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Semin Liver Dis 2007; 27(1): 013-027
DOI: 10.1055/s-2006-960168
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Genetics, Genomics, and Proteomics: Implications for the Diagnosis and the Treatment of Chronic Hepatitis C

Tarik Asselah1 , Ivan Bièche2 , Valérie Paradis3 , Pierre Bedossa3 , Michel Vidaud2 , Patrick Marcellin1
  • 1Service d'Hépatologie and INSERM U773, CRB3, University of Paris VII, AP-HP Hôpital Beaujon, Clichy, France
  • 2INSERM U745, University of Paris V, France
  • 3Service d'Anatomie Pathologique, AP-HP Hôpital Beaujon, Clichy, France
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Publikationsverlauf

Publikationsdatum:
12. Februar 2007 (online)

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ABSTRACT

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The severity of disease varies widely from mild illness to cirrhosis and hepatocellular carcinoma. The progression of liver fibrosis in HCV patients determines the prognosis and, thus, the need for and urgency of therapy. In addition to viral and environmental behavioral factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes of patients chronically infected with HCV. The sequencing of the human genome together with the development of high-throughput technologies has provided opportunities to distinguish discrete subsets of HCV disease and predict the disease outcome or the response to therapy. This article reviews genetic, genomic, and proteomic aspects associated with the natural history of HCV infection (i.e., viral clearance, fibrosis progression) and the response to therapy.

KEYWORDS

Microarray - HLA loci - fibrosis progression - prediction - pegylated interferon

REFERENCES

  • 1 Choo Q L, Kuo G, Weiner A J et al.. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.  Science. 1989;  244 359-362
    CrossrefPubMedGoogle Scholar
  • 2 Lanford R E, Bigger C, Bassett S, Klimpel G. The chimpanzee model of hepatitis C virus infections.  ILAR J. 2001;  42 117-126
    CrossrefPubMedGoogle Scholar
  • 3 Lohmann V, Korner F, Koch J et al.. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line.  Science. 1999;  285 110-113
    CrossrefPubMedGoogle Scholar
  • 4 Blight K J, Kolykhalov A A, Rice C M. Efficient initiation of HCV RNA replication in cell culture.  Science. 2000;  290 1972-1974
    CrossrefPubMedGoogle Scholar
  • 5 Wakita T, Pietschmann T, Kato T et al.. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome.  Nat Med. 2005;  11 791-796
    CrossrefPubMedGoogle Scholar
  • 6 Zhong J, Gastaminza P, Cheng G et al.. Robust hepatitis C virus infection in vitro.  Proc Natl Acad Sci USA. 2005;  102 9294-9299
    CrossrefPubMedGoogle Scholar
  • 7 Lindenbach B D, Evans M J, Syder A J et al.. Complete replication of hepatitis C virus in cell culture.  Science. 2005;  309 623-626
    CrossrefPubMedGoogle Scholar
  • 8 Gale Jr M, Foy E M. Evasion of intracellular host defence by hepatitis C virus.  Nature. 2005;  436 939-945
    CrossrefPubMedGoogle Scholar
  • 9 Foy E, Li K, Wang C et al.. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease.  Science. 2003;  300 1145-1148
    CrossrefPubMedGoogle Scholar
  • 10 Tan S L, Nakao H, He Y et al.. NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling.  Proc Natl Acad Sci USA. 1999;  96 5533-5538
    CrossrefPubMedGoogle Scholar
  • 11 Ghosh A K, Majumder M, Steele R et al.. Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP.  J Biol Chem. 2000;  275 7184-7188
    CrossrefPubMedGoogle Scholar
  • 12 Gong G, Waris G, Tanveer R, Siddiqui A. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B.  Proc Natl Acad Sci USA. 2001;  98 9599-9604
    CrossrefPubMedGoogle Scholar
  • 13 Polyak S J, Khabar K S, Paschal D M et al.. Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response.  J Virol. 2001;  75 6095-6106
