|Year : 2014 | Volume
| Issue : 2 | Page : 103-107
Cardiovascular manifestations of hepatitis C virus infection
Pukhrambam Vedanti Devi, Linda Marangmei, Dhanaraj Singh Chongtham, Ratan Ram
Department of Medicine, Regional Institute of Medical Sciences (RIMS), Imphal, India
|Date of Web Publication||18-Sep-2014|
Dr. Linda Marangmei
Department of Medicine, Regional Institute of Medical Sciences (RIMS), Imphal
Source of Support: None, Conflict of Interest: None
Introduction: Hepatitis C virus infection is a major global health problem being the second most common chronic virus infection. It is associated with numerous extra hepatic manifestations of which cardiovascular diseases constitute an important but under diagnosed aspect of the infection. Aim: This study was carried out to evaluate the association between cardiovascular manifestation and HCV seropositivity patients attending Regional Institute of Medical Sciences (RIMS) in Imphal, Manipur. Materials and Methods: From august 2009 to july 2011, 50 HCV seropositive patients in the department of Medicine, Regional Institute of Medical Sciences, Imphal were evaluated. They were subjected to thorough physical examination and baseline laboratory investigations. Above that, echocardiogram was done for each patient. For statistical analysis of data, statistical package for the social sciences (SPSS16.0 version) and student's t-test was used. Results: In this study, the average age of patients was 44 years, ratio of males to females was 3.5: 1. HCV infection is more common in males who are in the sexually active and married age group 30 to 49 years. In the laboratory parameters high serum glutamic pyruvic transaminase (SGPT) and high erythrocyte sedimentation rate (ESR) were significant indicators of cardiac chamber (left atrial and left ventricular) enlargement and left ventricular diastolic dysfunction in HCV seropositive patients. Conclusion: The result corroborated favorably that the more progressed is the inflammation and liver dysfunction due to HCV infection, the more likely to have cardiovascular changes of cardiac chamber enlargement and left ventricular diastolic dysfunction.
Keywords: Cardiovascular manifestations, Hepatitis c virus infection, Extra hepatic manifestations
|How to cite this article:|
Devi PV, Marangmei L, Chongtham DS, Ram R. Cardiovascular manifestations of hepatitis C virus infection. J Med Soc 2014;28:103-7
| Introduction|| |
Hepatitis C virus (HCV) infection is a global health problem. It is the second most common chronic viral infection in the world with a global prevalence of about 3% (170 million people).  The prevalence rate is higher in persons aged 30-49 years than in older or younger persons, and is higher in males than in females 2.5% versus 1.2% and among certain ethnic groups such as African Americans and Mexican Americans than whites. 
About 3 to 4 million persons are newly infected each year and 80% of the newly infected patients progress to develop chronic infection. A majority of patients are asymptomatic and anicteric. Only 25-40% of the patients develop malaise, weakness and anorexia and some become icteric. Anti HCV can be detected in 50-70% of the patients at the onset of disease symptoms and in approximately 90% of patients 3 months after the onset of infection. HCV is self limited in only 15% of the patients. 
HCV infection has been associated with numerous extra-hepatic manifestations. , They are lichen planus, oral cancer, porphyria cutaneatarda, membranoglomerulonepritis, etc. In addition, auto immune diseases like autoimmune thyroiditis and mixed cryoglobulinemia are also found. Although HCV is primarily a hepatotropic virus, has tropism for other tissues besides the liver. It has been isolated from the myocardium of patients with myocarditis and cardiomyopathy hence, its inclusion among the cardiotropic viruses.  An association between aortic atherosclerosis and HCV infection has been recently suggested. , So are the associations between HCV infection and hypertrophic cardiomyopathy and dilated cardiomyopathy. 
| Materials and Methods|| |
This study was conducted at Regional Institute of Medical sciences, Imphal Manipur. A total of 50 patients of HCV infection who were attending OPD or admitted in the Medicine ward over a period of 24 months extending from August 2009 to July 2011 were enrolled. Patients who were positive for Hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV), those who were below 13 years, patients who were previously diagnosed or with documented cardiac diseases in whom an alternative cause had been identified were excluded from the study.
