Journal of Hepatology
Volume 50, Issue 2 , Pages 412-420 , February 2009

Treatment failure in hepatitis C: Mechanisms of non-response

References 

  1. Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell. 1998;1:507–518
  2. Shin EC, Seifert U, Kato T, Rice CM, Feinstone SM, Kloetzel PM, et al. Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection. J Clin Invest. 2006;116:3006–3014
  3. Tough DF, Borrow P, Sprent J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science. 1996;272:1947–1950
  4. Luft T, Pang KC, Thomas E, Hertzog P, Hart DN, Trapani J, et al. Type I IFNs enhance the terminal differentiation of dendritic cells. J Immunol. 1998;161:1947–1953
  5. Santini SM, Lapenta C, Logozzi M, Parlato S, Spada M, Di Pucchio T, et al. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp Med. 2000;191:1777–1788
  6. Willberg CB, Ward SM, Clayton RF, Naoumov NV, McCormick C, Proto S, et al. Protection of hepatocytes from cytotoxic T cell mediated killing by interferon-alpha. PLoS ONE. 2007;2:e791
  7. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965
  8. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  9. Kau A, Vermehren J, Sarrazin C. Treatment predictors of a sustained virologic response in hepatitis B and C. J Hepatol. 2008;49:634–651
  10. Kamal SM, Fouly AE, Kamel RR, Hockenjos B, Al Tawil A, Khalifa KE, et al. Peginterferon alfa-2b therapy in acute hepatitis C: impact of onset of therapy on sustained virologic response. Gastroenterology. 2006;130:632–638
  11. Wiegand J, Buggisch P, Boecher W, Zeuzem S, Gelbmann CM, Berg T, et al. Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. Hepatology. 2006;43:250–256
  12. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005;437:1167–1172
  13. Li XD, Sun L, Seth RB, Pineda G, Chen ZJ. Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA. 2005;102:17717–17722
  14. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, et al. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA. 2005;102:2992–2997
  15. Bode JG, Ludwig S, Ehrhardt C, Albrecht U, Erhardt A, Schaper F, et al. IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. FASEB J. 2003;17:488–490
  16. Lin W, Choe WH, Hiasa Y, Kamegaya Y, Blackard JT, Schmidt EV, et al. Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. Gastroenterology. 2005;128:1034–1041
  17. Lin W, Kim SS, Yeung E, Kamegaya Y, Blackard JT, Kim KA, et al. Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain. J Virol. 2006;80:9226–9235
  18. Duong FH, Filipowicz M, Tripodi M, La Monica N, Heim MH. Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology. 2004;126:263–277
  19. Gale M, Korth MJ, Tang NM, Tan SL, Hopkins DA, Dever TE, et al. Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology. 1997;230:217–227
  20. Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science. 1999;285:107–110
  21. Han JQ, Barton DJ. Activation and evasion of the antiviral 2′-5′ oligoadenylate synthetase/ribonuclease L pathway by hepatitis C virus mRNA. RNA. 2002;8:512–525
  22. Kanto T, Hayashi N, Takehara T, Tatsumi T, Kuzushita N, Ito A, et al. Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. J Immunol. 1999;162:5584–5591
  23. Auffermann-Gretzinger S, Keeffe EB, Levy S. Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood. 2001;97:3171–3176
  24. Kittlesen DJ, Chianese-Bullock KA, Yao ZQ, Braciale TJ, Hahn YS. Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. J Clin Invest. 2000;106:1239–1249
  25. Francavilla V, Accapezzato D, De Salvo M, Rawson P, Cosimi O, Lipp M, et al. Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms. Eur J Immunol. 2004;34:427–437
  26. Gruener NH, Lechner F, Jung MC, Diepolder H, Gerlach T, Lauer G, et al. Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J Virol. 2001;75:5550–5558
  27. Timm J, Lauer GM, Kavanagh DG, Sheridan I, Kim AY, Lucas M, et al. CD8 epitope escape and reversion in acute HCV infection. J Exp Med. 2004;200:1593–1604
  28. Muir AJ, Bornstein JD, Killenberg PG, Atlantic Coast Hepatitis Treatment Group . Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004;350:2265–2271
  29. Jeffers LJ, Cassidy W, Howell CD, Hu S, Reddy KR. Peginterferon alfa-2a (40kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology. 2004;39:1702–1708
  30. Conjeevaram HS, Fried MW, Jeffers LJ, Terrault NA, Wiley-Lucas TE, Afdhal N, et al. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology. 2006;131:470–477
  31. Howell CD, Dowling TC, Paul M, Wahed AS, Terrault NA, Taylor M, et al. Peginterferon pharmacokinetics in African American and Caucasian American patients with hepatitis C virus genotype 1 infection. Clin Gastroenterol Hepatol. 2008;6:575–583