    CrossrefPubMedGoogle Scholar
  • 14 Girard S, Shalhoub P, Lescure P et al.. An altered cellular response to interferon and up-regulation of interleukin-8 induced by the hepatitis C viral protein NS5A uncovered by microarray analysis.  Virology. 2002;  295 272-283
    CrossrefPubMedGoogle Scholar
  • 15 Ghosh A K, Majumder M, Steele R et al.. Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1.  Virology. 2003;  306 51-59
    CrossrefPubMedGoogle Scholar
  • 16 Girard S, Vossman E, Misek D E et al.. Hepatitis C virus NS5A-regulated gene expression and signaling revealed via microarray and comparative promoter analyses.  Hepatology. 2004;  40 708-718
    CrossrefPubMedGoogle Scholar
  • 17 Geiss G K, Carter V S, He Y et al.. Gene expression profiling of the cellular transcriptional network regulated by alpha/beta interferon and its partial attenuation by the hepatitis C virus nonstructural 5A protein.  J Virol. 2003;  77 6367-6375
    CrossrefPubMedGoogle Scholar
  • 18 Zhu Q, Guo J T, Seeger C. Replication of hepatitis C virus subgenomes in nonhepatic epithelial and mouse hepatoma cells.  J Virol. 2003;  77 9204-9210
    CrossrefPubMedGoogle Scholar
  • 19 Hayashi J, Stoyanova R, Seeger C. The transcriptome of HCV replicon expressing cell lines in the presence of alpha interferon.  Virology. 2005;  335 264-275
    CrossrefPubMedGoogle Scholar
  • 20 Keskinen P, Nyqvist M, Sareneva T et al.. Impaired antiviral response in human hepatoma cells.  Virology. 1999;  263 364-375
    CrossrefPubMedGoogle Scholar
  • 21 Bigger C B, Brasky K M, Lanford R E. DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection.  J Virol. 2001;  75 7059-7066
    CrossrefPubMedGoogle Scholar
  • 22 Bigger C B, Guerra B, Brasky K M et al.. Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees.  J Virol. 2004;  78 13779-13792
    CrossrefPubMedGoogle Scholar
  • 23 DeRisi J, Penland L, Brown P O et al.. Use of a cDNA microarray to analyse gene expression patterns in human cancer.  Nat Genet. 1996;  14 457-460
    PubMedGoogle Scholar
  • 24 Asselah T, Bieche I, Laurendeau I et al.. Liver gene expression signature of mild fibrosis in patients with chronic hepatitis C.  Gastroenterology. 2005;  129 2064-2075
    CrossrefPubMedGoogle Scholar
  • 25 Bieche I, Asselah T, Laurendeau I et al.. Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection.  Virology. 2005;  332 130-144
    CrossrefPubMedGoogle Scholar
  • 26 Helbig K J, Lau D T, Semendric L et al.. Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector.  Hepatology. 2005;  42 702-710
    CrossrefPubMedGoogle Scholar
  • 27 Alter H J, Bradley D W. Non-A, non-B hepatitis unrelated to the hepatitis C virus (non-ABC).  Semin Liver Dis. 1995;  15 110-120
    PubMedGoogle Scholar
  • 28 Dore G J, Thomas D L. Management and treatment of injection drug users with hepatitis C virus (HCV) infection and HCV/human immunodeficiency virus coinfection.  Semin Liver Dis. 2005;  25 18-32
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 29 Heller T, Rehermann B. Acute hepatitis C: a multifaceted disease.  Semin Liver Dis. 2005;  25 7-17
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Jaeckel E, Cornberg M, Wedemeyer H et al.. Treatment of acute hepatitis C with interferon alfa-2b.  N Engl J Med. 2001;  345 1452-1457
    CrossrefPubMedGoogle Scholar
  • 31 EASL International Consensus Conference on Hepatitis C Consensus statement.  J Hepatol. 1999;  30 956-961
    CrossrefPubMedGoogle Scholar
  • 32 National Institutes of Health Consensus Development Conference Statement. Management of Hepatitis C: 2002.  Hepatology. 2002;  36(suppl 1) S3-S21
    CrossrefPubMedGoogle Scholar
  • 33 Spada E, Mele A, Berton A et al.. Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance.  Gut. 2004;  53 1673-1681
