الفهرس 
Lymphoproliferative DisordersOnly 14 pages are availabe for public view
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Abstract
B-cell LPDs are a heterogeneous group of pathologies ranging from a minor expansion of a B-cell population with no clinical significance to an aggressive high-grade lymphoma. Egypt has the highest prevalence of lymphoma worldwide, mainly NHL. Such proliferations of B cells apparently can be triggered by a number of viruses.
A causative association between hepatotropic viruses, especially HCV, and malignant B-cell LPDs has been demonstrated utilizing epidemiologic data, biologic and molecular investigations, as well as clinical observations. They indicate that HCV infects not only hepatocytes but also cells in extrahepatic compartments, particularly those in the immune and the central nervous systems. Concerning infection of immune cells, HCV replication was shown in circulating T and B-lymphocytes and monocytes from patients with chronic as well as persistent low level (occult) infections.
Occult HCV infection has been considered a new pathological entity which is characterized by the presence of HCV RNA in liver cells and PBMCs in the absence of detectable viral RNA in serum by standard assays. It can be found in anti-HCV positive patients with normal liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology.
In light of that, the aim of this study was to identify the possible association between OCI and malignant LPDs and to compare the prevalence of OCI in LPD patients versus healthy subjects.
To achieve this aim, the study was conducted on 32 newly diagnosed patients with LPDs whose mean age was 53.84±11.34 years, with male: female ratio of 3:1. Patients with positive HBsAg, HIV, EBV or CMV antibodies were excluded from the study. Twenty-seven age and sex matched healthy subjects were included as a control group whose mean age was 45.73±11.14 years, with male: female ratio of 2:1, and were selected to be negative for serum HCV Ab and serum HCV RNA. All the patients were subjected to full history taking, clinical examination, CBC with differential white cell count, BM aspirate, immunophenotyping, BM biopsy, lymph node biopsy, abdominal ultrasound and CT, complete liver and kidney function tests and assay of beta 2 microglobulin. Both patients and controls were subjected to ELISA for detection of HBsAg, HCV, HIV, EBV and CMV antibodies, real time PCR detection of HCV-RNA in plasma and PBMCs, and conventional and immuno-electron microscopic analysis of PBMCs.
Our findings demonstrated a significantly higher percentage of positive OCI among LPD patients compared to healthy subjects. Results also showed that positive OCI LPD patients were equally distributed among the studied NHL and CLL groups.
The present study divided LPD patients into 3 groups: positive OCI, positive HCV, and negative OCI/negative HCV groups. When these groups were compared with each other as regards the demographic, clinical and laboratory data, it was found that positive OCI group showed a significantly higher percentage of patients with hepatomegaly and splenomegaly compared to the other 2 groups. Positive HCV group showed a significantly higher level of hemoglobin compared to the other 2 groups. Positive HCV group showed a significantly higher percentage of positive HCV Ab and positive HCV PCR in plasma as well as significantly higher copy number of HCV in plasma and PBMCs compared to the other 2 groups. Both positive HCV and positive OCI groups showed a significantly higher percentage of positive HCV PCR in PBMCs compared to negative OCI/negative HCV group. On the other hand, there was no statistically significant difference between the 3 groups regarding the remaining data.
On comparing between positive OCI, and negative OCI/negative HCV LPD patients groups as regards the studied parameters, it was found that positive OCI group showed a significantly higher count of PB lymphocytes and higher level of B2M as well as significantly higher percentage of lymphocytes in BM aspirate and infiltration in BM biopsy compared to negative OCI/negative HCV group. Positive OCI group also showed a significantly higher percentage of positive HCV PCR in PBMCs and significantly higher copy number of HCV in PBMCs compared to the other group.
Ultrastructural examination of PBMCs revealed the presence of intracytoplasmic vacuoles enclosing viral like particles, which were more in positive HCV patients than those seen in positive OCI patients.
In conclusion, the current study demonstrated the existence of OCI among Egyptian LPD patients. Therefore, the possibility of OCI should be considered in patients with LPDs as the existence of HCV-RNA in immune cells and liver tissue, as its reservoir, can lead to relapse or cause overt infection even after treatment. Thus, the evaluation of OCI in those patients might help in the choice of treatment modalities (immunotherapy, chemotherapy and antiviral therapy) which may help to control tumor progression as well as reduce post chemotherapy complications related to HCV infection, thus achieving a higher