Occult hepatitis C: How convincing are the current data?

Hepatology

Volumn 49, Issue 2, 2009, Pages 665-675

  Welker, Martin Walter ^a   Zeuzem, Stefan ^a  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

PEGINTERFERON; PEGINTERFERON ALPHA; RIBAVIRIN; VIRUS DNA; VIRUS RNA; ALPHA INTERFERON; ANTIVIRUS AGENT;

ADAPTIVE IMMUNITY; CRYOGLOBULINEMIA; DISEASE CLASSIFICATION; DRUG RESPONSE; HEPATITIS C; HEPATITIS C VIRUS; HISTOPATHOLOGY; HUMAN; IDIOPATHIC DISEASE; IMMUNE RESPONSE; IMMUNOCOMPROMISED PATIENT; LIVER CIRRHOSIS; LIVER DISEASE; NONHUMAN; OCCULT HEPATITIS C; PRIORITY JOURNAL; RECURRENCE RISK; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; RNA ANALYSIS; SENSITIVITY ANALYSIS; VIRUS DETECTION; VIRUS REPLICATION; BLOOD; CLASSIFICATION; GENETICS; IMMUNE DEFICIENCY; PATHOLOGY; RECURRENT DISEASE;

ANTIVIRAL AGENTS; HEPACIVIRUS; HEPATITIS C; HUMANS; IMMUNOCOMPROMISED HOST; INTERFERON-ALPHA; RECURRENCE; RNA, VIRAL;

EID: 61949417110     PISSN: 02709139     EISSN: None     Source Type: Journal    
DOI: 10.1002/hep.22706     Document Type: Review

References (163)

1. Bartolome J, Lopez-Alcorocho JM, Castillo I, Rodriguez-Inigo E, Quiroga JA, Palacios R, et al. Ultracentrifugation of serum samples allows detection of hepatitis C virus RNA in patients with occult hepatitis C. J Virol 2007;81:7710-7715.
2. Castillo I, Rodriguez-Inigo E, Barril G, Arenas D, Espinosa M, Garcia-Valdecasas J, et al. Occult HCV infection in hemodialysis patients [Abstract]. HEPATOLOGY 2005;42(Suppl. 1):437A.
3. Radkowski M, Gallegos-Orozco JF, Jablonska J, Colby TV, Walewska-Zielecka B, Kubicka J, et al. Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. HEPATOLOGY 2005;41:106-114.
4. Comar M, Dal Molin G, D'Agaro P, Croce SL, Tiribelli C, Campello C. HBV, HCV, and TTV detection by in situ polymerase chain reaction could reveal occult infection in hepatocellular carcinoma: Comparison with blood markers. J Clin Pathol 2006;59:526-529.
5. Radkowski M, Horban A, Gallegos-Orozco JF, Pawelczyk A, Jablonska J, Wilkinson J, et al. Evidence for viral persistence in patients who test positive for anti-hepatitis C virus antibodies and have normal alanine aminotransferase levels. J Infect Dis 2005;191:1730-1733.
6. Carreno V, Castillo I, Bartolome J, Rodriguez-Inigo E, Ortiz-Movilla N, de Lucas S, et al. Comparison of hepatitis C virus RNA detection in plasma, whole blood and peripheral blood mononuclear cells of patients with occult hepatitis C virus infection. J Clin Virol 2004;31:312-313.
7. Carreno V, Pardo M, Lopez-Alcorocho JM, Rodriguez-Inigo E, Bartolome J, Castillo I. Detection of hepatitis C virus (HCV) RNA in the liver of healthy, anti-HCV antibody-positive, serumHCVRNA-negative patients with normal alanine aminotransferase levels. J Infect Dis 2006; 194:53-60.
8. Castillo I, Rodriguez-Inigo E, Lopez-Alcorocho JM, Pardo M, Bartolome J, Carreno V. Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment. Clin Infect Dis 2006;43: 1277-1283.
9. Castillo I, Rodriguez-Inigo E, Bartolome J, de Lucas S, Ortiz-Movilla N, Lopez-Alcorocho JM, et al. Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection. Gut 2005;54:682-685.
10. Castillo I, Pardo M, Bartolome J, Ortiz-Movilla N, Rodriguez-Inigo E, de Lucas S, et al. Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown. J Infect Dis 2004;189:7-14.
11. Castillo I, Rodriguez-Inigo E, Lopez-Alcorocho JM, Bartolome J, Pardo M, Carreno V. 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. J Med Virol 2007;79:236-241.
12. Pardo M, Lopez-Alcorocho JM, Rodriguez-Inigo E, Castillo I, Carreno V. Comparative study between occult hepatitis C virus infection and chronic hepatitis C. J Viral Hepat 2007;14:36-40.