All selected patients underwent a detailed historical and clinical evaluation. They were subjected to laboratory investigations such as complete hemogram, random blood sugar and liver function test. Above that chest roentgenogram, electrocardiography and echocardiogram were also done. The present study used two dimensional transthoracic echocardiographic imaging to assess for cardiac chamber enlargement and detect pericardial effusion. A definitive diagnosis of HCV infection was based on positive hepatitis C virus antibody in the serum using the enzyme immunoassay test (TRIDOT). For statistical analysis of data, statistical package for social sciences (SPSS 16.0 version) was used. The student's t-test for equality of means was used for comparison of data during analysis. P < 0.05 (5% level of significance) is considered statistically significant.
| Results|| |
Among the 50 patients enrolled in this study, the majority 78% were males while females were 22% showing male predominant affect similar to other reports. The ages of the patients ranged from 22 years to 70 years with a mean age of 44 years. The presenting complaints are depicted in [Figure 1]. General physical findings are shown in [Figure 2] and clinical findings are shown in [Figure 3]. The clinical findings of cardiomegaly were further supplemented from echocardiogram. Echocardiographic findings in HCV seropositive patients are shown in [Table 1].
|Figure 1: Bar chart showing the presenting complaints of patients in study population|
Click here to view
From the [Table 1], it is seen that 12% patients had pericardial effusion of which 10% patients were males and only 2% were females. 40% patients had dilated left atrium (Left Atrium >40 mm). 8% patients had dilated left ventricle (Left ventricle >57 mm).14% patients had dilated right ventricle (Right ventricle >20 mm). None of the patients had biventricular dilatation. Out of the 50 patients, only 8% patients had left ventricular systolic dysfunction (LVEF <45%). 34% patients had LV diastolic dysfunction (E = A/E < A). However, only 4% patients had both LV systolic and diastolic dysfunction. Regarding cardiomyopathy, it is seen that only 4% patients had dilated cardiomyopathy (LVFF < 45% and LV >57 mm) of which one patient was male and the other was female. Also, only one male patient was found to have hypertrophic cardiomyopathy (IVSD/LVPWD >1.5). This patient also had LV diastolic dysfunction and pericardial effusion.
To find any correlation with chamber enlargement and HCV infection, amongst patients with left atrium dilatation, the following laboratory parameters depicted in [Table 2] were studied for statistical significance using the student's t-test for equality of means.
|Table 2: Relation between dilated LA (LA diameter >20 mm) and some parameters|
Click here to view
It is seen that there is statistical significant difference (P < 0.05) with regard to SGPT, hemoglobin, ESR, serum creatinine and random blood sugar (RBS) readings. Though statistically significant difference existed in the readings of hemoglobin, serum creatinine and RBS amongst the HCV seropositive patients with dilated left atrium, majority of them had normal mean values for these parameters. Thus, it was concluded that HCV seropositive patients with dilated left atrium tend to be less anaemic without much kidney dysfunction or hyperglycemia. As majority had a higher mean values for SGPT and ESR which were statistically significant (P < 0.05) it can be deduced that HCV seropositive patients with dilated left atrium tend to have higher readings of serum glutamic oxaloacetic transaminase (SGOT) and ESR. Thus, this observation also shows that the more progressed is the inflammation and liver dysfunction due to HCV infection, the more it is likely to have left atrium enlargement. SGPT and ESR may therefore be good indicators of left atrium dilatation in HCV serpositive patients. Further analysis was done on these 20 HCV seropositive patients with left ventricular diastolic dysfunction. The means of the left ventricular end diastolic diameter (LVEDD) on echocardiography ofthe patients falling into the different laboratory parameter groups as shown in [Table 2] are compared using the student's t-test for equality of means. It is seen from [Table 2] that there is no statistical significant difference (P > 0.05) in the means of LVEDD amongst the patients falling into the different laboratory parameter except those having different SGPT levels. There is a significant difference in the means of LVEDD between left ventricular diastolic dysfunction patients with normal SGPT level and those with high SGPT level. Thus, in HCV infection left ventricular diastolic dysfunction patients with high SGPT levels tend to have larger dimension of the left ventricle when compared to those with normal SGPT levels.
| Discussion|| |
HCVinfection has been associated with numerous extrahepatic manifestations of which cardiovascular diseases like coronary artery disease, myocarditis, dilated and hypertrophic cardiomyopathies have been implicated.  It seems that the development of HCV associated cardiomyopathy may take place in genetically susceptible individuals in whom viral, immunologic and apoptic mechanisms may act in concert to produce myocardial damage.  In HCV heart disease, most patients develop chronic inflammation of the myocardium and later dilated cardiomyopathy attributable to necrosis and loss of myocytes. However, because myocytes do not replicate, proliferative stimuli induced by HCV infection may promote myocyte hypertrophy and hypertrophic cardiomyopathy. 
As per laboratory findings, the mean values of the parameters of liver function test (LFT) and ESR were found to exceed that of the normal range. A combination of factors including cytokine levels, increased inflammation markers (such as low albumin, high globulin, high ESR, etc), thrombosis, endothelial dysfunction, behavioral and social risk factors like alcohol abuse, smoking, malnutrition and liver problems are likely to be the reasons why patients with hepatitis C have an increased risk of cardiovascular disease. , In the present study, 38% patients had abnormal functions of the liver with chronic inflammation. The role of liver enzymes in the assessment of chronic hepatitis C remains important due to the fact that the majority of clinical indexes estimating the disease progression and the degree of liver fibrosis are based in liver transaminases. The serum of patients with HCV infectionhas been shown to have higher levels of SGPT and SGOT than the uninfected persons. , In the present study, similar results were obtained. 92% patients had SGOT >38 IU/L of which 70% were males and 22% were females. 68% patients had SGPT >41 IU/L of which 54% were males and 14% were females. Thus males with HCV seroposivity were strongly associated with elevated SGOT and SGPT levels as has also been previously reported.  Previously, it has been reported that individuals infected with HCV had fewer traditional risk factors for heart disease and stroke than the uninfected patients. They were less likely to have high blood pressure and diabetes.  In the present study, also it was seen that majority of the HCV patients had a lower prevalence of hypertension and elevated blood sugar with only 6% patients having high values for both random blood sugar and blood pressure. In the present study, 11 patients had abnormal position of the apex beat suggestive of ventricular enlargement. 7 patients had left ventricular hypertrophy (LVH) while 4 had right ventricular hypertrophy (RVH) which were confirmed by electrocardiography (ECG) and echocardiography (ECHO). However, only 6 patients had cardiomegaly on chest radiography. Of the total 7 patients with LVH, 2 male patients had BP >120/80 mm Hg and ECG showed LVH which was confirmed by ECHO (LVEDD = 56 mm) while another patient had severe anaemia. Thus, the cardiac enlargement in these patients may be due to hypertension or anaemia. The cause of ventricular enlargement in the remaining patients could be due to some sort of cardiomyopathy linked to HCV infection as other contributory conditions such as chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), rheumatic heart disease (RHD) and other valvular heart diseases had been excluded from the present study.
Cardiomyopathic features, ventricular dysfunction and heart chamber enlargement were detected in some of the HCV seropositive patients by echocardiography. A male patient, non-hypertensive, non-diabetic, non-smoker but alcoholic was found to have hypertrophic cardiomyopathy on echocardiography. He presented with jaundice, hematemesis and malena and had liver problems with inflammation. Another male patient, a smoker and an alcoholic but not hypertensive presenting with abdominal pain, hematemesis and malena was found to have dilated cardiomyopathy on echocardiography. He had clinical and laboratory findings suggestive of liver problems and inflammation but was not cytopenic and had no kidney problems. A female patient, non-alcoholic, non-smoker, non-diabetic and non-hypertensive presenting with history of blood transfusion, abdominal distension, ascites and hypoalbuminemia was also found to have dilated cardiomyopathy on echocardiography. None had ischemic changes on ECG. Thus, it is seen that in both genders, dilated or hypertrophic cardiomyopathy may occur as cardiovascular complications in HCV seropositive patients. Possibility of ischemic dilated cardiomyopathy is unlikely as both patients were non-hypertensive nor were there any ischemic changes on ECG. However, the male patient could be having alcoholic cardiomyopathy. Alcohol has an additive effect on the disease progressive of chronic hepatitis C, so possibility of HCV dilated cardiomyopathy cannot be ruled out even in alcoholics. Infections, inflammatory conditions, HCV myocarditis or pericarditis and HCV dilated and hypertrophic cardiomyopathy are the likely possibilities to cause chamber enlargement, ventricular dysfunction, pleural and pericardial effusions in these patients. But to confirm the diagnosis, other relevant tests and myocardial biopsy are further needed. The increase in SGPT and ESR levels in HCV seropositive patients with dilated left atrium was found to be statistically significant and hence, high SGPT and high ESR may be good indicators of left atrium dilatation in HCV seropositive patients with left ventricular diastolic dysfunction. Hypertension, hyperglycemia, anemia and kidney dysfunction were not common amongst HCV seropositive patients with cardiac chamber enlargement or left ventricular diastolic dysfunction.
