IL28B polymorphism and genetic biomarkers of viral clearance in hepatitis C virus infection

Biomarkers in Medicine

Volumn 5, Issue 4, 2011, Pages 461-478

  Holmes, Jacinta A ^a   Sievert, William ^b   Thompson, Alexander J ^a  

^a ST VINCENT S HOSPITAL   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

genetic biomarkers; genome wide association study; hepatitis C virus; IFN l; IL28B; pegylated interferon; pharmacogenomics; ribavirin; single nucleotide polymorphism; spontaneous clearance; sustained virological response

Indexed keywords

ALPHA INTERFERON; INTERLEUKIN 28B; PEGINTERFERON; PLACEBO; RIBAVIRIN;

AFRICAN AMERICAN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL ACTIVITY; ETHNIC DIFFERENCE; EUROPEAN AMERICAN; GENE; GENE EXPRESSION; GENE FREQUENCY; GENE IDENTIFICATION; GENE LOCATION; GENETIC ASSOCIATION; GENETIC MARKER; GENETIC VARIABILITY; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HISPANIC; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IL28B GENE; INFLAMMATION; JAPANESE; KIRDL3 GENE; MARKER GENE; MIXED INFECTION; PHARMACOGENETICS; PHENOTYPE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT OUTCOME; VIRAL CLEARANCE; VIRUS ATTACHMENT;

ANTIVIRAL AGENTS; BIOLOGICAL MARKERS; CHROMOSOMES, HUMAN, PAIR 19; GENOME-WIDE ASSOCIATION STUDY; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; INTERLEUKINS; LIVER TRANSPLANTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; RNA, VIRAL;

HEPATITIS C VIRUS;

EID: 80052042080     PISSN: 17520363     EISSN: 17520371     Source Type: Journal    
DOI: 10.2217/bmm.11.47     Document Type: Review

References (111)

1. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect. Dis. 5(9), 558-567 (2005). (Pubitemid 41196755)
2. Manns MP, McHutchison JG, Gordon SC et al. Peginterferon a-2b plus ribavirin compared with IFN-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358(9286), 958-965 (2001). (Pubitemid 32913521)
3. Fried M W, Shiffman ML, Reddy KR et al. Peginterferon a-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347(13), 975-982 (2002).
4. Hadziyannis SJ, Sette H Jr, Morgan TR et al. Peginterferon-a2a and ribavirin combination therapy in chronic hepatitis C: a randomised study of treatment duration and ribavirin dose. Ann. Intern. Med. 140(4), 346-355 (2004).
5. Jacobson IM, Brown RS Jr, Freilich B et al. Peginterferon a-2b and weight-based or fat dosed ribavirin in chronic hepatitis C patients: a randomized trial. Hepatol. 46(4), 971-981 (2007). (Pubitemid 350144761)
6. McHutchison JG, Lawitz EJ, Shiffman ML et al. Peginterferon a-2b or a-2a with ribavirin for treatment of hepatitis C infection. N. Engl. J. Med. 361(6), 580-593 (2009).
7. Muir AJ, Bornstein JD, Killenberg PG. Peginterferon a-2b and ribavirin for the treatment of chronic hepatitis C in black and non-Hispanic whites. N. Engl. J. Med. 350(22), 2265-2271 (2004). (Pubitemid 38669209)
8. Conjeevaram HS, Fried MW, Jeffers LJ et al. Peginterferon and ribavirin treatment in African-American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology 131(2), 470-477 (2006). (Pubitemid 44142464)
9. Jeffers LJ, Cassidy W, Howell CD, Hu S, Reddy KR. Peginterferon a-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology 39(6), 1702-1708 (2004). (Pubitemid 38702672)
10. Shiffman ML, Mihas AA, Millwala F et al. Treatment of chronic hepatitis C virus in African-Americans with genotypes 2 and 3. Am. J. Gastroenterol. 102(4), 761-766 (2007). (Pubitemid 46496627)
11. The international HapMap Consortium. A haplotype map of the human genome. Nature 437(7063), 1299-1320 (2005).
12. Lander ES, Linton LM, Birren B et al. Initial sequencing and ana lysis of the human genome. Nature 409(6822), 860-921 (2001). (Pubitemid 32165345)
13. Ge D, Fellay J, Thompson AJ et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461(7262), 399-401 (2009).
14. Suppiah V, Moldovan M, Ahlenstiel G et al. IL28B is associated with response to chronic hepatitis C interferon-a and ribavirin therapy. Nat. Genet. 41(10), 1100-1104 (2009).
15. Tanaka Y, Nishida N, Sugiyama M et al. Genome-wide association of IL28B with response to pegylated interferon-a and ribavirin therapy for chronic hepatitis C. Nat. Genet. 41(10), 1105-1109 (2009).
16. Rauch A, Kutalik Z, Descombes P et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 138(4), 1338-1345 (2010).
17. Pearson TA, Manolio TA. How to interpret a genome-wide association study. JAMA 299, 11:1335-1344(2008). (Pubitemid 351439079)
18. Kotenko SV, Gallagher G, Baurin VV et al. IFN-ls mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4(1), 66-77 (2003).
19. Sheppard P, Kindsvogel W, Xu W et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat. Immunol. 4(1), 63-68 (2003). (Pubitemid 36104710)
20. Gad HH, Dellgren C, Hamming OJ, Vends S, Paludan SR, Hartmann R. Interferon-l is functionally an interferon but structurally related to the interleukin-10 family J. Biolog. Chem. 284(31), 20869-20875 (2009).
21. Li M, Liu X, Zhou Y, Su SB. Interferon-ls: the modulators of antivirus, antitumor, and immune responses. J. Leuk. Biol. 86(1), 23-32 (2009).
22. Fox BA, Sheppard PO, O'Hara PJ. The role of genomic data in the discovery, annotation and evolutionary interpretation of the interferon-l family. PLoS One 4, e4933 (2009).
23. Ank N, West H, Paludan SR. IFN-l. Novel antiviral cytokines. J. Inteferon Cytokine Res. 26, 373-379 (2006).
24. Ank N, Iversen MB, Bartholdy C et al. An important role for type III interferon (IFNl/IL28) in TLR-induced antiviral activity. J. Immunol. 180, 2474-2485 (2008).
25. Robek MD, Boyd BS, Chisari FV. l-interferon inhibits hepatitis B and C virus replication. J. Virol. 79(6), 3851-3854 (2005). (Pubitemid 40327973)
26. Marcello T, Grakoui A, Barba-Spaeth G et al. Interferons a and l inhibit HCV replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131(6), 1887-1898 (2006). (Pubitemid 44958521)
27. Yan KK, Guirgis M, Dinh T et al. Treatment responses in Asians and Caucasians with chronic hepatitis C infection. World J. Gastroenterol. 14, 3416-3420 (2008).
28. Liu CH, Liu CJ, Lin CL et al. Pegylated interferon-a-2a plus ribavirin for treatment-naïve Asian patients with hepatitis C virus genotype 1 infection: a multicenter, randomized controlled trial. Clin. Infect. Dis. 47, 1260-1269 (2008).
29. Thompson AJ, Muir AJ, Sulkowski MS et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pre-treatment predictor of sustained virological response in genotype 1 hepatitis C virus. Gastroenterology 139(1), 120-129 (2010).