13. Pardo M, Lopez-Alcorocho JM, Castillo I, Rodriguez-Inigo E, Perez-Mota A, Carreno V. Effect of anti-viral therapy for occult hepatitis C virus infection. Aliment Pharmacol Ther 2006;23:1153-1159.
14. Quiroga JA, Llorente S, Castillo I, Rodriguez-Inigo E, Lopez-Alcorocho JM, Pardo M, et al. Virus-specific T-cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection. J Med Virol 2006;78:1190-1197.
15. Carreno V. Occult hepatitis C virus infection: A new form of hepatitis C. World J Gastroenterol 2006;12:6922-6925.
16. Bartenschlager R, Lohmann V. Replication of hepatitis C virus. J Gen Virol 2000;81:1631-1648.
17. Lerat H, Berby F, Trabaud MA, Vidalin O, Major M, Trepo C, et al. Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells. J Clin Invest 1996;97:845-851.
18. Laskus T, Radkowski M, Bednarska A, Wilkinson J, Adair D, Nowicki M, et al. Detection and analysis of hepatitis C virus sequences in cerebrospinal fluid. J Virol 2002;76:10064-10068.
19. Vargas HE, Laskus T, Radkowski M, Wilkinson J, Balan V, Douglas DD, et al. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation. Liver Transpl 2002;8: 1014-1019.
20. Radkowski M, Kubicka J, Kisiel E, Cianciara J, Nowicki M, Rakela J, et al. Detection of active hepatitis C virus and hepatitis G virus/GB virus C replication in bone marrow in human subjects. Blood 2000;95:3986-3989.
21. Okuda M, Hino K, Korenaga M, Yamaguchi Y, Katoh Y, Okita K. Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver. HEPATOLOGY 1999;29:217-222.
22. Willems M, Peerlinck K, Moshage H, Deleu I, Van den EC, Vermylen J, et al. Hepatitis C virus-RNAs in plasma and in peripheral blood mononuclear cells of hemophiliacs with chronic hepatitis C: Evidence for viral replication in peripheral blood mononuclear cells. J Med Virol 1994;42: 272-278.
23. Radkowski M, Wilkinson J, Nowicki M, Adair D, Vargas H, Ingui C, et al. Search for hepatitis C virus negative-strand RNA sequences and analysis of viral sequences in the central nervous system: Evidence of replication. J Virol 2002;76:600-608.
24. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998;282:103-107.
25. Herrmann E, Neumann AU, Schmidt JM, Zeuzem S. Hepatitis C virus kinetics. Antivir Ther 2000;5:85-90.
26. Lee WM, Polson JE, Carney DS, Sahin B, Gale M Jr. Reemergence of hepatitis C virus after 8.5 years in a patient with hypogammaglobulinemia: Evidence for an occult viral reservoir. J Infect Dis 2005;192:1088-1092.
27. Pham TN, MacParland SA, Mulrooney PM, Cooksley H, Naoumov NV, Michalak TI. Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C. J Virol 2004;78:5867-5874.
28. Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Castelnau C, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 1997;127:875-881.
29. Pham TN, Michalak TI. Occult hepatits C virus persistence: identification and characteristics. MLO Med Lab Obs 2006;38:20-22.
30. Pham TN, Mulrooney-Cousins PM, Mercer SE, MacParland SA, Inglot M, Zalewska M, et al. Antagonistic expression of hepatitis C virus and alpha interferon in lymphoid cells during persistent occult infection. J Viral Hepat 2007;14:537-548.
31. Diodati G, Pontisso P, Bonetti P, Stenico D, Noventa F, Alberti A, et al. Cryptogenic chronic liver disease and serum or liver hepatitis B virus markers. Their possible correlations and etiologic significance. Digestion 1988;39:251-256.
32. Chemin I, Zoulim F, Merle P, Arkhis A, Chevallier M, Kay A, et al. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol 2001;34:447-454.
33. Berasain C, Betes M, Panizo A, Ruiz J, Herrero JI, Civeira MP, et al. Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology. Gut 2000;47:429-435.
34. Geller SA, Nichols WS, Rojter SE, Chan RC, Petrovic LM, Vierling JM, Makowka L. Hepatitis C virus is not recoverable from liver tissue in cryptogenic cirrhosis: Failure to identify hepatitis C virus-RNA using reverse transcription-mediated polymerase chain reaction. Hum Pathol 1996;27:1161-1165.
35. Halfon P, Bourliere M, Ouzan D, Sene D, Saadoun D, Khiri H, et al. Occult hepatitis C virus infection revisited with ultrasensitive real-time PCR assay. J Clin Microbiol 2008;46:2106-2108.
36. Barril G, Castillo I, Arenas MD, Espinosa M, Garcia-Valdecasas J, Garcia-Fernandez N, et al. Occult hepatitis C virus infection among hemodialysis patients. J Am Soc Nephrol 2008; doi:10.1681/ASN.2008030293.
37. Tagiuri NI, McClure P, Ryder SD, Irving WL. Occult hepatitis C infection in patients with histological hepatitis and negative serum PCR for HCV [Abstract]. J Hepatol 2008;44(S2):S157.
38. Verslype C, Nevens F, Sinelli N, Clarysse C, Pirenne J, Depla E, et al. Hepatic immunohistochemical staining with a monoclonal antibody against HCV-E2 to evaluate antiviral therapy and reinfection of liver grafts in hepatitis C viral infection. J Hepatol 2003;38:208-214.
39. Schmidt WN, Wu P, Cederna J, Mitros FA, Labrecque DR, Stapleton JT. Surreptitious hepatitis C virus (HCV) infection detected in the majority of patients with cryptogenic chronic hepatitis and negative HCV antibody tests. J Infect Dis 1997;176:27-33.
40. Kodali VP, Gordon SC, Silverman AL, McCray DG. Cryptogenic liver disease in the United States: Further evidence for non-A, non-B, and non-C hepatitis. Am J Gastroenterol 1994;89:1836-1839.
41. Lerat H, Hollinger FB. Hepatitis C virus (HCV) occult infection or occult HCV RNA detection? J Infect Dis 2004;189:3-6.
42. Zheng X, Pang M, Chan A, Roberto A, Warner D, Yen-Lieberman B. Direct comparison of hepatitis C virus genotypes tested by INNO-LiPA HCV II and TRUGENE HCV genotyping methods. J Clin Virol 2003; 28:214-216.
43. Dries V, Schirmacher P, Dienes HP, Gerken G, Bartenschlager R. Serum versus intrahepatic HCV RNA and liver histology. HEPATOLOGY 2002; 35:1552-1553.
44. Dahari H, Major M, Zhang X, Mihalik K, Rice CM, Perelson AS, et al. Mathematical modeling of primary hepatitis C infection: Noncytolytic clearance and early blockage of virion production. Gastroenterology 2005;128:1056-1066.
45. Zeuzem S, Schmidt JM, Lee JH, Ruster B, Roth WK. Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo. HEPATOLOGY 1996;23:366-371.
46. Zeuzem S, Schmidt JM, Lee JH, von Wagner M, Teuber G, Roth WK. Hepatitis C virus dynamics in vivo: Effect of ribavirin and interferon alfa on viral turnover. HEPATOLOGY 1998;28:245-252.
47. Barrett S, Kieran N, Ryan E, O'keane JC, Crowe J. Intrahepatic hepatitis C viral RNA status of serum polymerase chain reaction-negative individuals with histological changes on liver biopsy. HEPATOLOGY 2001;33: 1496-1502.
48. McHutchison JG, Poynard T, Esteban-Mur R, Davis GL, Goodman ZD, Harvey J, et al. Hepatic HCV RNA before and after treatment with interferon alone or combined with ribavirin. HEPATOLOGY 2002;35:688-693.
49. Bizollon T, Ahmed SN, Radenne S, Chevallier M, Chevallier P, Parvaz P, et al. Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C. virus recurrence. Gut 2003;52:283-287.
50. Bernardin F, Tobler L, Walsh I, Williams JD, Busch M, Delwart E. Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia. HEPATOLOGY 2008;47:1446-1452.
51. Dries V, von Both I, Müller M, Gerken G, Schirmacher P, Odenthal M, et al. Detection of hepatitis C virus in paraffin-embedded liver biopsies of patients negative for viral RNA in serum. HEPATOLOGY 1999;29:223-229.
52. Sugiyasu Y, Yuki N, Nagaoka T, Yamashiro M, Kawahara K, Iyoda K, et al. Histological improvement of chronic liver disease after spontaneous serum hepatitis C virus clearance. J Med Virol 2003;69:41-49.
53. Haydon GH, Jarvis LM, Blair CS, Simmonds P, Harrison DJ, Simpson KJ, et al. Clinical significance of intrahepatic hepatitis C virus levels in patients with chronic HCV infection. Gut 1998;42:570-575.
54. Pinarbasi B, Bozaci M, Akyuz F, Badur S, Demir K, Besisik F, et al. The presence of HCVRNA in the peripheral blood mononuclear cells of the individuals with isolated anti HCV positivity: Is HCV hiding out? [Abstract] J Hepatol 2008;48(S2):S222.
55. Veldt BJ, Saracco G, Boyer N, Camma C, Bellobuono A, Hopf U, et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Gut 2004;53:1504-1508.
56. Camma C, Giunta M, Pinzello G, Morabito A, Verderio P, Pagliaro L. Chronic hepatitis C and interferon alpha: Conventional and cumulative meta-analyses of randomized controlled trials. Am J Gastroenterol 1999; 94:581-595.
57. Wiegand J, Jackel E, Cornberg M, Hinrichsen H, Dietrich M, Kroeger J, et al. Long-term follow-up after successful interferon therapy of acute hepatitis C. HEPATOLOGY 2004;40:98-107.
58. Bare P, Massud I, Belmonte L, Corti M, Villafane M, Perez BR, et al. HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV-HIV co-infected haemophilic patients with undetectable HCV viraemia. Haemophilia 2003;9:598-604.
59. Pham TN, MacParland SA, Coffin CS, Lee SS, Bursey FR, Michalak TI. Mitogen-induced upregulation of hepatitis C virus expression in human lymphoid cells. J Gen Virol 2005;86:657-666.
60. Saleh MG, Tibbs CJ, Koskinas J, Pereira LM, Bomford AB, Portmann BC, et al. Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy. HEPATOLOGY 1994;20:1399-1404.
61. Qian C, Camps J, Maluenda MD, Civeira MP, Prieto J. Replication of hepatitis C virus in peripheral blood mononuclear cells. Effect of alpha-interferon therapy. J Hepatol 1992;16:380-383.
62. El-Raziky MS, El-Akel WA, Soliman MA, El-Kafrawy S, Abdel-Hamid M, Esmat G. HCV RNA in peripheral blood mononuclear cells (PBMNCS) of sustained virological responders to interferon based therapies: Is it a risk for relapse? [Abstract] HEPATOLOGY 2005;42(S1):431.
63. Gallegos JF, Rakela J, Rosati MJ, Vargas H, Balan V. Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C (CHC) with pegylated interferon and ribavirin [Abstract]. HEPATOLOGY 2005;42(S1):565.
64. Giannini C, Petrarca A, Arena U, Monti M, Solazzo V, Giannelli F, et al. Analysis of HCV persistence in patients with sustained virological response [Abstract]. J Hepatol 2006;44(S2):S6.
65. Caudai C, Padula MG, Bastianoni I, Valensin PE, Shyamala V, Han J, et al. Antibody testing and RT-PCR results in hepatitis C virus (HCV) infection: HCV-RNA detection in PBMC of plasma viremia-negative HCV-seropositive persons. Infection 1998;26:151-154.
66. Basaras M, de las Heras B, Garcia BM, Gallego L, Arrese E, Cisterna R. Detection of hepatitis C virus RNA in serum and peripheral blood mononuclear cells in patients with chronic hepatitis C treated with interferon alpha. Eur J Clin Microbiol Infect Dis 1996;15:887-890.
67. Berenguer M, Olaso V, Cordoba J, Gobernado M, Carrasco D, Berenguer J. Genome detection in liver and peripheral blood mononuclear cells: predictor factors of sustained response in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 1995;7:899-903.
68. Castillo I, Bartolome J, Navas S, Gonzalez S, Herrero M, Carreno V. Virological and biochemical long-term follow-up of patients with chronic hepatitis C treated with interferon. HEPATOLOGY 1994;19:1342-1346.
69. De Mitri MS, Morsica G, Chen CH, Mele L, Baccarini P, Chianese R, et al. Complete eradication of hepatitis C virus after interferon treatment for chronic hepatitis C. Ital J Gastroenterol Hepatol 1997;29:255-261.
70. Maylin S, Martinot-Peignoux M, Moucari R, Boyer N, Ripault MP, Cazals-Hatem D, et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology 2008;135:821-829.
71. Teramura K, Fukuda A, Kobayashi H, Yoshimoto S, Kawashima H, Ohsawa N. Virus elimination and histologic improvement in patients with chronic hepatitis C treated with interferon alpha. J Clin Gastroenterol 1997;25:346-351.
72. Romeo R, Pol S, Berthelot P, Brechot C. Eradication of hepatitis C virus RNA after alpha-interferon therapy. Ann Intern Med 1994;121:276-277.
73. Gil B, Qian C, Riezu-Boj JI, Civeira MP, Prieto J. Hepatic and extrahepatic HCV RNA strands in chronic hepatitis C: Different patterns of response to interferon treatment. HEPATOLOGY 1993;18:1050-1054.
74. Kamar N, Toupance O, Buchler M, Sandres-Saune K, Izopet J, Durand D, et al. Evidence that clearance of hepatitis C virus RNA after alpha-interferon therapy in dialysis patients is sustained after renal transplantation. J Am Soc Nephrol 2003;14:2092-2098.
75. Kusaka S, Okusa T, Araki A, Fujiki K, Takashimizu I, Okayasu I, et al. Prediction of relapses after interferon-alpha therapy by hepatitis C virus RNA in peripheral blood mononuclear cells. J Med Virol 1995;46:265-268.
76. Martinot-Peignoux M, Maylin S, Boyer N, Cardoso AC, Ripault MP, Giuily N, et al. Sustained virological response is associated with eradication of hepatitis C virus and decrease in anti-HCV titer in patients treated for chronic hepatitis C [Abstract]. J Hepatol 2008;48(S2):S302.
77. Garcia-Bengoechea M, Basaras M, Barrio J, Arrese E, Montalvo II, Arenas JI, et al. Late disappearance of hepatitis C virus RNA from peripheral blood mononuclear cells in patients with chronic hepatitis C in sustained response after alpha-interferon therapy. Am J Gastroenterol 1999;94: 1902-1905.
78. McHutchison JG, Shiffman ML, Gordon SC, Lindsay KL, Morgan T, Norkrans G, et al. Sustained virologic response (SVR) to interferon alpha-2b +/- ribavirin therapy at 6 months reliably predicts long-term clearance of HCV at 5-year follow-up [Abstract]. J Hepatol 2006;44(S2): S275.
79. Sarrazin C, Hendricks DA, Sedarati F, Zeuzem S. Assessment, by transcription-mediated amplification, of virologic response in patients with chronic hepatitis C virus treated with peginterferon alpha-2a. J Clin Microbiol 2001;39:2850-2855.
80. Sawyer LK, Leung K, Friesenhahn M, Duey D, McMorrow M, Eguchi B. Clinical laboratory evaluation of a new sensitive and specific assay for qualitative detection of hepatitis C virus RNA in clinical specimens [Abstract]. J Hepatol 2000;32(S2):116A.
81. Wedemeyer H, He XS, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, et al. Impaired effector function of hepatitis C virus specific CD8+ T cells in chronic hepatitis C virus infection. J Immunol 2002;169:3447-3458.
82. Rehermann B. Interaction between the hepatitis C virus and the immune system. Semin Liver Dis 2000;20:127-141.
83. Nascimbeni M, Mizukoshi E, Bosmann M, Major ME, Mihalik K, Rice CM, et al. Kinetics of CD4+ and CD8+ memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees. J Virol 2003;77:4781-4793.
84. Lechmann M, Ihlenfeldt HG, Braunschweiger I, Giers G, Jung G, Matz B, et al. T- and B-cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti-hepatitis C virus- positive blood donors without viremia. HEPATOLOGY 1996;24:790-795.
85. Takaki A, Wiese M, Maertens G, Depla E, Seifert U, Liebetrau A, et al. Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat Med 2000;6:578-582.
86. Grakoui A, Shoukry NH, Woollard DJ, Han JH, Hanson HL, Ghrayeb J, et al. HCV persistence and immune evasion in the absence of memory T cell help. Science 2003;302:659-662.
87. Shoukry NH, Grakoui A, Houghton M, Chien DY, Ghrayeb J, Reimann KA, et al. Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med 2003;197:1645-1655.
88. Gerlach JT, Diepolder HM, Jung MC, Gruener NH, Schraut WW, Zachoval R, et al. Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. Gastroenterology 1999;117:933-941.
89. Gruner NH, Gerlach TJ, Jung MC, Diepolder HM, Schirren CA, Schraut WW, et al. Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C. J Infect Dis 2000;181:1528-1536.
90. Diepolder HM, Zachoval R, Hoffmann RM, Wierenga EA, Santantonio T, Jung MC, et al. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 1995;346:1006-1007.
91. von Hahn T, Yoon JC, Alter H, Rice CM, Rehermann B, Balfe P, et al. Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 2007; 132:667-678.
92. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005;5:215-229.
93. Bronowicki JP, Vetter D, Uhl G, Hudziak H, Uhrlacher A, Vetter JM, et al. Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for exposure to HCV in HCV-seronegative spouses of HCV infected patients. J Infect Dis 1997;176:518-522.
94. Koziel MJ, Wong DK, Dudley D, Houghton M, Walker BD. Hepatitis C virus-specific cytolytic T lymphocyte and T helper cell responses in seronegative persons. J Infect Dis 1997;176:859-866.
95. Manns MP, Michel G. Detection of anti-GOR antibodies in HCV infection. In: JYN Lau, ed. Hepatitis C Protocols. Totowa, NJ: Humana Press; 1998:3-9.
96. Antonelli A, Ferri C, Galeazzi M, Giannitti C, Manno D, Mieli-Vergani G, et al. HCV infection: Pathogenesis, clinical manifestations and therapy. Clin Exp Rheumatol 2008;26:S39-S47.
97. El Serag HB, Hampel H, Yeh C, Rabeneck L. Extrahepatic manifestations of hepatitis C among United States male veterans. HEPATOLOGY 2002;36:1439-1445.
98. Quiroga JA, Castillo I, Bartolome J, Carreno V. Serum immunoglobulin G antibodies to the GOR autoepitope are present in patients with occult hepatitis C virus (HCV) infection despite lack of HCV-specific antibodies. Clin Vaccine Immunol 2007;14:1302-1306.
