A New Twist to a Chronic HCV Infection: Occult Hepatitis C

Gastroenterology Research and Practice

Volumn 2015, Issue , 2015, Pages

  Attar, Bashar M ^a,b   Van Thiel, David ^c  

^a Cook County Health and Hospitals System ^*  (United States)

^b RUSH UNIVERSITY MEDICAL CENTER   (United States)

^c Advanced Liver and Gastrointestinal Disease Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PEGINTERFERON ALPHA2A PLUS RIBAVIRIN; VIRUS RNA;

ANTIVIRAL THERAPY; CHRONIC HEPATITIS C; CLINICAL FEATURE; FOLLOW UP; HEPATITIS C VIRUS; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; OCCULT HEPATITIS C INFECTION; PERIPHERAL BLOOD MONONUCLEAR CELL; PREVALENCE; PROGNOSIS; REVIEW; VIRUS REPLICATION;

EID: 84936797573     PISSN: 16876121     EISSN: 1687630X     Source Type: Journal    
DOI: 10.1155/2015/579147     Document Type: Review

References (136)

1. J.-M. Pawlotsky, "Therapy of hepatitis C: from empiricism to eradication, " Hepatology, vol. 43, no. 2, pp. S207-S220, 2006.
2. B. Hajarizadeh, J. Grebely, and G. J. Dore, "Epidemiology and natural history of HCV infection, " Nature Reviews Gastroenterology and Hepatology, vol. 10, no. 9, pp. 553-562, 2013.
3. J.-M. Pawlotsky, "New hepatitis C therapies: the toolbox, strategies, and challenges, " Gastroenterology, vol. 146, no. 5, pp. 1176-1192, 2014.
4. E. R. Feeney and R. T. Chung, "Antiviral treatment of hepatitis C, " The BritishMedical Journal, vol. 348, Article IDg3308, 2014.
5. A. Slomski, "WHO issues guidelines on HCV amid drug cost controversy, " The Journal of the American Medical Association, vol. 311, no. 22, pp. 2262-2263, 2014.
6. R. Chou, D. Hartung, B. Rahman, N. Wasson, E. B. Cottrell, and R. Fu, "Comparative effectiveness of antiviral treatment for hepatitisCvirus infection in adults: A systematic review, " Annals of Internal Medicine, vol. 158, no. 2, pp. 114-123, 2013.
7. M. Bourlière, A. Wendt, H. Fontaine, C. Hézode, S. Pol, and J. P. Bronowicki, "How to optimize HCV therapy in genotype 1 patients with cirrhosis, " Liver International, vol. 33, no. 1, pp. 46-55, 2013.
8. L. Wei andA. S. F. Lok, "Impact of newhepatitis c treatments in different regions of the world, " Gastroenterology, vol. 146, no. 5, pp. 1145-1150, 2014.
9. T. N. Q. Pham, S. A. MacParland, P. M. Mulrooney, H. Cooksley, N. V. Naoumov, and T. I. Michalak, "Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C, " Journal of Virology, vol. 78, no. 11, pp. 5867-5874, 2004.
10. 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 unknown, " Journal of Infectious Diseases, vol. 189, no. 1, pp. 7-14, 2004.
11. L. de Marco, A. Gillio-Tos, V. Fiano et al., "Occult HCV infection: An unexpected finding in a population unselected for hepatic disease, " PLoSONE, vol. 4, no. 12, Article IDe8128, 2009.
12. M.-W. Welker and S. Zeuzem, "Occult hepatitisC: howconvincing are the current data?" Hepatology, vol. 49, no. 2, pp. 665-675, 2009.
13. V. Carreño, J. Bartolomé, I. Castillo, and J. A. Quiroga, "New perspectives in occult hepatitis C virus infection, " World Journal of Gastroenterology, vol. 18, no. 23, pp. 2887-2894, 2012.
14. I. Castillo, E. Rodrguez-Iñigo, J. Bartolomé et al., "Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection, " Gut, vol. 54, no. 5, pp. 682-685, 2005.
15. T. N. Q. Pham and T. I. Michalak, "Occult hepatitis C virus infection and its relevance in clinical practice, " Journal of Clinical and Experimental Hepatology, vol. 1, no. 3, pp. 185-189, 2011.
