IJCS | Volume 32, Nº2, May/June 2019

284 Rezende et al. Cardiac disorders in chronic hepatitis C Int J Cardiovasc Sci. 2019;32(3)283-289 Review Article of coronary artery disease (CAD) in these individuals. The presence of CAD, in the aforementioned systematic review, was defined as the onset of one of the following disorders: acute myocardial infarction, unstable angina, stable chronic angina, previous coronary artery bypass grafting, stenosis above 50% in one or more coronary vessels, as observed in coronary angiography, and electrocardiographic pattern compatible with myocardial ischemia. The findings also demonstrated an increased risk of cerebrovascular disease in individuals with hepatitis C. 5 The possible mechanisms involved in an increased risk of coronary atherosclerosis would be related to the increase of oxidative stress, metabolic disorders such as the induction of diabetes mellitus due to the greater resistance to insulin in hepatitis C described by other authors, 6 inflammatory processes and local viral replication, a mechanism that is suggested by the demonstration of the presence of HCV in carotid atherosclerotic plaques. 7 Consistent data from these studies suggesting the association between CAD and HCV reinforce the need for monitoring patients with the virus regarding the risk of developing coronary events, and other cardiovascular risk factors should be closely monitored in this population. Cardiomyopathies Myocarditis Myocarditis is related to several etiologies, such as the action of toxic and biological agents and autoimmune mechanisms (infections). Among the infections, viruses are most commonly involved. Classically, up to 1990, enteroviruses, including Coxsackie, have been described as the main causative agents. More recent studies with viral genome research on endomyocardial biopsy specimens have demonstrated the predominance of parvovirus B19 and Herpes virus 6 as etiological agents of myocarditis, although other viruses have been described, observing regional and temporal epidemiological characteristics. 8 The description of HCV as a cause of myocarditis comes from reports in Asia where hepatitis C is very prevalent and the association betweenmyocardiopathies of unknown etiology and HCV infection suggests that this virus could be implicated in the genesis of cardiac disorders. 9 The resolution of acute infection, myocardial fibrosis and subsequent cardiac remodeling could explain the onset of dilated cardiomyopathy, as described below. Dilated cardiomyopathy Idiopathic dilated cardiomyopathy (DCM) is a myocardial disease characterized by increased internal dimensions of the cardiac chambers and impairment of left ventricular (LV) systolic function without an identified etiology. Genetic mutations responsible for defects in the expression of cytoskeletal proteins from myocytes are often considered to cause this cardiac disorder. Despite the genetic mechanism demonstrated, previous myocarditis was observed in almost half of the cases, mainly of viral etiology, suggesting that the acquired component, influenced by other agents, does play an important role in the pathogenesis of this cardiac condition. 10 Although little reported in Brazil, DCM is responsible for about 25% of the causes of heart failure in developed countries. 10 As previously described in this review, the occurrence of chronic myocarditis, mainly of viral etiology, has been postulated as one of the main hypotheses in the pathogenesis of DCM. Again, enteroviruses are the main agents pointed out in the different publications. 8 Matsumori et al., 9 found 6.3% of HCV infection among 663 individuals with DCM in Japan. 9 These figures were not reproduced in amulticenter study conducted in Italy, which found the presence of HCV-positive serology in 12 of 309 (3.9%) patients with DCM., 11 and in another study conducted in Brazil, which found only one case of HCV infection among 34 patients with DCM evaluated by a university hospital in Bahia. 12 The pathophysiology of DCM as a consequence of myocarditis due to hepatitis C virus could be explained by three mechanisms described below. The first was by direct action of the virus, reinforced by viral replication in the myocytes and by the fact that the HCV core protein could damage the structure of these cells. The second mechanism would be the immune system through the activity of B, T cells and macrophages, where the latter are responsible for greater production of cytokines, of which the tumor necrosis factor alpha (TNF alpha) would play a predominant role, as demonstrated in previous studies that observed increased TNF alpha expression in the plasma and in the myocardial cells of individuals with myocarditis and DCM. TNF would affect ventricular systole by inhibition of calcium currents, reducing the entry of this ion in the myocyte, impairing the excitation-contraction coupling of the cardiac cell. In addition, it also contributes to increased nitric oxide production, inhibiting the beta-adrenergic effect onmuscle contraction, causing a negative inotropic