might suggest that inflammatory process in the liver could also contribute to the elevation of osteoprotegerin.

Topics: Adult; Aged; Biomarkers; Bone Density; Bone Remodeling; Carrier Proteins; Female; Femur Neck; Glycoproteins; Hepatitis C, Chronic; Humans; Liver Cirrhosis, Biliary; Lumbar Vertebrae; Membrane Glycoproteins; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor