Evidence For Hcv Involvement In Myocarditis

The literature on HCV involvement in heart disease is not vast and can be divided by results from Japanese and European groups. Matsumori and colleagues160 initially suggested that HCV may play an etiologic role in the development of heart disease. Thirty-six patients with dilated cardiomyopathy were screened for anti-HCV antibodies in serum; 16.7% of the patients and 2.5% of controls (n = 40) were positive. HCV type II RNA was detectable by RT-PCR analysis in 4 of the 6 patients with antibodies against HCV, and RNA was detected in 3 of the positive patients' heart muscle. Matsumori et al.161 then reported finding serologic evidence of HCV infection in 6 of 35 patients with hypertrophic cardiomyopathy versus 2% to 3% of patients with ischemic heart disease; HCV RNA was detected in the heart RNA from 3 of the 6 positive patients who had hypertrophic cardiomyopathy. This was followed by another group's findings that HCV RNA could be detected in the hearts and livers of 3 patients with chronic active myocarditis.162 A multicenter study in Japan published in 1998 had examined 697 patients with hypertrophic cardiomyopathy and 663 patients with dilated cardiomyopathy for the presence of anti-HCV antibodies in sera:163 10% to 11% of the former and 6% of the latter were positive. In normal blood donors 2% to 3% were positive. In another Japanese study, 9 of 65 patients with hypertrophic cardiomyopathy tested positive for anti-HCV antibodies (13%-14%) versus 2% to 3% of the control population;164 HCV RNA was also detected in 5 of the HCV positive patients.

In contrast to these findings of about 10% to 15% HCV positivity in patients with heart disease in Japan, Figulla and colleagues in Germany found a much lower percentage of dilated cardiomyopathy or myocarditis patients (n = 73) with anti-HCV sera: 1%-2% as opposed to 6% in the control group.165 These workers concluded there was little obvious correlation between HCV exposure and heart disease. Another European study found no correlation in the sera or by PCR analysis between HCV or other microorganisms and end-stage idiopathic dilated cardiomyopathy (n = 37); 39 patients with end-stage dilated cardiomyopathy of known etiology were used as controls.166 Prati and colleagues167 studied HCV involvement in 752 patients with dilated cardiomyopathy and other heart diseases (along with 443 control samples) and found a lower percentage of anti-HCV antibodies in sera from heart patients (3% to 4%) than in the control group (6% to 7%), concluding that HCV exposure did not correlate with myocarditis or dilated cardiomyopathy. A study in Greece also found no evidence for linkage between HCV infection and dilated cardiomyopathy.168 Patients with chronic HCV infection (n = 102) and dilated cardiomyopathy (n = 55) were assayed for exposure to HCV serologically and by RT-PCR. No chronic HCV patients had evidence of dilated cardiomyopathy, and no dilated cardiomyopathy patients showed serologic or molecular evidence of HCV infection.

The possible etiologic role of HCV infection in the development of myocarditis is still debatable: the reasons for the disparity in results between the Japanese and European studies are not evident. A difference in viral strains that circulate locally may represent a key factor.169 HCV is a long-term persistent infection, permitting quasispecies variations to occur170,171 and be selected within the unique environment of any human; such viral quasispecies might not be dominant in a general viral population.172 This has been well-documented in HIV-infected patients. Individual variations or those endemic in a population as a locally dominant quasispecies can be postulated to influence disease outcome in those infected.173 Therefore, it might be illuminating to determine whether significant differences in HCV sequences exist between those strains isolated from diseased heart tissues in Japan and those from HCV strains circulating generally in Japan and in Europe.

The problematic correlation of HCV infection with heart disease might also be said to exist for enteroviral infections and myocarditis, although the weight of the cumulative evidence makes for an extremely strong inferential argument for enterovirus causation of human myocarditis despite some reports in which enteroviral RNA has not been detected in diseased hearts. However, a similar weight of evidence does not exist at present supporting the role of HCV as a key agent of myocarditis. One primary aspect of the argument for enteroviral, specifically CVB, involvement in heart disease derives from correlative animal studies; it is clear that human CVB can cause acute myocarditis in mice and that this is both virus strain (eg, reference 84) and mouse strain174 dependent. As for Ad involvement in heart disease, there is no current murine model as easily used for HCV heart disease as that available for the CVB, but this may be changing. A report offers a murine model of flavivirus infection,175 thus raising the possibility of eventually deriving a murine model for flavivirus-induced myocarditis. Use of a transgenic mouse model176 to model anti-HCV protection using vaccinia virus-HCV chimeric vaccines has also been reported. GB virus-B is a member of the flavivirus family and is closely related to HCV. Bukh and colleagues177 have shown that GBV-B can replicate in tamarins and induce hepatitis, demonstrating a potential small primate model for HCV infection that might be adapted to heart disease.

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