30. Bochud PY, Bibert S, Negro F et al. IL28B polymorphisms predict reduction of HCV RNA from the frst day of therapy in chronic hepatitis C. J. Hepatol. DOI: 10.1016/j. jhep.2011.01.050 (2011) (Epub ahead of print).
31. McCarthy JJ, Li JH, Thompson A et al. Replicated association between an IL28 gene variant and a sustained response to pegylated interferon and ribavirin. Gastroenterology 138(7), 2307-2314 (2010).
32. Hayes CN, Kobayashi M, Akuta N et al. HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy. Gut. 60(2), 261-267 (2011).
33. Montes-Cano AM, García-Lozano JR, Abad-Molina C et al. Interleukin-28B genetic variants and hepatitis virus infection by different viral genotypes. Hepatology 52(1), 33-37 (2010).
34. Stättermayer AF, Stauber R, Hofer H et al. Impact of IL28B genotype on the early and sustained virological response in treatment-naïve patients with chronic hepatitis C. Clin. Gastroenterol. Hepatol. 9(4), 344-350.e2 (2010).
35. Mangia A, Santoro R, Minerva N et al. Peginterferon a-2b and ribavirin for 12 vs 24 weeks in HCV genotype 2 or 3. N. Engl. J. Med. 352(25), 2609-2617 (2005). (Pubitemid 41007847)
36. Mangia A, Thompson AJ, Santoro R et al. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virological response. Gastroenterology 139(3), 821-827 (2010).
37. Sarrazin C, Susser S, Doehring A et al. Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J. Hepatol. 54(3), 415-421 (2010).
38. Kawaoka T, Hayes CN, Ohishi W et al. Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b. J. Hepatol. 54(3), 408-414 (2010).
39. Scherzer TM, Hofer H, Stäettermayer AF et al. Early virological response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon a-2a and ribavirin. J. Hepatol. 54(5), 866-871 (2011).
40. Yu ML, Huang CF, Huang JF et al. Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus in genotype 2 infection in Asian patients. Hepatol. 53(1), 7-13 (2011).
41. Moghaddam A, Melum E, Reinton N et al. IL28B genetic variation and treatment response in patients with HCV genotype 3 infection. Hepatol. 53(3), 746-754 (2011).
42. Rallón NI, Naggie S, Benito JM et al. Association of a single nucleotide polymorphisms near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 24(8), F23-F29 (2010).
43. Grebely J, Petoumenos K, Hellard M et al. Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatol. 52(4), 1216-1224 (2010).
44. Nattermann J, Leifeld L, Spengler U. Host genetic factors and treatment of hepatitis C. Curr. Mol. Pharmacol. 1(2), 171-180 (2008).
45. Jaeckel E, Cornberg M, Wedemeyer H et al. Treatment of acute hepatitis C with interferon a-2b. NEJM 345 (20), 1452-1457 (2001).
46. Grebely J, Matthews GV, Dore GJ. Treatment of acute HCV infection. Nat. Rev. Gastroenterol. Hepatol. DOI: 10.1038/nrgastro.2011.32 (2011) (Epub ahead of print).
47. Aparicio E, Parera M, Franco S et al. IL28B SNP rs8099917 is strongly associated with pegylated interferon-a and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients. PLoS One 5(10), e13771 (2010).
48. Pineda JA, Caruz A, Rivero A et al. Prediction of response to pegylated interferon plus ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus. Clin. Infect. Dis. 51(7), 788-795 (2010).
49. Labarga P, Barreiro P, Mira JA et al. Impact of IL28B polymorphisms on response to peginterferon and ribavirin in HIV-hepatitis C virus-coinfected patients with prior nonresponse or relapse. AIDS 25(8), 1131-1133 (2011).
50. Brown RS. Hepatitis C and liver transplantation. Nature 436(7053), 973-978 (2005).
51. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 122(4), 889-896 (2002). (Pubitemid 34267271)
52. Moonka DK, Kim D, Kapke A, Brown KA, Yoshida A. The infuence of induction therapy on graft and patient survival in liver transplantation. Am. J. Transplant. 10(3), 590-601 (2010).
53. Fukuhara T, Taketomi A, Motomura T et al. Variants in IL28B in liver recipients and donors correlate with response to peginterferon and ribavirin therapy for recurrent hepatitis C. Gastroenterology 139(5), 1577-1585 (2010).
54. Charlton MR, Thompson A, Veldt BJ et al. Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection. Hepatology 53(1), 317-324 (2011).
55. Lange CM, Moradpour D, Doehring A et al. Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C liver graft reinfection. J. Hepatol. DOI: 10.1016/j. jhep.2010.10.037 (2010) (Epub ahead of press).
56. McHutchison JG, Everson GT, Gordon SC et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N. Engl. J. Med. 360(18), 1827-1838 (2009).
57. Hézode C, Forestier N, Duskeiko G et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N. Engl. J. Med. 360(18), 1839-1850 (2009).
58. McHutchison JG, Manns MP, Muir AJ et al. Telaprevir for previously treated chronic HCV infection. N. Engl. J. Med. 362(14), 1292-1303 (2010).
