• 1
    Seeff LB. Natural history of chronic hepatitis C. HEPATOLOGY 2002; 36 ( Suppl 1): S35-S46.
  • 2
    European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55: 245-264.
  • 3
    Alberti A. What are the comorbidities influencing the management of patients and the response to therapy in chronic hepatitis C? Liver Int 2009; 29 ( Suppl 1): 15-18.
  • 4
    Zeuzem S, Poordad F. Pegylated-interferon plus ribavirin therapy in the treatment of CHC: individualization of treatment duration according to on-treatment virologic response. Curr Med Res Opin 2010; 26: 1733-1743
  • 5
    Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009; 461: 798-801
  • 6
    Rauch A, Kutalik Z, Descombes P, Cai T, Di Iulio J, Mueller T, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010; 138: 1338-1345, 1345 e1331-1337.
  • 7
    Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399-401
  • 8
    Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009; 41: 1100-1104
  • 9
    Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009; 41: 1105-1109
  • 10
    Robek MD, Boyd BS, Chisari FV. Lambda interferon inhibits hepatitis B and C virus replication. J Virol 2005; 79: 3851-3854.
  • 11
    Marcello T, Grakoui A, Barba-Spaeth G, Machlin ES, Kotenko SV, MacDonald MR, et al. Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 2006; 131: 1887-1898.
  • 12
    Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A, Flamm S, et al. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. HEPATOLOGY 2010; 52: 822-832.
  • 13
    Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003; 4: 69-77.
  • 14
    Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 2006; 80: 4501-4509.
  • 15
    Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, et al. Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity. Blood 2009; 113: 5868-5877.
  • 16
    Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, et al. IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques. Mol Ther 2010; 18: 1714-1723.
  • 17
    Pilli M, Zerbini A, Penna A, Orlandini A, Lukasiewicz E, Pawlotsky JM, et al. HCV-specific T-cell response in relation to viral kinetics and treatment outcome (DITTO-HCV project). Gastroenterology 2007; 133: 1132-1143.
  • 18
    Mihm U, Herrmann E, Sarrazin C, Zeuzem S. Review article: predicting response in hepatitis C virus therapy. Aliment Pharmacol Ther 2006; 23: 1043-1054.
  • 19
    Buster EH, Hansen BE, Lau GK, Piratvisuth T, Zeuzem S, Steyerberg EW, et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology 2009; 137: 2002-2009.
  • 20
    Prasad L, Masserey V, Zwahlen M, Rickenbach M, Helbling B, Negro F. Cohort profile: the Swiss Hepatitis C Cohort Study. Int J Epidemiol 2007; 36: 731-737.
  • 21
    Nalpas B, Lavialle-Meziani R, Plancoulaine S, Jouanguy E, Nalpas A, Munteanu M, et al. Interferon gamma receptor 2 gene variants are associated with liver fibrosis in patients with chronic hepatitis C infection. Gut 2010; 59: 1120-1126.
  • 22
    Bochud PY, Biber S, Negro F, Haagmans B, Soulier A, Ferrari C, et al. IL28B polymorphisms significantly correlate with IFN antiviral effectiveness already on first day of pegylated interferon-α/ribavirin therapy of chronic HCV infection. J Hepatol 2011 [Epub ahead of print].
  • 23
    Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 2006; 130: 1636-1642.
  • 24
    Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349: 825-832.
  • 25
    Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. HEPATOLOGY 2005; 41: 1313-1321.
  • 26
    Cai T, Dufour JF, Muellhaupt B, Gerlach T, Heim M, Moradpour D, et al. Viral genotype-specific effect of PNPLA3, PPARG, IL28B and MTTP on hepatitis C virus-associated steatosis. J Hepatol 2011; 55: 529-535.
  • 27
    Bochud PY, Cai T, Overbeck K, Bochud M, Dufour JF, Mullhaupt B, et al. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol 2009; 51: 655-666.
  • 28
    Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35: 421-430.
  • 29
    Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, et al. Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol 2010; 53: 439-443.
  • 30
    Thompson A, Clark PJ, Zhu M, Zhu Q, Ge D, Sulkowski MS, et al. Genome-wide association study identifies IL28B polymorphisms to be associated with baseline ALT and hepatic necroinflammatory activity in chronic hepatitis C patients enrolled in the IDEAL study. HEPATOLOGY 2010; 52 ( Suppl): 1221A.
