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Cardiovascular diseases as major extrahepatic manifestations of hepatitis C virus infection: Leukocytes, not hepatocytes, are the targets of hepatitis C virus infection

Akira Matsumori

Almost all viruses cause cardiovascular diseases, and coxsackievirus and influenza virus are thought to be the most common causes of acute myocardial injuries. On the other hand, Hepatitis C Virus (HCV) usually causes chronic myocardial damage. HCV is the cause of many different forms of heart disease worldwide, but few cardiologists are aware of its etiology in heart disease or how to treat it. HCV causes heart failure with both reduced and preserved ejection fraction, such as myocarditis, dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. HCV also causes various arrhythmias, conduction disturbances, and QT prolongation. Cardiac troponins, N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), and immunoglobulin free light chains are good biomarkers of cardiovascular diseases in HCV-positive patients. It is known that atherosclerosis is an inflammatory process, and HCV infection may be an important risk factor for atherosclerosis.

We found that HCV infects mononuclear cells, and that the target of HCV infection is mononuclear cells, not hepatocytes. Infected monocytes and macrophages cause chronic persistent inflammation, and this inflammatory reaction can cause various types of organ damage as well as myocyte necrosis, fibrosis, and myocyte hypertrophy in the heart. The diverse clinical biology of HCV and the presence of multiple extrahepatic disease syndromes can be explained by the effect of HCV-infected mononuclear cells in the bone marrow and the viral modulation of host immune responses. It was suggested that CD68 monocytes/macrophages are the major targets of HCV, and pharmacologic preparations targeting leukocyte infection can be used to treat HCV. New therapeutic trials of HCV infections including cardiovascular diseases will be needed based on the new hypothesis that the target of HCV infection is mononuclear cells. In addition to anti-HCV agents, cytapheresis and anti-inflammatory therapy by anti-histaminic agents and pycnogenol show promise. The aim of this review is to evaluate the evidence that HCV causes various cardiovascular diseases, and discuss on the pathogenesis of these disorders.