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Prevalence of hepatitis C virus infection in patients with cardiomyopathy
Vijaya Boyella;1, Ikenna Onyebueke;1, Najabh Farraj;1, Suzette Graham-Hill;1, Cherif El Younis;2, Nora V. Bergasa3,*
1 Kings County Hospital Center
2 Brookdale University Hospital, Brooklyn
3 Department of Medicine, Metropolitan Hospital Center, New York, New York.
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">No conflict of interests exist</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Investigator initiated study supported by Roche Pharmaceuticals&#46;</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0010" class="elsevierStylePara elsevierViewall">Chronic hepatitis C can be associated with extrahepatic manifestations including cryoglobulinemia&#44; lymphoma&#44; thyroiditis&#44; and membranoproliferative glomerulonephritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a>-<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> An association between chronic hepatitis C and cardiomyopathies has also been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a>-<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Myocarditis is an inflammation of the myocardium that can be caused by several cardiotropic viruses and that can lead to dilated cardiomyopathy and heart failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11</span></a>-<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> A high prevalence of hepatitis C virus infection has been reported in patients from Japan with hypertrophic cardiomyopathy&#44; dilated cardiomyopathy and myocarditis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a>-<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14</span></a>-<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Recently&#44; the case of a patient with cardiomyopathy and chronic hepatitis C in whom the treatment of the viral hepatitis had been associated with disappearance of the hepatitis C virus from serum and the resolution of his symptoms of heart failure was reported&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> According&#44; to explore further this association&#44; we studied the prevalence of chronic hepatitis C in a group of patients with dilated cardiomyopathy from the United States&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="p0020" class="elsevierStylePara elsevierViewall">This was a prospective study of patients with ischemic and non-ischemic cardiomyopathy who were being followed at the cardiology clinic of a tertiary public hospital in Central Brooklyn&#46; Cardiomyopathy was defined as an ejection fraction of less than 40&#37; as evaluated by a transthoracic echocardiogram&#46; All the patients signed an informed consent prior to participating in the study&#46; The study period was from December 2006 to March 2007&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Serum samples were sent to a commercial laboratory for determination of hepatitis C antibody by an enzyme linked immunosorbent assay and for quantitation of hepatitis C viral RNA by the COBAS Taqman real time by PCR methodology&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">The study was approved by the Institutional Review Board&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="p0035" class="elsevierStylePara elsevierViewall">Sixty-three patients were recruited&#46; The study group was comprised of 41 patients with non ischemic and 22 patients with ischemic cardiomyopathy&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">The median age was 61&#46;4 years &#40;range 32 to 85&#41; in the patients with ischemic cardiomyopathy&#44; and 51 &#40;range 32 to 85&#41; in the group with non-ischemic cardiomyopathy&#46; There were nineteen women and 23 men in the group of patients with non-ischemic cardiomyopathy&#44; and five women and seventeen men in the group of patients with ischemic cardiomyopathy &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table I</a>&#41;&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0045" class="elsevierStylePara elsevierViewall">The diagnosis of cardiomyopathy had been made by a transthoracic echocardiogram showing findings of muscular dysfunction consistent with the different patterns of cardiomyopathy&#46; The median ejection fraction in the patients with non-ischemic dilated cardiomyopathy was 25&#37; &#40;range 10 to 40&#41;&#59; four patients in this group had features consistent with hypertrophic cardiomyopathy&#46; The median ejection fraction of the group of patients with ischemic cardiomyopathy was 30&#37; &#40;10 to 40&#41;&#46; Thirty nine of the 41 patients with non-ischemic cardiomyopathy had had a cardiac catheterization&#44; which had been normal in all&#46; All the patients with ischemic cardiomyopathy had had an abnormal cardiac catheterization revealing vessel disease &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table II</a>&#41;&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0050" class="elsevierStylePara elsevierViewall">None of the patients had evidence of acute viral hepatitis based on the hepatic profile available at the time of serum collection&#46; Of the 41 patients with non-ischemic cardiomyopathy&#44; two &#40;4&#46;8&#37;&#41; had serum antibodies to the hepatitis C virus and one of those had hepatitis C RNA &#40;2&#46;4&#37;&#41; in serum&#44; consistent with chronic hepatitis C&#46; In the ischemic cardiomyopathy group&#44; one of the 22 patients &#40;4&#46;5&#37;&#41; had serum antibodies to the hepatitis C virus