الفهرس 
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Abstract
Hepatitis continues to be a major health threat in both developed and developing nations. Hepatitis C virus (HCV) was first described in 1989 using molecular biology techniques and visualized in 1990s. So far, there are seven major groups or genotypes numbered 1 to 7 although some experts believe that there may be as many as 11; with significant differences in their global distribution and prevalence.
The major burden from HCV infection comes from chronic infection. Estimates indicate that three to four million persons are newly infected each year, about 170 million people are chronically infected and at risk of developing liver disease including cirrhosis and liver cancer, and 350,000 to 500,000 deaths occur each year due to all HCV-related causes.
HCV infection is a major public health burden in Egypt, which has the highest prevalence rate of HCV in the world, with an estimated prevalence of 14.7%, and is considered a major cause of chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and liver transplantation in the country. Nosocomial transmission has been, and probably stills, the most common route for new infections. The genotype distribution in Egypt is mainly genotype 4 (HCV-G4) which is responsible for more than 90% of the infections, while the remaining infections are due to HCV-G1.
HCV infection can present as acute or chronic hepatitis. Probably as many as
75%-85% infected people fail to clear the virus during the acute phase of the disease and become chronic carriers. chronic infection is often asymptomatic, until evidence of liver failure becomes clinically apparent.
In 2004, a new entity of HCV infection was first described in patients with persistently elevated liver function tests who were anti-HCV and serum HCV RNA negative and was termed occult HCV infection (OCI). OCI is defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, but HCV RNA is identifiable in serum, PBMCs and/or liver tissue by molecular tests of enhanced sensitivity.
OCI has also been described in anti-HCV positive, serum HCV-RNA negative subjects with normal values of liver enzymes who had cleared their HCV infections, either spontaneously or after treatment; or in asymptomatic HCV carriers of whom nearly 90% have detectable viral RNA in liver and in PBMCs.
While the diagnosis of HCV is made by the presence of anti-HCV antibody and/or HCV RNA in the blood, the gold standard method for diagnosing OCI is by detection of HCV RNA in the liver. However, as liver biopsies are not readily available, an alternative method for diagnosing OCI could be to look for HCV RNA in PBMCs.
The aim of this study was to determine the frequency of OCI among blood donors by testing anti-HCV and HCV RNA negative blood donors with abnormal liver function for HCV RNA presence in PBMCs.
A total of 520 blood donors at the blood bank of the Medical Research Institute, Alexandria University were included in this study. All relevant information was collected from each patient including personal data, habits and medical data.
Blood samples were collected from all donors upon donation. Sera were separated by centrifugation and were tested for antibodies against HCV, hepatitis B surface antigen (HBs Ag) and antibodies against HIV by ELISA. Twenty donors were excluded due to positive HCV and/or HBV. For five hundred anti-HCV negative donors ALT levels were measured. Out of the 500 donors included, thirty five donors (7%) had their ALT higher than normal values.
Six months later, the thirty five donors with elevated ALT were recalled and another blood sample was withdrawn, and sera were used to retest ALT levels. Out of thirty five donors, twenty seven donors (5.4% out of 500 donors) still had elevated ALT values and those were the subjects who were selected for detection of OCI.
The sera of the second blood sample were used also to test HCV RNA presence and/or absence. PBMCs were separated by Ficoll density-gradient centrifugation for those thirty five donors from the second blood sample.
The donors with persistently elevated liver functions with unknown cause were further tested for HCV RNA in serum, by conventional PCR followed by gel electrophoresis. None of them had HCV RNA in their serum; thus they were fulfilling occult HCV definition: anti-HCV and serum HCV RNA negative and then were further tested for HCV RNA in PBMCs, by TaqMan® probe-based technology. None of the twenty seven donors with persistently elevated liver functions had HCV RNA in their PBMCs.
There is limited number of studies on OCI in which OCI was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. (216) Using different techniques, OCI was also described in cryptogenic liver cirrhosis, hepatocellular carcinoma, lymphoproliferative disorders, hemodialysis patients with abnormal values of liver enzymes of unknown origin, and even in healthy subjects without evidence of hepatic disease.
It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic HCV infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of OCI would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system. (216)