59. Jacobson IM, McHutchison JG, Dusheiko GM et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment-naive patients: fnal results of Phase 3 ADVANCE study. AASLD, Boston, MA, USA, 2010 (Abstract 211).
60. Kwo PY, Lawitz E, McCone J et al. Effcacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon a-2b and ribavirin in treatment-naïve patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label randomised multicentre Phase 2 trial. Lancet 376(9742), 705-716 (2010).
61. Poordad F, McCone J Jr, Bacon BR et al. Boceprevir for untreated chronic HCV genotype 1 infection. NEJM 364(13), 1195-1206 (2011).
62. Bacon BR, Gordon SC, Lawitz E et al. Boceprevir for previously treated chronic HCV genotype 1 infection. NEJM 364(13), 1207-1217 (2011).
63. Rong L, Dahari H, Ribeiro RM, Perelson AS. Rapid emergence of protease inhibitor resistance in hepatitis C. Sci. Transl. Med. 2(30), 30ra32 (2010).
64. Kieffer TL, Kwong AD, Picchio GR. Viral resistance to specifcally targeted antiviral therapies for hepatitis C (STAT-Cs). J. Antimicrob. Chemother. 65(2), 202-212 (2010).
65. Akuta N, Suzuki F, Hirakawa M et al. Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology 52(2), 421-429 (2010).
66. Jacobson IM, Catlett I, Marcellin P et al. Telaprevir substantially improved SVR rates across all IL28B genotypes in the ADVANCE trial. EASL, Berlin, Germany, 30 March-3 April 2011 (Abstract 1369).
67. Poordad F, Bronowicki JP, Gordon SC et al. IL28B polymorphism predicts virologic response in patients with hepatitis C genotype 1 treated with boceprevir (BOC) combination therapy. EASL, Berlin, Germany, 30 March-3 April 2011 (Abstract 12).
68. Thomas DL, Thio CL, Martin MP et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C. Nature. 461(7265), 798-801 (2009).
69. Tillmann HL, Thompson AJ, Patel K et al. A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology 139(5), 1586-1592 (2010).
70. Wiese M, Berr F, Lafrenz M, Porst H, Oesen U. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-centre outbreak in Germany: a 20-year multicentre study. Hepatol. 32(1), 91-96 (2000). (Pubitemid 30432371)
71. Wiese M, Grüngreiff K, Güthoff W, Lafrenz M, Oesen U, Porst H. Outcome in a hepatitis C (genotype 1b) single source outbreak in Germany-a 25-year multicentre study. J. Hepatol. 43(4), 590-598 (2005). (Pubitemid 41253225)
72. Muir AJ, Shiffman ML, Zaman A et al. Phase 1b study of pegylated interferon l-1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 52(3), 822-832 (2010).
73. McHutchison JG. The role of genetic markers in hepatitis C virus therapy: a major step for individualized care. Liver Int. 31(S1), 29-35 (2011).
74. Afdhal NH, McHutchison JG, Zeuzem S et al Hepatitis C pharmacogeneitcs: state of the art in 2010. Hepatology 53(1), 336-345 (2011).
75. Tavis JE, Donlin MJ, Aurora R, Fan X, Di Bisceglie AM. Prospects for personalising antiviral therapy for hepatitis C virus with pharmacogenetics. Genome Med. 3(2), 8 (2011).
76. Honda M, Sakai A, Yamashita T et al. Hepatic ISG expression is associated with Genetic variation in IL28B and the outcome of IFN therapy for CHC. Gastroenterology 139(2), 499-509 (2010).
77. Urban TJ, Thompson AJ, Bradrick SS et al. IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52(6), 1888-1896 (2010).
78. Dill MT, Duong FH, Vogt JE et al. Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology 140(3), 1021-1031 (2011).
79. Sarasin-Filipowicz M, Oakeley EJ, Duong FHT et al. Interferon signaling and treatment outcome in chronic hepatitis C. PNAS 105(19), 7034-7039 (2008). (Pubitemid 351754525)
80. Asselah T, Bieche I, Narguet S et al. Liver gene expression signature to predict response to pegylated interferon plus ribavirin combination therapy in patients with chronic hepatitis C. Gut 57(4), 516-524 (2008).
81. Chen L, Borozan I, Feld J et al. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology 128(5), 1437-1444 (2005). (Pubitemid 40712193)
82. Chen L, Borozan I, Sun J et al. Cell-type specifc gene expression signature in liver underlies response to interferon therapy in chronic hepatitis C infection. Gastroenterology 138(3), 1123-1133 (2010).
83. Shebl FM, Maeder D, Shao U, Prokunina-Olsson L, Schadt EE, O'Brien TT. In the absence of HCV infection, interferon stimulated gene expression in liver is not associated with IL28B genotype. Gastroenterology 139(4), 1422-1424 (2010).
84. Thompson AJ, Muir AJ, Sulkowski MS et al. Hepatitis C trials that combine investigational agents with pegylated interferon should be stratifed by interleukin-28B genotype. Hepatology 52(6), 2243-2244 (2010).
85. Maggi G, Bottelli R, Gola D et al. Serum cholesterol and chronic hepatitis C. Ital. J. Gastroenterol. 28(8), 436-440 (1996). (Pubitemid 27055699)