16. V. Carreño, M. Pardo, J. M. López-Alcorocho, E. Rodrguez-Iñigo, J. Bartolomé, and I. Castillo, "Detection of hepatitis C virus (HCV) RNA in the liver of healthy, anti-HCV antibodypositive, serum HCV RNA-negative patients with normal alanine aminotransferase levels, " Journal of Infectious Diseases, vol. 194, no. 1, pp. 53-60, 2006.
17. F. Bernardin, L. Tobler, I. Walsh, J. D. Williams, M. Busch, and E. Delwart, "Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia, " Hepatology, vol. 47, no. 5, pp. 1446-1452, 2008.
18. B. Pinarbasi, M. Bozaci, F. Akyuz et al., "The presence of HCVRNA in the peripheral blood mononuclear cells of the individuals with isolated anti HCV positivity: is HCV hiding out" Journal ofHepatology, vol. 48, supplement 2, p. S222, 2008.
19. T. N. Q. Pham, C. S. Coffin, andT. I. Michalak, "Occult hepatitis C virus infection: what does it mean?" Liver International, vol. 30, no. 4, pp. 502-511, 2010.
20. G. H. Haydon, L. M. Jarvis, C. S. Blair et al., "Clinical significance of intrahepatic hepatitis C virus levels in patients with chronic HCV infection, " Gut, vol. 42, no. 4, pp. 570-575, 1998.
21. S. Barrett, N. Kieran, E. Ryan, J. C. O'Keane, and J. Crowe, "Intrahepatic hepatitis C viralRNA status of serumpolymerase chain reaction-negative individuals with histological changes on liver biopsy, " Hepatology, vol. 33, no. 6, pp. 1496-1502, 2001.
22. Y. Sugiyasu, N. Yuki, T. Nagaoka et al., "Histological improvement of chronic liver disease after spontaneous serum hepatitis C virus clearance, " Journal ofMedical Virology, vol. 69, no. 1, pp. 41-49, 2003.
23. M. Tomimatsu, H. Endou, H. Takahashi et al., "Negative strand of hepatitis C virus RNA in the liver of patients with chronic hepatitis C after interferon treatment, " Journal of Gastroenterology and Hepatology, vol. 12, no. 9-10, pp. 629-632, 1997.
24. 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.
25. T. N. Q. Pham, D. King, S. A. MacParland et al., "Hepatitis C virus replicates in the same immune cell subsets in chronic hepatitis C and occult infection, " Gastroenterology, vol. 134, no. 3, pp. 812-822, 2008.
26. M. Hoare, W. T. H. Gelson, S. M. Rushbrook et al., "Histological changes in HCV antibody-positive, HCV RNA-negative subjects suggest persistent virus infection, " Hepatology, vol. 48, no. 6, pp. 1737-1745, 2008.
27. T. N. Q. Pham, P. M. Mulrooney-Cousins, S. E. Mercer et al., "Antagonistic expression of hepatitis C virus and alpha interferon in lymphoid cells during persistent occult infection, " Journal of Viral Hepatitis, vol. 14, no. 8, pp. 537-548, 2007.
28. M. Radkowski, J. F. Gallegos-Orozco, J. Jablonska et al., "Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C, " Hepatology, vol. 41, no. 1, pp. 106-114, 2005.
29. I. Castillo, E. Rodrguez-Iñigo, J. M. López-Alcorocho, M. Pardo, J. Bartolomé, and V. Carreño, "Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment, " Clinical Infectious Diseases, vol. 43, no. 10, pp. 1277-1283, 2006.
30. A. Ciancio, A. Smedile, C. Giordanino et al., "Long-termfollowup of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: Are they really cured?" American Journal of Gastroenterology, vol. 101, no. 8, pp. 1811-1816, 2006.
31. J. A. Quiroga, S. Llorente, I. Castillo et al., "Virus-specific T-cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection, " Journal of Medical Virology, vol. 78, no. 9, pp. 1190-1197, 2006.
32. J. F. Gallegos-Orozco, J. Rakela, M. J. Rosati, H. E. Vargas, and V. Balan, "Persistence of hepatitis C virus in peripheral blood mononuclear cells of sustained viral responders to pegylatedinterferon and ribavirin therapy, " Digestive Diseases and Sciences, vol. 53, no. 9, pp. 2564-2568, 2008.