99. Yee LJ, Kelleher P, Goldin RD, Marshall S, Thomas HC, Alberti A, et al. Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance. J Viral Hepat 2004;11:459-464.
100. Casato M, Lilli D, Donato G, Granata M, Conti V, Del Giudice G, et al. Occult hepatitis C virus infection in type II mixed cryoglobulinaemia. J Viral Hepat 2003;10:455-459.
101. Giannini C, Giannelli F, Zignego AL. Association between mixed cryoglobulinemia, translocation (14;18), and persistence of occult HCV lymphoid infection after treatment. HEPATOLOGY 2006;43:1166-1167.
102. Thomson EC, Fleming VM, Main J, McClure M, Karayiannis P. Reactivation of hepatitis C in a patient with advanced human immunodeficiency virus infection [Abstract]. J Hepatol 2008;48(S2):S250.
103. Kim AY, Schulze zur Wiesch J, Kuntzen T, Timm J, Kaufmann DE, Duncan JE, et al. Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection. PLoS Med 2006;3:e492.
104. Melisko ME, Fox R, Venook A. Reactivation of hepatitis C virus after chemotherapy for colon cancer. Clin Oncol (R Coll Radiol) 2004;16: 204-205.
105. Zekri AR, Mohamed WS, Samra MA, Sherif GM, El Shehaby AM, El Sayed MH. Risk factors for cytomegalovirus, hepatitis B and C virus reactivation after bone marrow transplantation. Transpl Immunol 2004; 13:305-311.
106. Gholam PM, Taylor LE, DeLong AK, Lazarus TS, Cintron V, Mayer KH, et al. Occult HBV and HCV viremia in women at risk for and with HIV infection [Abstract]. HEPATOLOGY 2006;44(S1):696.
107. Rai RR, Mathur A, Mathur D, Udawat HP, Nepalia S, Nijhawan S, et al. Prevalence of occult hepatitis B & C in HIV patients infected through sexual transmission. Trop Gastroenterol 2007;28:19-23.
108. Thongsawat S, Maneekarn N, Kuniholm MH, Pantip C, Thungsuputi A, Lumlertkul D, et al. Occult hepatitis C virus infection during an outbreak in a hemodialysis unit in Thailand. J Med Virol 2008;80:808-815.
109. Feld JJ, Liang TJ. HCV persistence: Cure is still a four letter word. HEPATOLOGY 2005;41:23-25.
110. Esaki T, Suzuki N, Yokoyama K, Iwata K, Irie M, Anan A, et al. Hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV tests but positive liver tissue HCV RNA. Intern Med 2004;43:279-282.
111. Ware JE Jr, Bayliss MS, Mannocchia M, Davis GL. Health-related quality of life in chronic hepatitis C: Impact of disease and treatment response. The Interventional Therapy Group. HEPATOLOGY 1999;30:550-555.
112. Younossi Z, Kallman J, Kincaid J. The effects of HCV infection and management on health-related quality of life. HEPATOLOGY 2007;45: 806-816.
113. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002;122: 1303-1313.
114. Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, et al. Antiviral therapy for cirrhotic hepatitis C: Association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med 2005;142:105-114.
115. Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: A retrospective study. HEPATOLOGY 2007;45:579-587.
116. Veldt BJ, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, Zeuzem S, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 2007;147:677-684.
117. Buti M, San Miguel R, Brosa M, Cabases JM, Medina M, Angel CM, et al. Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C. J Hepatol 2005;42:639-645.
118. Moreno M, Perez-Alvarez R, Rodrigo L, Perez-Lopez R, Suarez-Leiva P. Long-term evolution of serum and liver viral markers in patients treated for chronic hepatitis C and sustained response. J Viral Hepat 2006;13: 28-33.
119. Reichard O, Glaumann H, Fryden A, Norkrans G, Schvarcz R, Sonnerborg A, et al. Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment. HEPATOLOGY 1995;21:918-922.
120. Chemello L, Cavalletto L, Casarin C, Bonetti P, Bernardinello E, Pontisso P, et al. Persistent hepatitis C viremia predicts late relapse after sustained response to interferon-alpha in chronic hepatitis C. TriVeneto Viral Hepatitis Group. Ann Intern Med 1996;124:1058-1060.
121. Vento S, Concia E, Ferraro T. Lack of sustained efficacy of interferon in patients with chronic hepatitis C. N Engl J Med 1996;334:1479-1480.
122. Camma C, Di Marco V, Lo Iacono O, Almasio P, Giunta M, Fuschi P, et al. Long-term course of interferon-treated chronic hepatitis C. J Hepatol 1998;28:531-537.
123. Larghi A, Tagger A, Crosignani A, Ribero ML, Bruno S, Portera G, et al. Clinical significance of hepatic HCV RNA in patients with chronic hepatitis C demonstrating long-term sustained response to interferon-alpha therapy. J Med Virol 1998;55:7-11.
