Background. Occult hepatitis C virus infection (OCI) was identified as a new form of Hepatitis C virus (HCV), characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood cells only. Aim. The aim of this study was to investigate the occurrence of OCI in Egyptian patients with lymphoproliferative disorders (LPDs) and to compare its prevalence with that of HCV in those patients. Subjects and Methods. The current study included 100 subjects, 50 of them were newly diagnosed cases having different lymphoproliferative disorders (patients group), and 50 were apparently healthy volunteers (controls group). HCV antibodies were detected by ELISA, HCV RNA was detected in serum and peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction(RT-PCR), and HCV genotype was detected by INNO-LiPA. Results. OCI was detected in 20% of patients group, compared to only 4% OCI in controls group. HCV was detected in 26% of patients group with a slightly higher prevalence. There was a male predominance in both HCV and OCI. All HCV positive patients were genotype 4. Conclusion. Our data revealed occurrence of occult HCV infection in Egyptian LPD patients at a prevalence of 20% compared to 26% of HCV. 1. Introduction Chronic hepatitis C virus (HCV) infection remains a global health threat with 175 million carriers worldwide. Approximately 3% of the worldwide population is infected with the hepatitis C virus (HCV) [1]. The prevalence of HCV infection varies throughout the world, with the highest prevalence reported in Egypt [2]. HCV is an RNA virus that belongs to the family of flaviviruses [3]. The natural targets of HCV are hepatocytes and, possibly, B lymphocytes [4, 5]. A new form of chronic HCV infection named occult hepatitis C virus (OCI) was described by Castillo et al., 2004 [6]. This infection is characterized by absence of anti-HCV antibodies (Abs) and HCV RNA in serum with elevated liver function tests in the presence of HCV-RNA in the liver [6]. Furthermore, about 70% of patients with occult HCV infection also have HCV RNA in their peripheral blood mononuclear cells (PBMCs); the genomic and the antigenomic HCV RNA have also been detected in these cells [7]. Although detection of genomic HCV-RNA strand in liver biopsy specimen is the gold standard and the most accurate method for the diagnosis of occult HCV infection, testing for HCV-RNA in PBMCs is an alternative and easy to do when a liver biopsy is not available [8, 9]. Lymphoproliferative disorders is a term that
References
[1]
WHO, “Hepatitis C-global prevalence (update),” The Weekly Epidemiological Record, vol. 74, pp. 425–427, 1999.
[2]
C. Frank, M. K. Mohamed, G. T. Strickland et al., “The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt,” Lancet, vol. 355, no. 9207, pp. 887–891, 2000.
[3]
B. Robertson, G. Myers, C. Howard et al., “Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization,” Archives of Virology, vol. 143, no. 12, pp. 2493–2503, 1998.
[4]
M. Okuda, K. Hino, M. Korenaga, Y. Yamaguchi, Y. Katoh, and K. Okita, “Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver,” Hepatology, vol. 29, no. 1, pp. 217–222, 1999.
[5]
A. L. Zignego, M. De Carli, M. Monti et al., “Hepatitis C virus infection of mononuclear cells from peripheral blood and liver infiltrates in chronically infected patients,” Journal of Medical Virology, vol. 47, no. 1, pp. 58–64, 1995.
[6]
I. Castillo, M. Pardo, J. Bartolomé et al., “Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknow,” Journal of Infectious Diseases, vol. 189, no. 1, pp. 7–14, 2004.
[7]
J. M. López-Alcorocho, E. Rodríguez-I？igo, I. Castillo et al., “The role of genomic and antigenomic HCV-RNA strands as predictive factors of response to pegylated interferon plus ribavirin therapy,” Alimentary Pharmacology and Therapeutics, vol. 25, no. 10, pp. 1193–1201, 2007.
[8]
G. Barril, I. Castillo, M. D. Arenas et al., “Occult hepatitis C virus infection among hemodialysis patients,” Journal of the American Society of Nephrology, vol. 19, no. 12, pp. 2288–2292, 2008.
[9]
F. Franzin, D. G. Efremov, G. Pozzato, P. Tulissi, F. Batista, and O. R. Burrone, “Clonal B-cell expansions in peripheral blood of HCV-infected patients,” British Journal of Haematology, vol. 90, no. 3, pp. 548–552, 1995.
[10]
F. Marcucci and A. Mele, “Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities,” Blood, vol. 117, no. 6, pp. 1792–1798, 2011.
[11]
S. C. Gordon, “Extrahepatic manifestations of hepatitis C,” Digestive Diseases, vol. 14, no. 3, pp. 157–168, 1996.
[12]
R. Idilman, A. Colantoni, N. De Maria, S. Alkan, S. Nand, and D. H. Van Thiel, “Lymphoproliferative disorders in chronic hepatitis C,” Journal of Viral Hepatitis, vol. 11, no. 4, pp. 302–309, 2004.
[13]
L. Dal Maso and S. Franceschi, “Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies,” Cancer Epidemiology Biomarkers and Prevention, vol. 15, no. 11, pp. 2078–2085, 2006.