  32. Taylor MW, Tsukahara T, Brodsky L, Schaley J, Sanda C, Stephens MJ, et al. Changes in gene expression during pegylated interferon and ribavirin therapy of chronic hepatitis C virus distinguish responders from nonresponders to antiviral therapy. J Virol. 2007;81:3391–3401
  33. Rosen HR, Weston SJ, Im K, Yang H, Burton JR, Erlich H, et al. Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy. Hepatology. 2007;46:350–358
  34. Donlin MJ, Cannon NA, Yao E, Li J, Wahed A, Taylor MW, et al. Pretreatment sequence diversity differences in the full-length hepatitis C virus open reading frame correlate with early response to therapy. J Virol. 2007;81:8211–8224
  35. Chen L, Borozan I, Feld JJ, Sun J, Tannis LL, Coltescu C, et al. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology. 2005;128:1437–1444
  36. Feld JJ, Nanda S, Huang Y, Chen W, Cam M, Pusek SN, et al. Hepatic gene expression during treatment with peginterferon and ribavirin: identifying molecular pathways for treatment response. Hepatology. 2007;46:1548–1563
  37. Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terraciano L, Filipowicz M, et al. Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci USA. 2008;105:7034–7039
  38. Huang Y, Feld JJ, Sapp RK, Nanda S, Lin JH, Blatt LM, et al. Defective hepatic response to interferon and activation of suppressor of cytokine signaling 3 in chronic hepatitis C. Gastroenterology. 2007;132:733–744
  39. Su X, Lee LJ, Im K, Rhodes SL, Tang Y, Tong X, et al. Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C. J Hepatol. 2008;49:184–191
  40. Conjeevaram HS, Kleiner DE, Everhart JE, Hoofnagle JH, Zacks S, AFdhal NH, et al. Race, insulin resistance and hepatic steatosis in chronic hepatitis C. Hepatology. 2007;45:80–87
  41. Romero-Gómez M, Del Mar Viloria M, Andrade RJ, Salmerón J, Diago M, Fernández-Rodríguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636–641
  42. Walsh MJ, Johnsson JR, Richardson MM, Lipka GM, Purdie DM, Clouston AD, et al. Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1. Gut. 2006;55:529–535
  43. Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol. 2004;165:1499–1508
  44. Leroy V, Baud M, de Traversay C, Maynard-Muet M, Lebon P, Zarski JP. Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C. J Hepatol. 1998;28:375–381
  45. Hou C, Chuang WL, Yu ML, Dai CY, Chen SC, Lin ZY, et al. Incidence and associated factors of neutralizing anti-interferon antibodies among chronic hepatitis C patients treated with interferon in Taiwan. Scand J Gastroenterol. 2000;35:1288–1293
  46. Liang Y, Ishida H, Lenz O, Lin TI, Nyanguile O, Simmen K, et al. Antiviral suppression vs restoration of RIG-I signaling by hepatitis C protease and polymerase inhibitors. Gastroenterology. 2008;135:1710–1718
  47. Duong FH, Christen V, Filipowicz M, Heim MH. S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro. Hepatology. 2006;43:796–806
  48. Hofmann WP, Polta A, Herrmann E, Mihm U, Kronenberger B, Sonntag T, et al. Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy. Gastroenterology. 2007;132:921–930
  49. Lutchman G, Danehower S, Song BC, Liang TJ, Hoofnagle JH, Thomson M, et al. Mutation rate of the hepatitis C virus NS5B in patients undergoing treatment with ribavirin monotherapy. Gastroenterology. 2007;132:1757–1766
  50. Chevaliez S, Brillet R, Lázaro E, Hézode C, Pawlotsky JM. Analysis of ribavirin mutagenicity in human hepatitis C virus infection. J Virol. 2007;81:7732–7741
  51. Shiffman ML, Salvatore J, Hubbard S, Price A, Sterling RK, Stravitz RT, et al. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology. 2007;46:371–379
  52. Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell. 2005;19:111–122
  53. Flisiak R, Horban A, Gallay P, Bobardt M, Selvarajah S, Wiercinska-Drapalo A, et al. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology. 2008;47:817–826
  54. Wang C, Gale M, Keller BC, Huang H, Brown MS, Goldstein JL, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell. 2005;18:425–434
  55. Ye J, Wang C, Sumpter R, Brown MS, Goldstein JL, Gale M. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci USA. 2003;100:15865–15870

☆ NIH funded study: AI080122, AI069939, and DK078772. The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

PII: S0168-8278(08)00767-8

doi: 10.1016/j.jhep.2008.11.010

Journal of Hepatology
Volume 50, Issue 2 , Pages 412-420 , February 2009

Article Tools

* Image Usage & Resolution