    CrossrefPubMedGoogle Scholar
  • 34 Yee L J. Host genetic determinants in hepatitis C virus infection.  Genes Immun. 2004;  5 237-245
    CrossrefPubMedGoogle Scholar
  • 35 Congia M, Clemente M G, Dessi C et al.. HLA class II genes in chronic hepatitis C virus-infection and associated immunological disorders.  Hepatology. 1996;  24 1338-1341
    CrossrefPubMedGoogle Scholar
  • 36 Tibbs C, Donaldson P, Underhill J et al.. Evidence that the HLA DQA1*03 allele confers protection from chronic HCV-infection in Northern European Caucasoids.  Hepatology. 1996;  24 1342-1345
    CrossrefPubMedGoogle Scholar
  • 37 Alric L, Fort M, Izopet J et al.. Genes of the major histocompatibility complex class II influence the outcome of hepatitis C virus infection.  Gastroenterology. 1997;  113 1675-1681
    CrossrefPubMedGoogle Scholar
  • 38 Hohler T, Gerken G, Notghi A et al.. MHC class II genes influence the susceptibility to chronic active hepatitis C.  J Hepatol. 1997;  27 259-264
    CrossrefPubMedGoogle Scholar
  • 39 Cramp M E, Carucci P, Underhill J et al.. Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia.  J Hepatol. 1998;  29 207-213
    CrossrefPubMedGoogle Scholar
  • 40 Zavaglia C, Martinetti M, Silini E et al.. Association between HLA class II alleles and protection from or susceptibility to chronic hepatitis C.  J Hepatol. 1998;  28 1-7
    PubMedGoogle Scholar
  • 41 Kuzushita N, Hayashi N, Moribe T et al.. Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus.  Hepatology. 1998;  27 240-244
    CrossrefPubMedGoogle Scholar
  • 42 Minton E J, Smillie D, Neal K R et al.. Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group.  J Infect Dis. 1998;  178 39-44
    CrossrefPubMedGoogle Scholar
  • 43 Asti M, Martinetti M, Zavaglia C et al.. Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease.  Hepatology. 1999;  29 1272-1279
    CrossrefPubMedGoogle Scholar
  • 44 Mangia A, Gentile R, Cascavilla I et al.. HLA class II favors clearance of HCV infection and progression of the chronic liver damage.  J Hepatol. 1999;  30 984-989
    CrossrefPubMedGoogle Scholar
  • 45 Thursz M, Yallop R, Goldin R et al.. Influence of MHC class II genotype on outcome of infection with hepatitis C virus.  Lancet. 1999;  354 2119-2124
    CrossrefPubMedGoogle Scholar
  • 46 Barrett S, Ryan E, Crowe J. Association of the HLA-DRB1*01 allele with spontaneous viral clearance in an Irish cohort infected with hepatitis C virus via contaminated anti-D immunoglobulin.  J Hepatol. 1999;  30 979-983
    CrossrefPubMedGoogle Scholar
  • 47 Fanning L J, Levis J, Kenny-Walsh E et al.. HLA class II genes determine the natural variance of hepatitis C viral load.  Hepatology. 2001;  33 224-230
    CrossrefPubMedGoogle Scholar
  • 48 McKiernan S M, Hagan R, Curry M et al.. The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C.  Gastroenterology. 2000;  118 1124-1130
    CrossrefPubMedGoogle Scholar
  • 49 Thio C L, Gao X, Goedert J J et al.. HLA-Cw*04 and hepatitis C virus persistence.  J Virol. 2002;  76 4792-4797
    CrossrefPubMedGoogle Scholar
  • 50 McKiernan S M, Hagan R, Curry M et al.. Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source.  Hepatology. 2004;  40 108-114
    CrossrefPubMedGoogle Scholar
  • 51 Cook D N, Beck M A, Coffman T M et al.. Requirement of MIP-1 alpha for an inflammatory response to viral infection.  Science. 1995;  269 1583-1585
    PubMedGoogle Scholar
  • 52 Liu R, Paxton W A, Choe S et al.. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.  Cell. 1996;  86 367-377
    CrossrefPubMedGoogle Scholar
  • 53 Samson M, Libert F, Doranz B J et al.. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.  Nature. 1996;  382 722-725
    CrossrefPubMedGoogle Scholar