33. G. Di Liberto, A.-M. Roque-Afonso, R. Kara et al., "Clinical and therapeutic implications of hepatitis C virus compartmentalization, " Gastroenterology, vol. 131, no. 1, pp. 76-84, 2006.
34. N. Tsuda, N. Yuki, K. Mochizuki et al., "Long-term clinical and virological outcomes of chronic hepatitis C after successful interferon therapy, " Journal of Medical Virology, vol. 74, no. 3, pp. 406-413, 2004.
35. T. N. Q. Pham, S. A. MacParland, C. S. Coffin, S. S. Lee, F. R. Bursey, and T. I. Michalak, "Mitogen-induced upregulation of hepatitis C virus expression in human lymphoid cells, " Journal of General Virology, vol. 86, no. 3, pp. 657-666, 2005.
36. T. N. Q. Pham and T. I. Michalak, "Hepatitis C virus in peripheral blood mononuclear cells of individuals with isolated anti-hepatitis C virus antibody reactivity, " Hepatology, vol. 48, no. 1, pp. 350-351, 2008.
37. S. A. MacParland, T. N. Q. Pham, C. S. Guy, and T. I. Michalak, "Hepatitis C virus persisting after clinically apparent sustained virological response to antiviral therapy retains infectivity in vitro, " Hepatology, vol. 49, no. 5, pp. 1431-1441, 2009.
38. K. Katayama, J. Kumagai, Y. Komiya et al., "Titrationof hepatitis C virus in chimpanzees for determining the copy number required for transmission, " Intervirology, vol. 47, no. 1, pp. 57-64, 2004.
39. P. Halfon, M. Bourlière, D. Ouzan et al., "Occult hepatitis C virus infection revisited with ultrasensitive real-time PCR assay, " Journal of Clinical Microbiology, vol. 46, no. 6, pp. 2106-2108, 2008.
40. S. L. George, B. R. Bacon, E. M. Brunt, K. L. Mihindukulasuriya, J. Hoffman, and A. M. Di Bisceglie, "Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5-year follow-up of 150 patients, " Hepatology, vol. 49, no. 3, pp. 729-738, 2009.
41. S. Maylin, M. Martinot-Peignoux, R. Moucari et al., "Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C, " Gastroenterology, vol. 135, no. 3, pp. 821-829, 2008.
42. S. Naga, S. H. T. Raghuraman, and J. R. B. Liang, "Minute levels of HCV RNA persist for an extended period of time after clinical recovery from hepatitis C but are ultimately cleared, " in Proceedings of the 15th International Symposium on Hepatitis C Virus and Related Viruses, p. 66, San Antonio, Tex, USA, October 2008.
43. P. Marcellin, N. Boyer, A. Gervais et al., "Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-therapy, " Annals of Internal Medicine, vol. 127, no. 10, pp. 875-881, 1997.
44. A.-M. Roque-Afonso, D. Ducoulombier, G. Di Liberto et al., "Compartmentalization of hepatitis C virus genotypes between plasma and peripheral blood mononuclear cells, " Journal of Virology, vol. 79, no. 10, pp. 6349-6357, 2005.
45. I. Castillo, J. Bartolomé, J. A. Quiroga, G. Barril, and V. Carreño, "Hepatitis C virus infection in the family setting of patients with occult hepatitis C, " Journal ofMedical Virology, vol. 81, no. 7, pp. 1198-1203, 2009.
46. A. Y. Chen, M. Zeremski, R. Chauhan, I. M. Jacobson, A. H. Talal, and T. I. Michalak, "Persistence of hepatitis C virus during and after otherwise clinically successful treatment of chronic hepatitis Cwith standard pegylated interferon-2b and ribavirin therapy, " PLoS ONE, vol. 8, no. 11, Article ID e80078, 2013.
47. M. Inokuchi, T. Ito, H. Nozawa et al., "Lymphotropic hepatitis C virus has an interferon-resistant phenotype, " Journal of Viral Hepatitis, vol. 19, no. 4, pp. 254-262, 2012.
48. 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.
49. J. Bartolomé, J. M. López-Alcorocho, I. Castillo et al., "Ultracentrifugation of serum samples allows detection of hepatitis C virus RNA in patients with occult hepatitis C, " Journal of Virology, vol. 81, no. 14, pp. 7710-7715, 2007.