124. Lau DT, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH. 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. HEPATOLOGY 1998;28:1121-1127.
125. Sim H, Yim C, Krajden M, Heathcote J. Durability of serological remission in chronic hepatitis C treated with interferon-alpha-2B. Am J Gastroenterol 1998;93:39-43.
126. Reichard O, Glaumann H, Fryden A, Norkrans G, Wejstal R, Weiland O. Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon. J Hepatol 1999;30:783-787.
127. Schvarcz R, Glaumann H, Reichard O, Weiland O. Histological and virological long-term outcome in patients treated with interferon alpha2b and ribavirin for chronic hepatitis C. J Viral Hepat 1999;6:237-242.
128. Collier JD, Adams PA, Feinman V, Ghent C, Witt-Sullivan H, Minuk G, et al. Long term follow-up of patients with chronic hepatitis C treated with interferon alpha. Can J Gastroenterol 2000;14(Suppl B):77B- 80B.
129. Bruno S, Battezzati PM, Bellati G, Manzin A, Maggioni M, Crosignani A, et al. Long-term beneficial effects in sustained responders to interferonalfa therapy for chronic hepatitis C. J Hepatol 2001;34:748-755.
130. Giannini E, Fasoli A, Botta F, Testa E, Romagnoli P, Ceppa P, et al. Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: A functional study. J Gastroenterol Hepatol 2001;16:399-405.
131. Dalgard O, Bjoro K, Hellum K, Myrvang B, Skaug K, Gutigard B, et al. Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up. Eur Addict Res 2002;8:45-49.
132. Adinolfi LE, Utili R, Tonziello A, Ruggiero G. Effects of alpha interferon induction plus ribavirin with or without amantadine in the treatment of interferon non-responsive chronic hepatitis C: A randomised trial. Gut 2003;52:701-705.
133. Mozer-Lisewska I, Sluzewski W, Ali YK, Figlerowicz M, Kowala-Piaskowska A. Virus genotype 1b and long-term response to interferon alpha monotherapy in children with chronic hepatitis C. Eur J Pediatr 2003; 162:755-759.
134. Toccaceli F, Laghi V, Capurso L, Koch M, Sereno S, Scuderi M. Longterm liver histology improvement in patients with chronic hepatitis C and sustained response to interferon. J Viral Hepat 2003;10:126-133.
135. Khokhar N. Late relapse in chronic hepatitis C after sustained viral response to interferon and ribavirin. J Gastroenterol Hepatol 2004;19:471-472.
136. Tsuda N, Yuki N, Mochizuki K, Nagaoka T, Yamashiro M, Omura M, et al. Long-term clinical and virological outcomes of chronic hepatitis C after successful interferon therapy. J Med Virol 2004;74:406-413.
137. Chavalitdhamrong D, Tanwandee T. Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment. World J Gastroenterol 2006;12:5532-5535.
138. Ciancio A, Smedile A, Giordanino C, Colletta C, Croce G, Pozzi M, et al. Long-term follow-up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: Are they really cured? Am J Gastroenterol 2006;101:1811-1816.
139. Desmond CP, Roberts SK, Dudley F, Mitchell J, Day C, Nguyen S, et al. Sustained virological response rates and durability of the response to interferon-based therapies in hepatitis C patients treated in the clinical setting. J Viral Hepat 2006;13:311-315.
140. Formann E, Steindl-Munda P, Hofer H, Jessner W, Bergholz U, Gurguta C, et al. Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy. Aliment Pharmacol Ther 2006;23:507-511.
141. Fytili P, Wang C, Schaffer S, Schulz S, Manns MP, Wedemeyer H. Detection of low amounts of HCV-RNA in the serum of sustained virological responders after antiviral therapy [Abstract]. HEPATOLOGY 2006; 44(S1):282.
142. Jeffrey GP, MacQuillan G, Chua F, Galhenage S, Bull J, Young E, et al. Successfull hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implantants [Abstract]. 2006; 44(S1):331.
143. Kim JH, Han KH, Lee KS, Park YN, Ahn SH, Chon CY, et al. Efficacy and long-term follow up of combination therapy with interferon alpha and ribavirin for chronic hepatitis C in Korea. Yonsei Med J 2006;47: 793-798.
144. Basso M, Torre F, Blanchi S, Delfino A, Picciotto A. Long-term virological follow-up of patients with chronic hepatitis C who obtained a sustained virological response after treatment with pegylated interferon and ribavirin [Abstract]. J Hepatol 2007;46(S1):S201.
145. Pradat P, Tillmann HL, Sauleda S, Braconier JH, Saracco G, Thursz M, et al. Long-term follow-up of the hepatitis C HENCORE cohort: Response to therapy and occurrence of liver-related complications. J Viral Hepat 2007;14:556-563.
