World Journal of Cardiovascular Diseases, 2013, 3, 499-505 WJCD http://dx.doi.org/10.4236/wjcd.2013.38079 Published Online November 2013 (http://www.scirp.org/journal/wjcd/ ) Hyperhomoysteinemia as a risk factor for coronary heart diseases in chronic hepatitis C patients Ali Raza Kazmi 1 , Andleeb Hanif 1,2 , Muhammad Ismail 1 , Javaria Qazi 2 1 Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan 2 Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan Email: drsakazmi@gmail.com Received 20 August 2013; revised 28 September 2013; accepted 15 October 2013 Copyright © 2013 Ali Raza Kazmi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Hepatitis C virus is one of the major health problems worldwide. It affects mainly the liver but several ex- trahepatic manifestations are also accounted. Chronic hepatitis C patients are at an increased risk of devel- oping hepatic steatosis, which share many clinical fea- tures with the metabolic syndrome. Hepatic steatosis has also been associated with elevated levels of mark- ers of inflammation such as homocysteine, identified as hyperhomocysteinemia (HHC). HHC due to Me- thylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T polymorphism, was recently as- sociated with coronary heart diseases (CHD) in chro- nic hepatitis C (CHC) patients. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver metabolism. Deficiencies of micronutrients (folate, vitamin B 6 and possibly vita- min B 12) along with mild hyperhomocysteinemia, perhaps, act synergistically with other classical risk factors to further increase the risk of CHD. Clinical data indicate that HHC is associated with an increa- sed incidence of CHD as well as with the severity of the disease in CHC patients. In conclusion, HHC might be a potential aetiological factor of CHD in CHC patients. The aim of this review is to investigate the progression of coronary heart diseases in chronic hepatitis C patients and correlate with levels of homo- cysteine in concurrence to genetic defects and nutri- ent deficiencies. However, future studies need to clari- fy the mechanistic role of HHC in CHD and CHC as a useful paradigm with most interesting therapeutic im- plications. Keywords: Hepatitis C Virus; Hyperhomocysteinemia (HHC); Coronary Heart Diseases (CHD); Chronic Hepatitis C (CHC) 1. INTRODUCTION Chronic infection with hepatitis C virus (HCV) is one of the leading causes of chronic liver disease; about 170 million people worldwide are estimated to be infected. Hepatitis C virus infection causes acute symptoms in only 15% of patients exposed to HCV infection while about 80% patients develop chronic infection [1]. Chro- nic hepatitis C results in formation of high levels of free radicals in the liver cells, which put serious oxidative stress depleting protective antioxidants and eventually kill the liver cells. A hepatitis screen is recommended for patients whereby the disease can be diagnosed by the presence of antibodies for hepatitis C or by the direct presence of the virus or viral products in the blood [2]. 2. ASSOCIATED RISKS: CHRONIC HEPATITIS C Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV infection frequently does not resolve, leading to chronic hepatitis with increasing risk of developing hepatic fibrosis, steatosis, liver cirrhosis, hepatocellular carcinoma, metabolic syndromes, arthro- sclerosis and extrahepatic diseases [3]. The combination of pegylated interferon (IFN)-a and ribavirin is the only treatment for chronic HCV infections with proven effi- cacy. Unfortunately, this therapeutic strategy results in a low sustained virologic response (SVR), defined as an ab- sence of detectable serum HCV-RNA at six months after completion of antiviral therapy; SVR is achieved in less than 50% of treated patients that have HCV genotype 1 and a high viral load [4]. There is evidence indicating that SVR is associated with long-term clearance of HCV infection and lower HCV-related complications [5,6]. However, IFN-a in combination with ribavirin is gene- rally not well tolerated, and the adverse side effects may OPEN ACCESS