50. T. N. Q. Pham, C. S. Coffin, N. D. Churchill, S. J. Urbanski, S. S. Lee, and T. I. Michalak, "Hepatitis C virus persistence after sustained virological response to antiviral therapy in patients with or without past exposure to hepatitis B virus, " Journal of Viral Hepatitis, vol. 19, no. 2, pp. 103-111, 2012.
51. J. T. Blackard, N. Kemmer, and K. E. Sherman, "Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences, " Hepatology, vol. 44, no. 1, pp. 15-22, 2006.
52. V. Falcón, N. Acosta-Rivero, M. Shibayama et al., "Evidences of hepatitis C virus replication in hepatocytes and peripheral blood mononuclear cells from patients negative for viral RNA in serum, " American Journal of InfectiousDiseases, vol. 1, pp. 34-42, 2005.
53. I. Castillo, J. Bartolomé, J. A. Quiroga, G. Barril, and V. Carreño, "Diagnosis of occult hepatitis C without the need for a liver biopsy, " Journal ofMedical Virology, vol. 82, no. 9, pp. 1554-1559, 2010.
54. A. G. Muazzam, S. Qureshi, A. Mansoor et al., "Occult HCV or delayed viral clearance from lymphocytes of Chronic HCV genotype 3 patients after interferon therapy, " Genetic Vaccines andTherapy, vol. 9, no. 1, article 14, 2011.
55. P. B. Sugden, B. Cameron, R. Bull, P. A. White, and A. R. Lloyd, "Occult infection with hepatitis C virus: friend or foe, " Immunology and Cell Biology, vol. 90, no. 8, pp. 763-773, 2012.
56. P. B. Sugden, T. N. Q. Pham, S. Ratnarajah et al., "Rare occurrence of occult hepatitis C virus in apparently uninfected injecting drug users: A two-centre, masked, case-control study, " Journal of Viral Hepatitis, vol. 20, no. 10, pp. 725-728, 2013.
57. F. Ansaldi, B. Bruzzone, S. Salmaso et al., "Different seroprevalence and molecular epidemiology patterns of hepatitis C virus infection in Italy, " Journal of MedicalVirology, vol. 76, no. 3, pp. 327-332, 2005.
58. P. M. Kopko and P. V. Holland, "Universal leukocyte reduction, " Current Opinion in Hematology, vol. 7, no. 6, pp. 397-401, 2000.
59. L. De Marco, P. Manzini, M. Trevisan et al., "Prevalence and follow-up of occult HCV infection in an Italian population free of clinically detectable infectious liver disease, " PLoS ONE, vol. 7, no. 8, Article ID e43541, 2012.
60. 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, pp. 2248-2250, 2008.
61. I. Castillo, J. Bartolomé, J. A. Quiroga, G. Barril, and V. Carreño, "Long-term virological follow up of patients with occult hepatitis C virus infection, " Liver International, vol. 31, no. 10, pp. 1519-1524, 2011.
62. F. Bokharaei-Salim, H. Keyvani, S. H. R. Monavari et al., "Occult hepatitis C virus infection in Iranian patients with cryptogenicliver disease, " Journal ofMedical Virology, vol. 83, no. 6, pp. 989-995, 2011.
63. 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.
64. J. M. Cruzado, T. Casanovas-Taltavull, J. Torras, C. Baliellas, S. Gil-Vernet, and J. M. Grinyó, "Pretransplant interferon prevents hepatitis C virus-associated glomerulonephritis in renal allografts by HCV-RNA clearance, " The American Journal of Transplantation, vol. 3, no. 3, pp. 357-360, 2003.
65. S. Baid-Agrawal, R. Schindler, P. Reinke et al., "Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients, " Journal of Hepatology, vol. 60, no. 5, pp. 928-933, 2014.
66. P. Halfon, M. Martinot-Peignoux, and P. Cacoub, "The myth of occult hepatitis C infection, " Hepatology, vol. 50, no. 5, article 1675, 2009.
67. N. Coppola, M. Pisaturo, S. Guastafierro et al., "Absence of occult hepatitis C virus infection in patients under immunosupressive therapy for oncohematological diseases, " Hepatology, vol. 54, no. 4, pp. 1487-1489, 2011.
