Hepatitis C infection and clearance: associations with atherosclerosis and the metabolic syndrome. (360G-Wellcome-078180_Z_05_Z)

The developing world faces the twin burden of escalating non-communicable disease, particularly cardiovascular disease (CVD) and diabetes, and declining, but still prevalent, infectious disease. A causal link between infection and CVD has been proposed, but evidence for this, and our understanding of its mechanism, is unclear. Egypt has one of the highest rates of hepatitis C worldwide (affecting 40% of adults), and a population which is prone to diabetes and CVD. Whether hepatitis C increases CVD risk is uncertain. Further, conflicting strands of evidence indicate a greater degree of glucose intolerance, but, paradoxically a favourable lipid profile in those with chronic infection, which may reverse on viral clearance. We propose to determine the degree of atherosclerosis (carotid intima media thickness), and the metabolic syndrome (central obesity, glucose, insulin and lipids), in adults with chronic (190), cleared (190) and no infection (190). A substudy of 40 in each group will undergo detailed studies of insulin sensitivity and lipoprotein disturbances, and forearm plethysmography for endothelial function. Findings will inform understanding of the links between infectious and CVD, the mechanisms and impact of the discordant effects of hepatitis C on glucose tolerance and lipid metabolism, and how this relates to atherosclerotic risk.