[14]
A. Nieters, B. Kallinowski, P. Brennan et al., “Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH,” Gastroenterology, vol. 131, no. 6, pp. 1879–1886, 2006.
[15]
A. L. Zignego, C. Giannini, M. Monti, and L. Gragnani, “Hepatitis C virus lymphotropism: lessons from a decade of studies,” Digestive and Liver Disease, vol. 39, supplement 1, pp. S38–S45, 2007.
[16]
M. H. Chen, L. T. Hsiao, T. J. Chiou et al., “High prevalence of occult hepatitis B virus infection in patients with B cell non-Hodgkin's lymphoma,” Annals of Hematology, vol. 87, no. 6, pp. 475–480, 2008.
[17]
G. M. El-Sayed, W. S. Mohamed, M. A. Nouh, M. M. Moneer, and H. A. El-Mahallawy, “Viral genomes and antigen detection of hepatitis B and C viruses in involved lymph nodes of Egyptian non-Hodgkin's lymphoma patients,” The Egyptian Journal of Immunology, vol. 13, no. 1, pp. 105–114, 2006.
[18]
L. Goldman, S. Ezzat, N. Mokhtar et al., “Viral and non-viral risk factors for non-Hodgkin's lymphoma in Egypt: heterogeneity by histological and immunological subtypes,” Cancer Causes and Control, vol. 20, no. 6, pp. 981–987, 2009.
[19]
I. Gouda, O. Nada, S. Ezzat et al., “Immunohistochemical detection of hepatitis C virus (genotype 4) in B-cell NHL in an Egyptian population: correlation with serum HCV-RNA,” Applied Immunohistochemistry and Molecular Morphology, vol. 18, no. 1, pp. 29–34, 2010.
[20]
M. K. El-Awady, S. S. Youssef, M. H. Omran, A. A. Tabll, W. T. El Garf, and A. M. Salem, “Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection,” BMC Infectious Diseases, vol. 6, article no. 91, 2006.
[21]
R. Idilman, Y. Bozkus, G. Seval et al., “Lymphoproliferative disorders in individuals with chronic hepatitis b and C in the Turkish population,” Journal of Medical Virology, vol. 83, no. 6, pp. 974–980, 2011.
[22]
T. N. Q. Pham, C. S. Coffin, and T. I. Michalak, “Occult hepatitis C virus infection: what does it mean?” Liver International, vol. 30, no. 4, pp. 502–511, 2010.
[23]
L. Goldman, S. Ezzat, N. Mokhtar et al., “Viral and non-viral risk factors for non-Hodgkin's lymphoma in Egypt: heterogeneity by histological and immunological subtypes,” Cancer Causes and Control, vol. 20, no. 6, pp. 981–987, 2009.
[24]
H. Zaghloul and W. El-Sherbiny, “Detection of occult hepatitis C and hepatitis B virus infections from peripheral blood mononuclear cells,” Immunological Investigations, vol. 39, no. 3, pp. 284–291, 2010.
[25]
L. De Marco, A. Gillio-Tos, V. Fiano et al., “Occult HCV infection: an unexpected finding in a population unselected for hepatic disease,” PloS One, vol. 4, no. 12, article no. e8128, 2009.
[26]
T. N. Q. Pham, S. E. Mercer, and T. I. Michalak, “Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles,” Journal of Viral Hepatitis, vol. 16, no. 8, pp. 547–556, 2009.
[27]
Y. Kondo, V. M. H. Sung, K. Machida, M. Liu, and M. M. C. Lai, “Hepatitis C virus infects T cells and affects interferon-γ signaling in T cell lines,” Virology, vol. 361, no. 1, pp. 161–173, 2007.
[28]
F. Bokharaei-Salim, H. Keyvani, S. H. R. Monavari et al., “Occult hepatitis C virus infection in Iranian patients with cryptogenic liver disease,” Journal of Medical Virology, vol. 83, no. 6, pp. 989–995, 2011.
[29]
Y. Saad, S. Zakaria, I. Ramzy, et al., “Prevalence of occult hepatitis C in Egyptian patients with non alcoholic fatty liver disease,” Open Journal of Internal Medicine, vol. 1, pp. 33–37, 2011.
[30]
S. C. Ray, R. R. Arthur, A. Carella, J. Bukh, and D. L. Thomas, “Genetic epidemiology of hepatitis C virus throughout Egypt,” Journal of Infectious Diseases, vol. 182, no. 3, pp. 698–707, 2000.
[31]
I. Castillo, E. Rodríguez-I？igo, J. M. López-Alcorocho, J. Bartolomé, M. Pardo, and V. Carre？o, “Comparative study on the clinical and virological characteristics among patients with single occult hepatitis B virus (HBV), single occult hepatitis C virus (HCV) and occult HBV and HCV dual infection,” Journal of Medical Virology, vol. 79, no. 3, pp. 236–241, 2007.