but the hepatitis C RNA was not detected in their serum&#44; consistent with prior infection and resolution of the hepatitis&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="p0055" class="elsevierStylePara elsevierViewall">In this study&#44; the prevalence of chronic hepatitis C&#44; defined by positive hepatitis C virus RNA in serum in patients with ischemic cardiomyopathy was 0&#37;&#44; and in patients with non-ischemic cardiomyopathy it was 2&#46;4&#37;&#46; This prevalence is not much higher than the reported for the US population&#44; not suggesting an association between non-ischemic cardiomyopathy and chronic hepatitis C&#46; This finding is in contrast with the reports from Japan&#44; in which a 16&#37; prevalence of chronic hepatitis C in patients with non-ischemic cardiomyopathy was reported&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">The association between chronic hepatitis C in various types of cardiomyopathy was originally reported in Japan&#44; from where most of the literature in this subject has emerged&#46; A study conducted in Italy reported a prevalence of hepatitis C antibodies in patients with cardiomyopathy to be 3&#46;9&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> which was not significantly different from that of patients without dilated cardiomyopathy&#46; A study from Brazil reported a prevalence of hepatitis C carrier state of 2&#46;9&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> similar to our results&#44; not suggesting an association between the two conditions&#46; A publication that reported a literature review on the publications that had revealed an association between dilated cardiomyopathy and chronic hepatitis C stated that a significant association between dilated cardiomyopathy and hepatitis C virus had been found in only two papers&#44; both from Japan and by the same author&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> On the surface&#44; the data published so far&#44; including our paper&#44; do not support an association between chronic hepatitis C virus infection and dilated cardiomyopathy&#59; however&#44; the patient we reported<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> had such a dramatic response to the treatment of his chronic hepatitis C&#44; which was associated with documented improvement of his ejection fraction and disappearance of symptoms of cardiomyopathy&#44; that the potential for this association cannot be ignored as the option to treat with antiviral therapy exists&#46; An association between hepatitis C and cardiomyopathy was also supported another case report from the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">A limitation of this study is that the only test collected prospectively was the blood sample for antibody and hepatitis C virus RNA determination&#59; all other information was collected retrospectively from the medical records&#46; The review of the data&#44; however&#44; did not suggest that the patients with HCV RNA in serum had acute hepatitis C&#59; thus&#44; it is very likely that the patient who had hepatitis C RNA in serum had chronic hepatitis C&#46;</p><p id="p0070" class="elsevierStylePara elsevierViewall">Dilated and hypertrophic cardiomyopathies in patients with chronic hepatitis C were reported to be more prevalent in subjects who had HLA-DPB1<span class="elsevierStyleSup">&#42;</span>0901 and HLA-DRB1<span class="elsevierStyleSup">&#42;</span>1201&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> A Non-HLA gene locus spanning from the NFKBIL1 to the MICA gene loci within the MHC class III-class I boundary region was also reported to be characteristic in patients with dilated cardiomyopathy associated with chronic hepatitis C&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The majority of the patients studied in our study were black&#44; either from the United States or from the Caribbean Islands&#44; consistent with the population of central Brooklyn&#59; accordingly&#44; it is very likely that the HLA make up of these patients was different from that of the patients from Japan in whom a significant prevalence of chronic hepatitis C has been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0075" class="elsevierStylePara elsevierViewall">Patients with chronic hepatitis C and cardiomyopathy tend to be excluded from the treatment of the hepatitis because the cardiac comorbidities increase their vulnerability to serious consequences from the side effects of the medications &#40;e&#46;g&#46; from the anemia&#41;&#46; On the other hand&#44; if the hepatitis C virus infection is the cause of the cardiomyopathy&#44; treating the hepatitis with antiviral medications offers the opportunity to eliminate the virus&#44; and for the recovery of cardiac function in association with the treatment&#44; as exemplified in a previously reported case&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> As treatment of chronic hepatitis C can deter the progression of liver disease&#44; and it may also treat the cardiomyopathy&#44; which is associated with an increased risk of cardiovascular and all mortality&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> it is important to determine if indeed&#44; cardiomyopathy is one of the extrahepatic manifestations of chronic hepatitis C&#46; Thus&#44; studies that explore this association in different ethnic and racial groups properly powered to detect difference in prevalence are warranted&#46;</p></span></span></span>"
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