  • 54 Dean M, Carrington M, Winkler C et al.. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene.  Science. 1996;  273 1856-1862
    CrossrefPubMedGoogle Scholar
  • 55 Huang Y, Paxton W A, Wolinsky S M et al.. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression.  Nat Med. 1996;  2 1240-1243
    PubMedGoogle Scholar
  • 56 Michael N L, Chang G, Louie L G et al.. The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression.  Nat Med. 1997;  3 338-340
    CrossrefPubMedGoogle Scholar
  • 57 Woitas R P, Ahlenstiel G, Iwan A et al.. Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C.  Gastroenterology. 2002;  122 1721-1728
    CrossrefPubMedGoogle Scholar
  • 58 Hellier S, Frodsham A J, Hennig B J et al.. Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection.  Hepatology. 2003;  38 1468-1476
    PubMedGoogle Scholar
  • 59 Mangia A, Santoro R, D'agruma L, Andriulli A. HCV chronic infection and CCR5-delta32/delta32.  Gastroenterology. 2003;  124 868-869
    CrossrefPubMedGoogle Scholar
  • 60 Zhang M, Goedert J J, O'Brien T R. High frequency of CCR5-delta32 homozygosity in HCV-infected, HIV-1-uninfected hemophiliacs results from resistance to HIV-1.  Gastroenterology. 2003;  124 867-868
    CrossrefPubMedGoogle Scholar
  • 61 Promrat K, McDermott D H, Gonzalez C M et al.. Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C.  Gastroenterology. 2003;  124 352-360
    CrossrefPubMedGoogle Scholar
  • 62 Goulding C, McManus R, Murphy A et al.. The CCR5-delta32 mutation: impact on disease outcome in individuals with hepatitis C infection from a single source.  Gut. 2005;  54 1157-1161
    CrossrefPubMedGoogle Scholar
  • 63 Wasmuth H E, Werth A, Mueller T et al.. Haplotype-tagging RANTES gene variants influence response to antiviral therapy in chronic hepatitis C.  Hepatology. 2004;  40 327-334
    CrossrefPubMedGoogle Scholar
  • 64 Vidigal P G, Germer J J, Zein N N. Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin.  J Hepatol. 2002;  36 271-277
    PubMedGoogle Scholar
  • 65 Bataller R, Brenner D A. Liver fibrosis.  J Clin Invest. 2005;  115 209-218
    CrossrefPubMedGoogle Scholar
  • 66 Friedman S L. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications.  Nat Clin Pract Gastroenterol Hepatol. 2004;  1 98-105
    CrossrefPubMedGoogle Scholar
  • 67 Marcellin P, Asselah T, Boyer N. Fibrosis and disease progression in hepatitis C.  Hepatology. 2002;  36 S47-S56
    CrossrefPubMedGoogle Scholar
  • 68 Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter?.  Gut. 2006;  55 123-130
    CrossrefPubMedGoogle Scholar
  • 69 Okuda M, Li K, Beard M R et al.. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein.  Gastroenterology. 2002;  122 366-375
    PubMedGoogle Scholar
  • 70 Novo E, Marra F, Zamara E et al.. Dose dependent and divergent effects of superoxide anion on cell death, proliferation, and migration of activated human hepatic stellate cells.  Gut. 2006;  55 90-97
    CrossrefPubMedGoogle Scholar
  • 71 Neuman M G, Benhamou J P, Bourliere M et al.. Serum tumour necrosis factor-alpha and transforming growth factor-beta levels in chronic hepatitis C patients are immunomodulated by therapy.  Cytokine. 2002;  17 108-117
    CrossrefPubMedGoogle Scholar
  • 72 Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C.  Lancet. 1997;  349 825-832
    CrossrefPubMedGoogle Scholar
  • 73 Seeff L B. Natural history of chronic hepatitis C.  Hepatology. 2002;  36(suppl 1) S35-S46
    CrossrefPubMedGoogle Scholar
  • 74 Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.  N Engl J Med. 1999;  340 1228-1233
    CrossrefPubMedGoogle Scholar
  • 75 Wiese M, Berr F, Lafrenz M, Porst H, Oesen U. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in Germany: a 20-year multicenter study.  Hepatology. 2000;  32 91-96
    CrossrefPubMedGoogle Scholar