146. Swain MG, Lai MY, Shiffman ML, Cooksley WGE, Abergel A, Lin A, et al. Durable sustained virological response after treatment with peginterferon α-2a (Pegasys(R)) alone or in combination with ribavirin (Copegus (R)): 5-year follow-up and the criteria of a cure [Abstract]. J Hepatol 2007;46(S1):S3.
147. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Abergel A, Lin A, et al. Sustained virological response (SVR) is durable after treatment with peginterferon alfa-2a (40 KD) (Pegasys(R)) alone or in combination with ribavirin (Copegus(R)): Results of an ongoing long-term follow-up study [Abstract]. HEPATOLOGY 2005;42(S1):646A..
148. Torres-Ibarra R, Cano-Dominguez C. Sustained virological response after more than three years of the end of treatment with conventional alpha-2b or pegylated alpha-2a interferon [Abstract]. J Hepatol 2007; 46(S1):S247.
149. Kelly D, Haber B, Gonzalez-Peralta RP, Murray KF, Jonas MM, Molleston JP, et al. Sustained virologic response to interferon alfa-2b plus ribavirin predicts long-term clearance of HCV in pediatric patients at 5 year follow-up [Abstract]. J Hepatol 2008;48(S2):298.
150. Manns M, Lindsay KL, Gordon SC, Pockros PJ, Haeussinger D, Hadziyiannis S, et al. Sustained virologic response after peginterferon alfa-2b and ribavirin treatment predicts long-term clearance of HCV at 5-year follow-up [Abstract]. J Hepatol 2008;48(S2):S300.
151. Martinot-Peignoux M, Maylin S, Boyer N, Cardoso AC, Ripault MP, Giuily N, et al. Sustained virological response is associated with eradication of hepatitis C virus and decrease in anti-HCV titer in patients treated for chronic hepatitis C. J Hepatol 2008;48(S2):S302.
152. Soriano V, Maida I, Nunez M, Garcia-Samaniego J, Barreiro P, Martin-Carbonero L, et al. Long-term follow-up of HIV-infected patients with chronic hepatitis C virus infection treated with interferon-based therapies. Antivir Ther 2004;9:987-992.
153. Posthouwer D, Yee TT, Makris M, Fischer K, Griffioen A, Van Veen JJ, et al. Antiviral therapy for chronic hepatitis C in patients with inherited bleeding disorders: An international, multicenter cohort study. J Thromb Haemost 2007;5:1624-1629.
154. Abdelmalek MF, Firpi RJ, Soldevila-Pico C, Reed AI, Hemming AW, Liu C, et al. Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C. Liver Transpl 2004;10: 199-207.
155. Bizollon T, Pradat P, Mabrut JY, Chevallier M, Adham M, Radenne S, et al. Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C. Am J Transplant 2005;5:1909-1913.
156. Mukherjee S. Fatal liver disease despite sustained eradication of recurrent hepatitis C virus requiring liver retransplantation. Transplantation 2006; 82:286-288.
157. Lilly L, Girgrha N, Therapondos G. Sustained virological response in patients successfully treated for recurrent hepatitis C following liver transplantation is highly durable [Abstract]. HEPATOLOGY 2007; 46(S1):471A.
158. Sharma P, Marrero JA, Fontana RJ, Greenson JK, Conjeevaram H, Su GL, et al. Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence. Liver Transpl 2007;13:1100-1108.
159. Casanovas-Taltavull T, Baliellas C, Benasco C, Serrano TT, Casanova A, Perez JL, et al. Efficacy of interferon for chronic hepatitis C virus-related hepatitis in kidney transplant candidates on hemodialysis: results after transplantation. Am J Gastroenterol 2001;96:1170-1177.
160. Luciani G, Bossola M, Muscaritoli M, Panocchia N, Ferrante A, Nanni G, et al. Sustained response with negative serum HCV-mRNA and disappearance of antibodies after interferon-alpha therapy in a kidney transplant recipient with chronic active viral hepatitis C. J Nephrol 2003;16:417-420.
161. Mahmoud IM, Sobh MA, El Habashi AF, Sally ST, El Baz M, El Sawy E, et al. Interferon therapy in hemodialysis patients with chronic hepatitis C: Study of tolerance, efficacy and post-transplantation course. Nephron Clin Pract 2005;100:c133-c139.
162. Bjoro K, Skaug K, Haaland T, Froland SS. Long-term outcome of chronic hepatitis C virus infection in primary hypogammaglobulinaemia. Q J Med 1999;92:433-441.
163. Shindo M, Arai K, Sokawa Y, Okuno T. Hepatic hepatitis C virus RNA as a predictor of a long-term response to interferon-alpha therapy. Ann Intern Med 1995;122:586-591.