68. F. Nicot, N. Kamar, B. Mariamé, L. Rostaing, C. Pasquier, and J. Izopet, "No evidence of occult hepatitis C virus (HCV) infection in serum of HCV antibody-positive HCV RNA-negative kidney-transplant patients, " Transplant International, vol. 23, no. 6, pp. 594-601, 2010.
69. L. Richiardi, L. de Marco, A. Gillio-Tos et al., "Persistent infection by HCV and EBV in peripheral blood mononuclear cells and risk of non-Hodgkin's lymphoma, " Cancer Epidemiology, vol. 34, no. 6, pp. 709-712, 2010.
70. M. Casato, D. Lilli, G. Donato et al., "Occult hepatitis C virus infection in type II mixed cryoglobulinaemia, " Journal of Viral Hepatitis, vol. 10, no. 6, pp. 455-459, 2003.
71. C. Giannini, F. Giannelli, and A. L. Zignego, "Association between mixed cryogtobulinemia, translocation (14;18), and persistence of occult HCV lymphoid infection after treatment, " Hepatology, vol. 43, no. 5, pp. 1166-1167, 2006.
72. S. S. Youssef, A. S. Nasr, T. El Zanaty, R. S. El Rawi, and M. M. Mattar, "Prevalence of occult hepatitis C virus in Egyptian patients with chronic lymphoproliferative disorders, " Hepatitis Research and Treatment, vol. 2012, Article ID 429784, 6 pages, 2012.
73. M. Farahani, F. Bokharaei-Salim, M. Ghane, A. Basi, P. Meysami, and H. Keyvani, "Prevalence of occult hepatitis C virus infection in Iranian patients with lymphoproliferative disorders, " Journal of Medical Virology, vol. 85, no. 2, pp. 235-240, 2013.
74. I. Castillo, J. Martinez-Ara, T. Olea et al., "High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies, " Kidney International, vol. 86, pp. 619-624, 2014.
75. J. D. Scott and D. R. Gretch, "Molecular diagnostics of hepatitis C virus infection: A systematic review, " Journal of the American Medical Association, vol. 297, no. 7, pp. 724-732, 2007.
76. E. Kisiel, M. Radkowski, A. Pawelczyk et al., "Seronegative hepatitis C virus infection in patients with lymphoproliferative disorders, " Journal of Viral Hepatitis, vol. 21, no. 6, pp. 424-429, 2014.
77. J. A. Quiroga, S. Llorente, I. Castillo, E. Rodrguez-Iñigo, M. Pardo, and V. Carreño, "Cellular immune responses associated with occult hepatitis C virus infection of the liver, " Journal of Virology, vol. 80, no. 22, pp. 10972-10979, 2006.
78. V. Carreño, J. Bartolomé, I. Castillo, and J. A. Quiroga, "Occult hepatitis B virus and hepatitis C virus infections, " Reviews in Medical Virology, vol. 18, no. 3, pp. 139-157, 2008.
79. M. C. Roque-Cuéllar, B. Sánchez, J. R. Garca-Lozano et al., "Hepatitis C virus-specific cellular immune responses in sustained virological responders with viral persistence in peripheral blood mononuclear cells, " Liver International, vol. 34, no. 6, pp. e80-e88, 2014.
80. Y. S. Choi, J. E. Lee, S. J. Nam et al., "Two distinct functional patterns of hepatitis C Virus (HCV)-specific T cell responses in seronegative, aviremic patients, " PLoS ONE, vol. 8, no. 4, Article ID e62319, 2013.
81. H. R. Rosen, "Emerging concepts in immunity to hepatitis C virus infection, " Journal of Clinical Investigation, vol. 123, no. 10, pp. 4121-4130, 2013.
82. A. Grakoui, N. H. Shoukry, D. J. Woollard et al., "HCV persistence andimmune evasion in the absence ofmemory T cell help, " Science, vol. 302, no. 5645, pp. 659-662, 2003.
83. N. H. Shoukry, A. Grakoui, M. Houghton et al., "Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection, " Journal of Experimental Medicine, vol. 197, no. 12, pp. 1645-1655, 2003.
84. A. Y. Kim, T. Kuntzen, J. Timm et al., "Spontaneous control of HCV is associated with expression of HLA-B∗57 and preservation of targeted epitopes, " Gastroenterology, vol. 140, no. 2, pp. 686-696, 2011.