  • 76 Codes L, Asselah T, Cazals-Hatem D et al.. Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of menopause and steatosis and the potential benefit of hormone replacement therapy.  Gut. 2006; September 27;  , (Epub ahead of print)
    PubMedGoogle Scholar
  • 77 Czaja A J, Carpenter H, Santrach P J, Moore S B. DR human leukocyte antigens and disease severity in chronic hepatitis C.  J Hepatol. 1996;  24 666-673
    CrossrefPubMedGoogle Scholar
  • 78 Haruna Y, Miyamoto T, Yasunami R et al.. Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C.  J Hepatol. 2000;  32 837-842
    CrossrefPubMedGoogle Scholar
  • 79 Brandhagen D J, Gross Jr J B, Poterucha J J et al.. Human leukocyte antigen DR markers as predictors of progression to liver transplantation in patients with chronic hepatitis C.  Am J Gastroenterol. 2000;  95 2056-2060
    CrossrefPubMedGoogle Scholar
  • 80 Tillmann H L, Chen D F, Trautwein C et al.. Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease.  Gut. 2001;  48 714-718
    CrossrefPubMedGoogle Scholar
  • 81 Renou C, Halfon P, Pol S et al.. Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.  Gut. 2002;  51 585-590
    CrossrefPubMedGoogle Scholar
  • 82 Pirisi M, Scott C A, Avellini C et al.. Iron deposition and progression of disease in chronic hepatitis C: role of interface hepatitis, portal inflammation, and HFE missense mutations.  Am J Clin Pathol. 2000;  113 546-554
    CrossrefPubMedGoogle Scholar
  • 83 Erhardt A, Maschner-Olberg A, Mellenthin C et al.. HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis.  J Hepatol. 2003;  38 335-342
    CrossrefPubMedGoogle Scholar
  • 84 Hézode C, Cazeneuve C, Cou O et al.. Liver iron accumulation in patients with chronic active hepatitis C: prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesions.  J Hepatol. 1999;  31 979-984
    CrossrefPubMedGoogle Scholar
  • 85 Knoll A, Kreuzpaintner B, Kreuzpaintner E et al.. Hemochromatosis mutation in hepatitis C: histopathology.  Gastroenterology. 1998;  115 1307-1309
    PubMedGoogle Scholar
  • 86 Smith B C, Gorve J, Guzail M A et al.. Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C.  Hepatology. 1998;  27 1695-1699
    CrossrefPubMedGoogle Scholar
  • 87 Thorburn D, Curry G, Spooner R et al.. The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C.  Gut. 2002;  50 248-252
    CrossrefPubMedGoogle Scholar
  • 88 Cui J, Eitzman D T, Westrick R J et al.. Spontaneous thrombosis in mice carrying the factor V Leiden mutation.  Blood. 2000;  96 4222-4226
    PubMedGoogle Scholar
  • 89 Papatheodoridis G V, Papakonstantinou E, Andrioti E et al.. Thrombotic risk factors and extent of liver fibrosis in chronic viral hepatitis.  Gut. 2003;  52 404-409
    CrossrefPubMedGoogle Scholar
  • 90 Wright M, Goldin R, Hellier S et al.. Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection.  Gut. 2003;  52 1206-1210
    CrossrefPubMedGoogle Scholar
  • 91 Marra F, DeFranco R, Grappone C et al.. Expression of the thrombin receptor in human liver: up-regulation during acute and chronic injury.  Hepatology. 1998;  27 462-471
    CrossrefPubMedGoogle Scholar
  • 92 Kuzushita N, Hayashi N, Kanto T et al.. Involvement of transporter associated with antigen processing 2 (TAP2) gene polymorphisms in hepatitis C virus infection.  Gastroenterology. 1999;  116 1149-1154
    CrossrefPubMedGoogle Scholar
  • 93 Powell E E, Edwards-Smith C J, Hay J L et al.. Host genetic factors influence disease progression in chronic hepatitis C.  Hepatology. 2000;  31 828-833
    CrossrefPubMedGoogle Scholar
  • 94 Sonzogni L, Silvestri L, De Silvestri A et al.. Polymorphisms of microsomal epoxide hydrolase gene and severity of HCV-related liver disease.  Hepatology. 2002;  36 195-201
    CrossrefPubMedGoogle Scholar
  • 95 Wozniak M A, Itzhaki R F, Faragher E B et al.. Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus.  Hepatology. 2002;  36 456-463