86. Jármay K, Karácsony G, Nagy A, Schaff Z. Change sin lipid metabolism in chronic hepatitis C. World J. Gastroenterol. 11(41), 6422-6428 (2005). (Pubitemid 43136876)
87. Siagris D, Christofdou M, Theocharis GJ et al. Serum lipid pattern in chronic hepatitis C: histological and virological correlations. J. Viral Hepat. 13(1), 56-61 (2006).
88. Polgreen PM, Fultz SL, Justice AC et al. Association of hypercholesterolaemia with hepatitis C virus infection in HIV-infected people. HIV Med. 5(3), 144-150 (2004). (Pubitemid 38765280)
89. Bedino R, Ghurani R, Nsuami M et al. Lipid abnormalities in HIV/hepatitis C virus-coinfected patients. HIV Med. 7(8), 530-536 (2006). (Pubitemid 44742353)
90. Toyoda H, Kumada T. Cholesterol and lipoprotein levels as predictors of response to interferon for hepatitis C. Ann. Intern. Med. 133(11), 921 (2000).
91. Minuk GY, Weinstein S, Kaita KD. Serum cholesterol and low-density lipoprotein cholesterol levels as predictors of response to interferon therapy for chronic hepatitis C. Ann. Intern. Med. 132(9), 761-762 (2000). (Pubitemid 30244182)
92. Gopal K, Johnson TC, Gopal S et al. Correlation between b-lipoprotein levels and outcome of hepatitis C treatment. Hepatology 44(2), 335-340 (2006). (Pubitemid 44214872)
93. Economou M, Milionis H, Filis S et al. Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C. J. Gastroenterol. Hepatol. 23(4), 586-591 (2007).
94. Sheridan DA, Price DA, Schmid ML et al. Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-a and ribavirin. Aliment. Pharmacol. Ther. 29(12), 1282-1290 (2009).
95. Poynard T, Ratziu V, McHutchison J et al. Effect of treatment with peginterferon or interferon A-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 38, 75-85 (2003). (Pubitemid 36775798)
96. Li JH, Lao XQ, Tillmann HL et al. Interferon-l genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection. Hepatology 51(56), 1904-1911 (2010).
97. Thompson AJ, Clark PJ, Zhu M et al. Genome wide-association study identifes IL28B polymorphism to be associated with baseline ALT and hepatic necro-infammatory activity n chronic hepatitis C patients enrolled in the IDEAL study. AASLD, Boston, MA, USA, 2010 (Abstract 1893).
98. Bedossa P, Pynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 24(2), 289-293 (1996). (Pubitemid 26260021)
99. Corey KE, Mendez-Navarro J, Gorospe EC, Zheng H, Chung RT. Early treatment improves outcomes in acute hepatitis C virus infection: a meta-ana lysis. J. Viral Hepat. 17(3), 201-207 (2010).
100. Khakoo SI, Thio CL, Martin MP et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305(5685), 872-874 (2004). (Pubitemid 39038423)
101. Romero V, Zúñiga J, Azocar J et al. Genetic interaction of KIR and G1M immunoglobulin allotypes differ in obese from non-obese individuals with type 2 diabetes. Mol. Immunol. 45(14), 3857-3862 (2008).
102. Knapp S, Warshow U, Hegazy D et al. Consistent benefcial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to HCV. Hepatology 51, 1168-1175 (2010).
103. Knapp S, Warshow U, Ho KM et al. A polymorphism in IL28B distinguishes exposed, uninfected individuals from spontaneous resolvers of HCV infection. Gastroenterol. DOI: 10.1053/j.gastro.2011.04.005 (2011) (Epub ahead of print).
104. Dring MM, Morrison MH, McSharry BP et al. Innate immune genes synergize to predict increased risk of chronic disease in HCV infection. PNAS 108(14), 5736-5741 (2011).
105. Hayashi K, Katano Y, Ishigami M et al. Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated interferon-a 2b and ribavirin combination therapy. J. Viral Hepat. 18(4), 280-286 (2011).
106. Akuta N, Suzuki F, Sezaki H et al. Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load. J. Med. Virology 78, 83-90 (2006). (Pubitemid 41783847)
107. Toyoda H, Kumada T, Kirivama S et al. High ability to predict the treatment outcome of peginterferon and ribavirin combination therapy based on the reduction in HCV RNA levels at 4 weeks after starting therapy and amino acid substitutions in the hepatitis C virus in patients infected with HCV genotype 1b. J. Gastroenterol. 46(4), 501-509 (2011).
108. Okanoue T, Itoh Y, Hashimoto H et al. Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-centre study. J. Gastroenterol. 44, 952-963 (2009).
109. Pascu M, Martus P, Höhne M et al. Sustained virological response in hepatitis C virus type 1b infected patients is predicted by the number of mutations within the NS5A-ISDR: a meta-ana lysis focused on geographical differences. Gut 53, 1345-1351 (2004). (Pubitemid 39120125)
110. Di Lulio J, Ciuff A, Fitzmaurice K et al. Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance. Hepatology 53(5), 1446-1454 (2011).
111. Morrow MP, Yan J, Pankhong P et al. IL-28B/IFN-l 3 drives granzyme B loading and signifcantly increases CTL killing activity in macaques. Mol. Ther. 18(9), 1714-1723 (2010).