85. P. A. Knolle and R. Thimme, "Hepatic immune regulation and its involvement in viral hepatitis infection, " Gastroenterology, vol. 146, no. 5, pp. 1193-1207, 2014.
86. Y. Z. Gad, N. Mouas, A. Abdel-Aziz, N. Abousmra, and M. Elhadidy, "Distinct immunoregulatory cytokine pattern in Egyptian patients with occult Hepatitis C infection and unexplained persistently elevated liver transaminases, " Asian Journal of Transfusion Science, vol. 6, no. 1, pp. 24-28, 2012.
87. N. Mousa, W. Eldars, H. Eldegla et al., "Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection, " International Journal of Immunopathology and Pharmacology, vol. 27, no. 1, pp. 87-96, 2014.
88. J. K. Flynn, G. J. Dore, M. Hellard et al., "Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment, " Journal of Gastroenterology and Hepatology, vol. 28, no. 11, pp. 1770-1781, 2013.
89. L. Zhang, C. Q. Hao, L. Miao, and X. Dou, "Role of Th1/Th2 cytokines in serum on the pathogenesis of chronic hepatitis C and the outcome of interferon therapy, " Genetics and Molecular Research, vol. 13, no. 4, pp. 9747-9755, 2014.
90. J. J. Feld, J. Grebely, G. V. Matthews et al., "Plasma interferongamma-inducible protein-10 levels are associated with early, but not sustained virological response during treatment of acute or early chronic HCV infection, " PLoS ONE, vol. 8, no. 11, Article ID e80003, 2013.
91. V. Natarajan, S. Kottilil, A. Hazen et al., "HCV in peripheral blood mononuclear cells are predominantly carried on the surface of cells in HIV/HCV co-infected individuals, " Journal of Medical Virology, vol. 82, no. 12, pp. 2032-2037, 2010.
92. K. Fujiwara, R. D. Allison, R. Y. Wang et al., "Investigation of residual hepatitis C virus in presumed recovered subjects, " Hepatology, vol. 57, no. 2, pp. 483-491, 2013.
93. T. Laskus, M. Radkowski, A. Piasek et al., "Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes, " Journal of Infectious Diseases, vol. 181, no. 2, pp. 442-448, 2000.
94. S. Ramirez, S. Perez-Del-Pulgar, J. A. Carrion et al., "Hepatitis C virus compartmentalization and infection recurrence after liver transplantation, "American Journal of Transplantation, vol. 9, no. 7, pp. 1591-1601, 2009.
95. S. V. Kotenko, "IFN-s, " Current Opinion in Immunology, vol. 23, no. 5, pp. 583-590, 2011.
96. J. Vera-Otarola, M. I. Barra, U. León et al., "Hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cells of treatment näve chronically infected patients, " Journal ofViral Hepatitis, vol. 16, no. 9, pp. 633-643, 2009.
97. P. K. Chandra, L. Bao, K. Song et al., "HCV infection selectively impairs type i but not type III IFN signaling, " American Journal of Pathology, vol. 184, no. 1, pp. 214-229, 2014.
98. J. Angulo, K. Pino, C. Pavez et al., "Genetic variations in host IL28B links to the detection of peripheral blood mononuclear cells-associated hepatitis C virus RNA in chronically infected patients, " Journal of Viral Hepatitis, vol. 20, no. 4, pp. 263-272, 2013.
99. M. T. Dill, F. H. T. Duong, J. E. Vogt et al., "Interferoninduced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C, " Gastroenterology, vol. 140, no. 3, pp. 1021-1031, 2011.
100. S. Marukian, L. Andrus, T. P. Sheahan et al., "Hepatitis C virus induces interferon-lambda and interferon-stimulated genes in primary liver cultures, " Hepatology, vol. 54, no. 6, pp. 1913-1923, 2011.
101. O. Bauhofer, A. Ruggieri, B. Schmid, P. Schirmacher, and R. Bartenschlager, "Persistence of HCV in quiescent hepatic cells under conditions of an interferon-induced antiviral response, " Gastroenterology, vol. 143, no. 2, pp. 429-438, 2012.
102. A. Amanzada, A. Goralczyk, F. Moriconi et al., "Ultra-rapid virological response, young age, low-GT/ALT-ratio, and absence of steatosis identify a subgroup of HCV genotype 3 patients who achieve SVR with IFN-2a monotherapy, " Digestive Diseases and Sciences, vol. 56, no. 11, pp. 3296-3304, 2011.