  • 31
    Thompson A, Clark PJ, Fellay J, Muir AJ, Tillmann HL, Patel K, et al. IL28B genotype is not associated with advanced hepatic fibrosis in chronic hepatitis C patients enrolled in the IDEAL study. HEPATOLOGY 2010; 52( Suppl): 437A.
  • 32
    Marabita F, Aghemo A, De Nicola S, Rumi MG, Cheroni C, Scavelli R, et al. Genetic variation in IL28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection. HEPATOLOGY 2011 doi:10.1002/hep.24503 [Epub ahead of print].
  • 33
    Nelson DR, Marousis CG, Ohno T, Davis GL, Lau JY. Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C. HEPATOLOGY 1998; 28: 225-230.
  • 34
    Freeman AJ, Marinos G, Ffrench RA, Lloyd AR. Intrahepatic and peripheral blood virus-specific cytotoxic T lymphocyte activity is associated with a response to combination IFN-alpha and ribavirin treatment among patients with chronic hepatitis C virus infection. J Viral Hepat 2005; 12: 125-129.
  • 35
    Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. HEPATOLOGY 2003; 37: 600-609.
  • 36
    McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361: 580-593.
  • 37
    Fiore G, Angarano I, Caccetta L, Serrone M, Jirillo E, Schiraldi O, et al. In-situ immunophenotyping study of hepatic-infiltrating cytotoxic cells in chronic active hepatitis C. Eur J Gastroenterol Hepatol 1997; 9: 491-496.
  • 38
    Khakoo SI, Soni PN, Savage K, Brown D, Dhillon AP, Poulter LW, et al. Lymphocyte and macrophage phenotypes in chronic hepatitis C infection. Correlation with disease activity. Am J Pathol 1997; 150: 963-970.
  • 39
    Leroy V, Vigan I, Mosnier JF, Dufeu-Duchesne T, Pernollet M, Zarski JP, et al. Phenotypic and functional characterization of intrahepatic T lymphocytes during chronic hepatitis C. HEPATOLOGY 2003; 38: 829-841.
  • 40
    Wong DK, Dudley DD, Afdhal NH, Dienstag J, Rice CM, Wang L, et al. Liver-derived CTL in hepatitis C virus infection: breadth and specificity of responses in a cohort of persons with chronic infection. J Immunol 1998; 160: 1479-1488.
  • 41
    Bonorino P, Ramzan M, Camous X, Dufeu-Duchesne T, Thélu MA, Sturm N, et al. Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C. J Hepatol 2009; 51: 458-467.
  • 42
    Pernollet M, Jouvin-Marche E, Leroy V, Vigan I, Zarski JP, Marche PN. Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions. Clin Exp Immunol 2002; 130: 518-525.
  • 43
    Freeman AJ, Pan Y, Harvey CE, Post JJ, Law MG, White PA, et al. The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection. J Hepatol 2003; 38: 349-356.
  • 44
    Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Karow M, Flavell RA. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 2007; 27: 647-659.
  • 45
    Fabris C, Falleti E, Cussigh A, Bitetto D, Fontanini E, Bignulin S, et al. IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol 2011; 54: 716-722.
  • 46
    Asahina Y, Tanaka K, Suzuki Y, Tamaki N, Hoshioka T, Kato T, et al. Association between IL28B gene variation and development of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C. J Hepatol 2011; 54( Suppl): S37.
  • 47
    Lasfar A, Lewis-Antes A, Smirnov SV, Anantha S, Abushahba W, Tian B, et al. Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Res 2006; 66: 4468-4477.
  • 48
    Sato A, Ohtsuki M, Hata M, Kobayashi E, Murakami T. Antitumor activity of IFN-lambda in murine tumor models. J Immunol 2006; 176: 7686-7694.
  • 49
    Li Q, Kawamura K, Ma G, Iwata F, Numasaki M, Suzuki N, et al. Interferon-lambda induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents. Eur J Cancer 2010; 46: 180-190.
  • 50
    Abushahba W, Balan M, Castaneda I, Yuan Y, Reuhl K, Raveche E, et al. Antitumor activity of type I and type III interferons in BNL hepatoma model. Cancer Immunol Immunother 2010; 59: 1059-1071.