    CrossrefPubMedGoogle Scholar
  • 96 Strnad P, Lienau T C, Tao G Z et al.. Keratin variants associate with progression of fibrosis during chronic hepatitis C infection.  Hepatology. 2006;  43 1354-1363
    CrossrefPubMedGoogle Scholar
  • 97 Adinolfi L E, Ingrosso D, Cesaro G et al.. Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients.  Hepatology. 2005;  41 995-1003
    CrossrefPubMedGoogle Scholar
  • 98 Huang H, Shiffman M L, Cheung R C et al.. Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C.  Gastroenterology. 2006;  130 1679-1687
    CrossrefPubMedGoogle Scholar
  • 99 Romero-Gomez M, Montes-Cano M A, Otero-Fernandez M A et al.. SLC11A1 promoter gene polymorphisms and fibrosis progression in chronic hepatitis C.  Gut. 2004;  53 446-450
    CrossrefPubMedGoogle Scholar
  • 100 Hamada H, Yatsuhashi H, Yano K et al.. Interleukin-10 promoter polymorphisms and liver fibrosis progression in patients with chronic hepatitis C in Japan.  J Hepatol. 2003;  39 457-458
    CrossrefPubMedGoogle Scholar
  • 101 Muhlbauer M, Bosserhoff A K, Hartmann A et al.. A novel MCP-1 gene polymorphism is associated with hepatic MCP-1 expression and severity of HCV-related liver disease.  Gastroenterology. 2003;  125 1085-1093
    CrossrefPubMedGoogle Scholar
  • 102 Omary M B, Ku N O, Toivola D M. Keratins: guardians of the liver.  Hepatology. 2002;  35 251-257
    CrossrefPubMedGoogle Scholar
  • 103 Goh P Y, Tan Y J, Lim S P et al.. Cellular RNA helicase p68 relocalization and interaction with the hepatitis C virus (HCV) NS5B protein and the potential role of p68 in HCV RNA replication.  J Virol. 2004;  78 5288-5298
    CrossrefPubMedGoogle Scholar
  • 104 Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C.  Hepatology. 2003;  38 1449-1457
    CrossrefPubMedGoogle Scholar
  • 105 Honda M, Kaneko S, Kawai H et al.. Differential gene expression between chronic hepatitis B and C hepatic lesion.  Gastroenterology. 2001;  120 955-966
    CrossrefPubMedGoogle Scholar
  • 106 Shackel N A, McGuinness P H, Abbott C A et al.. Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression.  Am J Pathol. 2002;  160 641-654
    PubMedGoogle Scholar
  • 107 Smith M W, Yue Z N, Korth M J et al.. Hepatitis C virus and liver disease global transcriptional profiling and identification of potential markers.  Hepatology. 2003;  38 1458-1467
    PubMedGoogle Scholar
  • 108 Neuman M G, Benhamou J P, Malkiewicz I M et al.. Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis.  J Viral Hepat. 2002;  9 134-140
    CrossrefPubMedGoogle Scholar
  • 109 Pockros P J, Patel K, O'Brien C et al.. A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy.  Hepatology. 2003;  37 1368-1374
    CrossrefPubMedGoogle Scholar
  • 110 Marcellin P, Boyer N, Gervais A et al.. Long term histologic improvement and disappearance of intra hepatic HCV RNA after alpha interferon therapy in patients with chronic hepatitis C.  Ann Intern Med. 1997;  127 875-881
    PubMedGoogle Scholar
  • 111 Manns M P, McHutchison J G, Gordon S C et al.. Peginterferon alfa-2b plus ribavirin compared with IFN-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.  Lancet. 2001;  358 958-965
    CrossrefPubMedGoogle Scholar
  • 112 Fried M W, Shiffman M L, Reddy K R et al.. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.  N Engl J Med. 2002;  347 975-982
    CrossrefPubMedGoogle Scholar
  • 113 Hadziyannis S J, Sette Jr H, Morgan T R et al.. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.  Ann Intern Med. 2004;  140 346-355
    CrossrefPubMedGoogle Scholar
  • 114 Matsushita M, Hijikata M, Ohta Y, Mishiro S. Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients.  J Hepatol. 1998;  29 695-700
    CrossrefPubMedGoogle Scholar
