Journal of Hepatology
Volume 50, Issue 4 , Pages 705-711 , April 2009

Hepatic SOCS3 expression is strongly associated with non-response to therapy and race in HCV and HCV/HIV infection

  • Kyung-Ah Kim

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
    • Department of Medicine, Ilsan Paik Hospital, Inje University, Goyang, Republic of Korea
  • ,
  • Wenyu Lin

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
  • ,
  • Andrew W. Tai

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
  • ,
  • Run-Xuan Shao

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
  • ,
  • Ethan Weinberg

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
  • ,
  • Carolina B. De Sa Borges

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
  • ,
  • Atul K. Bhan

      Affiliations

    • Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • ,
  • Hui Zheng

      Affiliations

    • Biostatistics Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • ,
  • Yoshitaka Kamegaya

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
  • ,
  • Raymond T. Chung

      Affiliations

    • Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 617 724 7562; fax: +1 617 643 0446.

Received 29 May 2008 ,Revised 11 November 2008 ,Accepted 9 December 2008.

References 

  1. Dienstag JL, McHutchison J. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology. 2006;130:231–264
  2. Di Bisceglie AM, Hooofnagle JH. Optimal therapy of hepatitis C. Hepatology. 2002;36:S121–S127
  3. 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
  4. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med. 2000;343:1666–1672
  5. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology. 2003;38:645–652
  6. Murashima S, Kumashiro R, Ide T, Miyajima I, Hino T, Koga Y, et al. Effect of interferon treatment on serum 2′,5′-oligoadenylate synthetase levels in hepatitis C-infected patients. J Med Virol. 2000;62:185–190
  7. Knapp S, Yee LJ, Frodsham AJ, Hennig BJ, Hellier S, Zhang L, et al. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR. Genes Immun. 2003;4:411–419
  8. MacQuillan GC, de Boer WB, Platten MA, McCaul KA, Reed WD, Jeffrey GP, et al. Intrahepatic MxA and PKR protein expression in chronic hepatitis C virus infection. J Med Virol. 2002;68:197–205
  9. 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
  10. 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
  11. Walsh MJ, Jonsson 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 signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1. Gut. 2006;55:529–535
  12. 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
  13. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451–459
  14. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699
  15. Song MM, Shuai K. The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem. 1998;273:35056–35062
  16. Persico M, Capasso M, Persico E, Svelto M, Russo R, Spano D, et al. Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: Insulin resistance and response to antiviral therapy. Hepatology. 2007;46:1009–1015
  17. Persico M, Capasso M, Russo R, Persico E, Croce L, Tiribelli C, et al. Elevated expression and polymorphisms of SOCS3 influence patient response to antiviral therapy in chronic hepatitis C. Gut. 2008;57:507–515
  18. Zimmerer JM, Lesinski GB, Kondadasula SV, Karpa VI, Lehman A, Raychaudhury A, et al. IFN-alpha-induced signal transduction, gene expression, and antitumor activity of immune effector cells are negatively regulated by suppressor of cytokine signaling proteins. J Immunol. 2007;178:4832–4845
  19. Chen L, Borozan I, Feld J, 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
  20. Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terracciano L, Filipowicz W, et al. Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci USA. 2008;105:7034–7039
  21. White PA, Pan Y, Freeman AJ, Marinos G, French RA, Lloyd AR, et al. Quantification of hepatitis C virus in human liver and serum samples by using LightCycler reverse transcriptase PCR. J Clin Microbiol. 2002;40:4346–4348

 Financial support: NIH AI069939, DK078772 (to R.T.C.) and Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship (to A.W.T.). 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(09)00012-9

doi: 10.1016/j.jhep.2008.12.021

Journal of Hepatology
Volume 50, Issue 4 , Pages 705-711 , April 2009