103. S. S. Youssef, A. M. Abd El-Aal, A. Saad, M. Hassan Omran, T. El Zanaty, and S. M. Seif, "Impact of IL12B gene rs 3212227 polymorphism on fibrosis, liver inflammation, and response to treatment in genotype 4 Egyptian hepatitis C patients, " Disease Markers, vol. 35, no. 5, pp. 431-437, 2013.
104. F. Bellanti, G. Vendemiale, E. Altomare, and G. Serviddio, "The impact of interferon lambda 3 gene polymorphism on natural course and treatment of hepatitisC, "Clinical andDevelopmental Immunology, vol. 2012, Article ID 849373, 9 pages, 2012.
105. K. D. Ibarra, M. K. Jain, and J. K. Pfeiffer, "Host-based ribavirin resistance influences hepatitis C virus replication and treatment response, " Journal of Virology, vol. 85, no. 14, pp. 7273-7283, 2011.
106. R. M. Zinkernagel, "Immunology taught by viruses, " Science, vol. 271, no. 5246, pp. 173-178, 1996.
107. R. M. Zinkernagel, M. F. Bachmann, T. M. Kündig, S. Oehen, H. Pirchet, and H. Hengartner, "On immunological memory, " Annual Review of Immunology, vol. 14, no. 1, pp. 333-367, 1996.
108. R. M. Zinkernagel, S. Ehl, P. Aichele, S. Oehen, T. Kündig, and H. Hengartner, "Antigen localisation regulates immune responses in a dose-and time-dependent fashion: A geographical view of immune reactivity, " Immunological Reviews, vol. 156, pp. 199-209, 1997.
109. T. E. Starzl and R. M. Zinkernagel, "Antigen localization and migration inimmunity and tolerance, "TheNewEngland Journal of Medicine, vol. 339, no. 26, pp. 1905-1913, 1998.
110. J. T. Blackard, L. Smeaton, Y. Hiasa et al., "Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons, " Journal of Infectious Diseases, vol. 192, no. 2, pp. 258-265, 2005.
111. P. Baré, "Hepatitis C virus and peripheral blood mononuclear cell reservoirs Patricia Baré, " World Journal of Hepatology, vol. 1, no. 1, p. 67, 2009.
112. M. C. Roque-Cuéllar, B. Sánchez, J. R. Garca-Lozano, J. M. Praena-Fernández, A. Núñez-Roldán, and J. Aguilar-Reina, "Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients, " Journal of Viral Hepatitis, vol. 18, no. 10, pp. e541-e549, 2011.
113. H. Keyvani, F. Bokharaei-Salim, S. H. Monavari et al., "Occult hepatitis C virus infection in candidates for liver transplant with cryptogenic cirrhosis, " Hepatitis Monthly, vol. 13, no. 8, Article ID e11290, 2013.
114. P. Dzekova Vidimliski, I. Nikolov, N. Matevska Geshkovska, A. Dimovski, L. Rostaing, and A. Sikole, "Occult hepatitis C virus infection: still remains a controversy, " Journal of Medical Virology, vol. 86, no. 9, pp. 1491-1498, 2014.
115. L. Gatserelia, L. Sharvadze, M. Karchava et al., "Occurrence of occultHCVinfection amongHIV infected patients inGeorgia, " Georgian Medical News, no. 226, pp. 37-41, 2014.
116. T. Laskus, E. A. Operskalski, M. Radkowski et al., "Negativestrand hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells from anti-HCV-positive/HIV-infected women, " The Journal of Infectious Diseases, vol. 195, no. 1, pp. 124-133, 2007.
117. A. Paweczyk, N. Kubisa, J. Jaboń;ska et al., "Detection of hepatitis C virus (HCV) negative strand RNA and NS3 protein in peripheral blood mononuclear cells (PBMC): CD3+, CD14+ and CD19+, " Virology Journal, vol. 10, article 46, 2013.
118. M. Z. Rahman, D. S. Ahmed, H. Masud et al., "Sustained virological response after treatment in patients with chronic hepatitis C infection-afive year followup, " BangladeshMedical Research Council Bulletin, vol. 39, no. 1, pp. 11-13, 2013.
