الفهرس 
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Abstract
Hepatitis C virus (HCV) is a global health problem that infects more than 170 million people worldwide and not less than 12% of the Egyptian population. After the acute stage, approximately 70–80% of patients progress to the chronic disease. HCV cirrhosis, fibrosis, and hepatocellular carcinoma are major sequelae of HCV chronic infection. The latter is one of the leading causes of liver transplantation, mortality and morbidity worldwide. Pegylated interferon (PEG IFN) and ribavirin combined therapy is the standard approved treatment for HCV and is only effective in around 50% of patients (Bader El Din et al., 2011).
Epstein Barr virus (EBV) is a gammaherpesvirus that causes a number of clinical syndromes, including acute mononucleosis and posttransplant lymphoproliferative disease, and has been linked to a number of malignancies. Most people have been exposed to EBV by early adulthood. After the initial infection, the virus becomes latent in B lymphocytes, and it can reactivate later in life to produce posttransplant lymphoproliferative disease in immunocompromised transplant patients, central nervous system lymphoma in AIDS patients, or a more classic acute EBV-related viral illness in some patients infected with other viruses (Klutts et al., 2009).
The importance and the interest of HCMV as a pathogen have increased over the past two decades. Approximately 70-100% of the world’s populations are carriers of the virus and it has become the most common cause of severe morbidity and mortality in immune compromised individuals. A primary HCMV infection is followed by a life-long persistence of the virus in a latent state, and reactivation may occur later in life. Therefore, reactivation of the virus is seen during periods of down-regulation of the immune system, such as drug treatment and illness-related stress, or during on-going activation of the immune system such as inflammatory diseases, or co-infection with other pathogens. HCMV can infect virtually all organ tissues, but manifestations of organ involvement generally include symptoms from the liver, the lungs, the intestine and the CNS (Tabll et al., 2011).
Viral co-infections may modulate disease expression, enhance pathogenicity, and lead to greater cumulative immunosuppression in the host. The pathophysiological basis of these may be direct virus-virus interactions, effect of cohabitating viruses on host cell function, or impaired host immune responses, Sequelae of coinfection of viruses may also result from direct interactions between the viruses—for example, via regulatory genes with the ability to transactivate or repress the expression of the genes of cohabitating virus, or from yet unknown factors (Singh, 2005).
In this study, we investigated the incidence of EBV and CMV infections in Egyptian HCV patients who underwent interferon based therapy. The patients were divided into two main groups: chronic HCV group I (n=100) which has been classified into two subgroups according to their responsiveness to the therapy: Responders (n=74) and Non responders (n=26) in comparison with healthy controls (n=20).
The study design was comparative cross sectional. Regarding demographic characteristics, There was significant higher mean age in non-responder than responder patients (p<0.01). Although There were non statistically significant differences between both groups regarding BMI, frequency and percentage of gender (p>0.05).
Regarding hematological parameters (hemoglobin , platelets count, WBCs count) there were non statistically significant differences between studied responder and non-responder groups regarding hemoglobin, platelets and leucocytes count (p>0.05).
Regarding biochemical markers (ALT, AST, Albumin, Total bilirubin, Indirect billirubin, Creatinine) there were non statistically significant differences between studied responder and non-responder groups (p>0.05).
AFP levels were significantly higher in non-responder than responder patients (5.2 ng/ml versus 3.5 ng/ml, respectively) (p<0.05).
Regarding histopathological parameters of the studied responder and non-responder groups. There were non statistically significant differences between both groups regarding fibrosis stage and activity grade (p>0.05).
Regarding HCV viral loads, the mean values of HCV RNA levels were significantly higher in non-responder than responder patients (0.72x106 versus 0.34 x106, respectively) (p<0.05).
Regrading EBV DNA peripheral blood load, The results showed that there was statistically significant higher percentage of EBV 500-2000 copies/ml in the control group than HCV patients group (35% versus 7%, respectively) (p<0.01). Also, there was statistically significant higher percentage of undetectable EBV in HCV patients group than control group (82% versus 60%, respectively) (p<0.05). The results also showed that there was statistically significant higher percentage of undetectable EBV in non-responder than responder patients (96.2% versus 77%, respectively) (p<0.01), while there was statistically significant higher percentage of EBV >2000 copies/ml in responder than non-responder patients (14.9% versus 0.0%, respectively) (p<0.05)
Regarding serological findings of EBV , results showed that there were non statistically significant differences between the studied responder and non-responder groups regarding all EBV antibodies as detected by ELISA (p>0.05).
Regarding the interpretation of EBV results as detected by ELISA of the studied responder and non-responder groups. There was statistically significant higher percentage of past infection among non-responder than responder patients (100% versus 81.8%, respectively) (p<0.05).
Regarding serological findings of CMV , results showed There were non statistically significant differences between the studied responder and non-responder groups regarding CMV IgM and CMV IgG antibodies as detected by ELISA (p>0.05).
Regarding the interpretation of CMV results as detected by ELISA of the studied responder and non-responder groups. There was non statistically significant difference between both groups regarding interpretation of CMV results (p>0.05).
In conclusion , the results of this study suggest that there is a unidirectional relation between EBV and HCV in our study subjects ,this explained by the high percentage of EBV viral load in responders and low EBV viral loads in non-responders. While CMV may have no impact on responsiveness of HCV chronic patients to interferon based therapy.
Long-term follow-up is recommended, because very late HCV relapses may occur in co-infected patients. These data explain the complexity of viral dominance in patients infected with multiple hepatitis viruses, and this has significant importance for treatment decisions.