The present study was limited by the following:
Small sample size of 50 patients.
Cirrhotics and alcoholics were not excluded.
Certain tests like HCV RNA, cardiac catheterization and myocardial biopsy were not performed due to lack of facilities and expertise.
| Conclusion|| |
The study showed that the more progressed was the liver inflammation the more likely for cardiovascular affect of cardiac chamber enlargement and left ventricular diastolic dysfunction so an early diagnosis of chronic HCV infection and timely therapeutic intervention may decrease the associated cardiovascular manifestations.
| References|| |
|1.||Craxi A, Laffi G, Zignego AL. Hepatitis C virus (HCV) infection: A systemic disease. Mol Aspects Med 2008;29:85-95. |
|2.||Berenguer M, Wright TL. Hepatitis C. In: Feldman M, Friedman LS, Brandt LJ, editors. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management, 8 th ed. Philadelphia: Saunders Elsevier Inc; 2006. p.1682-712. |
|3.||Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, et al.Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C.Arthritis Rheum 1999;42:2204-12. |
|4.||Zignego AL, Bréchot C.Extrahepatic manifestations of HCV infection: Facts and controversies.J Hepatol 1999;31:369-76. |
|5.||Sanchez MJ, Bergasa NV.Hepatitis C associated cardiomyopathy: Potential pathogenic mechanisms and clinical implications.Med SciMonit 2008;14:RA55-63. |
|6.||Boddi M, Abbate R, Chellini B, Giusti B, Solazzo V, Soft F, et al. HCV infection facilitates asymptomatic carotid atherosclerosis: Preliminary report of HCV RNA localization in human carotid plaques. Dig Liver Dis 2007;39(Suppl 1):S55-60. |
|7.||Ishizaka N, Ishizaka Y, Takahashi E, ToodaEi, Hashimoto H, Nagai R, et al. Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening. Lancet 2002;359:133-5. |
|8.||Matsumori A, Matoba Y, Sasayama S. Dilated cardiomyopathy associated with hepatitis C virus infection. Circulation 1995;92:2519-25. |
|9.||Matsumori A. Hepatitis C virus infection and cardiomyopathies. Circ Res 2005;96:144-7. |
|10.||Butt AA, Xiaoqiang W, Budoff M, Leaf D, Kuller LH, Justice AC. Hepatitis C virus infection and the risk of coronary disease. Clin Infect Dis 2009;49:225-32. |
|11.||Ufearo H, Kambal K, Onojobi GO, Nouraie M, Agbemabiese C, Diaz S, et al. Complete blood count, measures of iron status and inflammatory markers in inner-city African Americans with undiagnosed hepatitis C seropositivity.ClinChimActa 2010;411:653-6. |
|12.||Langohr K, Sanvisens A, Fuster D, Tor J, Serra I, Rey-Joly C, et al. Liver enzyme alterations in HCV-monoinfected and HCV/HIV-coinfected patients. Open AIDS J 2008;2:82-8. |
|13.||Ijaz B, Ahmad W, Javed FT, Gull S, Sarwar MT, Kausar H, et al. Association of laboratory parameters with viral factors in patients with hepatitis C. Virol J 2011;8:361. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]