  • 115 Edwards-Smith C J, Jonsson J R, Purdie D M et al.. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alpha.  Hepatology. 1999;  30 526-530
    CrossrefPubMedGoogle Scholar
  • 116 Yee L J, Tang J, Gibson A W et al.. Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection.  Hepatology. 2001;  33 708-712
    CrossrefPubMedGoogle Scholar
  • 117 Coelho-Borges S, Cheinquer H, Cheinquer N et al.. HFE gene mutations prevent sustained virological response to interferon plus ribavirin in chronic hepatitis C patients with serum markers of iron overload.  Am J Gastroenterol. 2002;  97 1570-1572
    CrossrefPubMedGoogle Scholar
  • 118 Hennig B J, Hellier S, Frodsham A J et al.. Association of low-density lipoprotein receptor polymorphisms and outcome of hepatitis C infection.  Genes Immun. 2002;  3 359-367
    CrossrefPubMedGoogle Scholar
  • 119 Rosen H R, McHutchison J G, Conrad A J et al.. Tumor necrosis factor genetic polymorphisms and response to antiviral therapy in patients with chronic hepatitis C.  Am J Gastroenterol. 2002;  97 714-720
    CrossrefPubMedGoogle Scholar
  • 120 Vidigal P G, Germer J J, Zein N N. Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin.  J Hepatol. 2002;  36 271-277
    PubMedGoogle Scholar
  • 121 Woitas R P, Sippel M, Althausen E M et al.. Differential expansion of T-cell receptor variable beta subsets after antigenic stimulation in patients with different outcomes of hepatitis C infection.  Immunology. 2002;  106 419-427
    CrossrefPubMedGoogle Scholar
  • 122 Chen L, Borozan I, Feld J et al.. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection.  Gastroenterology. 2005;  128 1437-1444
    CrossrefPubMedGoogle Scholar
  • 123 Hayashida K, Daiba A, Sakai A et al.. Pretreatment prediction of interferon-alfa efficacy in chronic hepatitis C patients.  Clin Gastroenterol Hepatol. 2005;  3 1253-1259
    CrossrefPubMedGoogle Scholar
  • 124 Ji X, Cheung R, Cooper S et al.. Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C.  Hepatology. 2003;  37 610-621
    CrossrefPubMedGoogle Scholar
  • 125 Butera D, Marukian S, Iwamaye A E et al.. Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C.  Blood. 2005;  106 1175-1182
    CrossrefPubMedGoogle Scholar
  • 126 Kingsmore S F. Multiplexed protein measurement: technologies and applications of protein and antibody arrays.  Nat Rev Drug Discov. 2006;  5 310-320
    CrossrefPubMedGoogle Scholar
  • 127 Jacobs J M, Diamond D L, Chan E Y et al.. Proteome analysis of liver cells expressing a full-length hepatitis C virus replicon and biopsy specimens of posttransplantation liver from HCV-infected patients.  J Virol. 2005;  79 7558-7569
    CrossrefPubMedGoogle Scholar
  • 128 Low T Y, Leow C K, Salto-Tellez M et al.. A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers.  Proteomics. 2004;  4 3960-3974
    CrossrefPubMedGoogle Scholar
  • 129 Kristensen D B, Kawada N, Imamura K et al.. Proteome analysis of rat hepatic stellate cells.  Hepatology. 2000;  32 268-277
    CrossrefPubMedGoogle Scholar
  • 130 Xu X Q, Leow C K, Lu X et al.. Molecular classification of liver cirrhosis in a rat model by proteomics and bioinformatics.  Proteomics. 2004;  4 3235-3245
    CrossrefPubMedGoogle Scholar
  • 131 Poon T C, Hui A Y, Chan H L et al.. Prediction of liver fibrosis and cirrhosis in chronic hepatitis B infection by serum proteomic fingerprinting: a pilot study.  Clin Chem. 2005;  51 328-335
    CrossrefPubMedGoogle Scholar
  • 132 Paradis V, Asselah T, Dargere D. Serum proteome to predict virologic response in patients with hepatitis C treated by pegylated interferon plus ribavirin.  Gastroenterology. 2006;  130 2189-2197
    CrossrefPubMedGoogle Scholar

Prof. Patrick Marcellin

Service d'Hépatologie, Hôpital Beaujon

100 Bd du Gl Leclerc, 92110 Clichy, France

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