119. A. Sood, V. Midha, V. Mehta et al., "Howsustained is sustained viral response in patients with hepatitis C virus infection?" Indian Journal of Gastroenterology, vol. 29, no. 3, pp. 112-115, 2010.
120. K. Rutter, H. Hofer, S. Beinhardt et al., "Durability of SVR in chronic hepatitis C patients treated with peginterferon-2a/ribavirin in combination with a direct-acting anti-viral, " Alimentary Pharmacology and Therapeutics, vol. 38, no. 2, pp. 118-123, 2013.
121. C. E. Gordon, K. Uhlig, C. H. Schmid, A. S. Levey, and J. B. Wong, "Long-term viral negativity after Interferon for chronic hepatitis C virus infection in hemodialysis, " Clinical Journal of the American Society of Nephrology, vol. 6, no. 9, pp. 2226-2234, 2011.
122. E. G. Giannini, M. Basso, V. Savarino, and A. Picciotto, "Sustained virological response to pegylated interferon and ribavirin is maintained during longterm follow up of chronic hepatitis C patients, " Alimentary Pharmacology &Therapeutics, vol. 31, pp. 502-508, 2010.
123. F. M. Cortés-Mancera, J. C. Restrepo, G. Osorio, S. Hoyos, G. Correa, and M. C. Navas, "Occult hepatitis C virus infection in a re-transplanted patientwith liver failure of unknown etiology, " Revista Colombiana de Gastroenterologia, vol. 25, no. 1, pp. 76-85, 2010.
124. J. A. Quiroga, I. Castillo, M. Pardo, E. Rodrguez-Iñigo, and V. Carreño, "Combined hepatitis C virus (HCV) antigen-antibody detection assay does not improve diagnosis for seronegative individuals with occult HCV infection, " Journal of Clinical Microbiology, vol. 44, no. 12, pp. 4559-4560, 2006.
125. M. Comar, G. Dal Molin, P. D'Agaro, S. L. Crocè, C. Tiribelli, and C. Campello, "HBV, HCV, and TTV detection by in situ polymerase chain reaction could reveal occult infection in hepatocellular carcinoma: comparison with blood markers, " Journal of Clinical Pathology, vol. 59, no. 5, pp. 526-529, 2006.
126. J. A. Quiroga, S. Llorente, I. Castillo et al., "Tracking intrafamilial spread of serologically silent occult HCV infection through humoral and cellular HCV-specific responses, " Journal of Hepatology, vol. 50, supplement 1, p. S149, 2009.
127. F. Fabrizi and P. Martin, "Occult hepatitis C virus infection in hemodialysis, " Journal of the American Society of Nephrology, vol. 19, no. 12, pp. 2248-2250, 2008.
128. H. Lerat and F. B. Hollinger, "Hepatitis C virus (HCV) occult infection or occult HCV RNA detection?" Journal of Infectious Diseases, vol. 189, no. 1, pp. 3-6, 2004.
129. J. W. Ward, "The hidden epidemic of hepatitis C virus infection in theUnited States: occult transmission and burden of disease, " Topics in Antiviral Medicine, vol. 21, no. 1, pp. 15-19, 2013.
130. H. S. Dhaliwal and R. V. Nampoothiri, "Daclatasvir plus sofosbuvir for HCV infection, " The New England Journal of Medicine, vol. 370, no. 16, pp. 1560-1561, 2014.
131. C. Berasain, M. Betés, A. Panizo et al., "Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology, " Gut, vol. 47, no. 3, pp. 429-435, 2000.
132. M. P. Manns, P. J. Pockros, G. Norkrans et al., "Long-term clearance of hepatitis C virus following interferon-2b or peginterferon-2b, alone or in combination with ribavirin, " Journal of Viral Hepatitis, vol. 20, no. 8, pp. 524-529, 2013.
133. Roche Diagnostics, COBAS AmpliPrep/COBAS TaqMan HCV Test, http://www. roche-diagnostics. us.
134. Abbott Molecular, http://www. abbottmolecular. com/.
135. BayerMaterialScience, 2014, http://www. bayermaterialsciencenafta. com/.
136. G. Li, K. Li, A. S. Lea et al., "In situ hybridization for the detection of hepatitis C virus RNA in human liver tissue, " Journal of Viral Hepatitis, vol. 20, no. 3, pp. 183-192, 2013.