Skip to main content

Advertisement

Log in

The Influence of Anti-TNF Therapy on the Course of Chronic Hepatitis C Virus Infection in Patients with Inflammatory Bowel Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

The immunosuppressive potential of anti-tumor necrosis factor (TNF) in exacerbating chronic hepatitis C virus (HCV) infection has been a major concern. We aim to critically analyze the impact of anti-TNF on the course of chronic HCV infection in patients with concurrent inflammatory bowel disease (IBD) and HCV infection.

Materials and Methods

Patients with diagnosis of IBD and HCV were identified retrospectively through the University of Pennsylvania Health System electronic database. Data assessed included demographics, duration of IBD and HCV infection, HCV RNA levels, HCV genotype, liver histology, hepatic biochemical tests (HBT) and IBD disease activity index.

Results

A total of 4,274 IBD and 3,523 HCV patients were identified from 10/1998 to 05/2010. Thirty-seven patients had concurrent HCV infection and IBD, of which 23 patients were eligible (61 % CD; 39 % UC). Five patients (22 %) received anti-TNF therapy (infliximab). Two patients received pegylated interferon and ribavirin (both were non-responders). Overall, three patients had clinical remission and one patient had clinical response to infliximab. When compared to baseline, one patient had HBT improvement, three patients remained stable and one patient had HBT elevation, which was likely due to progressive liver disease in view of HIV co-infection.

Conclusion

This represents the first critical analysis assessing the impact of anti-TNF therapy on the course of chronic HCV in IBD patients. Concurrent HCV infection in IBD patients is uncommon. Treatment of IBD with infliximab in HCV patients did not result in flares in hepatic biochemical tests while there was an improvement in the IBD disease activity score.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Peyrin-Biroulet L, Deltenre P, de Suray N, et al. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008;6:644–653.

    Article  PubMed  CAS  Google Scholar 

  2. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.

    Article  PubMed  CAS  Google Scholar 

  3. Velayos FS, Sandborn WJ. Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor-alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis. 2004;10:657–660.

    Article  PubMed  Google Scholar 

  4. Toruner M, Loftus EV Jr, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134:929–936.

    Article  PubMed  Google Scholar 

  5. Strader DB, Wright T, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:1147–1171.

    Article  PubMed  Google Scholar 

  6. Kallinowski B, Haseroth K, Marinos G, et al. Induction of tumour necrosis factor (TNF) receptor type p55 and p75 in patients with chronic hepatitis C virus (HCV) infection. Clin Exp Immunol. 1998;111:269–277.

    Article  PubMed  CAS  Google Scholar 

  7. Kishihara Y, Hayashi J, Yoshimura E, et al. IL-1 beta and TNF-alpha produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C. Dig Dis Sci. 1996;41:315–321.

    Article  PubMed  CAS  Google Scholar 

  8. Nelson DR, Lim HL, Marousis CG, et al. Activation of tumor necrosis factor-alpha system in chronic hepatitis C virus infection. Dig Dis Sci. 1997;42:2487–2494.

    Article  PubMed  CAS  Google Scholar 

  9. Fukuda R, Ishimura N, Ishihara S, et al. Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C. Liver. 1996;16:390–399.

    PubMed  CAS  Google Scholar 

  10. Larrea E, Garcia N, Qian C, et al. Tumor necrosis factor alpha gene expression and the response to interferon in chronic hepatitis C. Hepatology. 1996;23:210–217.

    PubMed  CAS  Google Scholar 

  11. Calabrese LH, Zein N, Vassilopoulos D. Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic viral infections: hepatitis C, hepatitis B, and HIV infection. Ann Rheum Dis. 2004;63:ii18–ii24.

    Article  PubMed  CAS  Google Scholar 

  12. Zein NN. Etanercept as an adjuvant to interferon and ribavirin in treatment-naive patients with chronic hepatitis C virus infection: a phase 2 randomized, double-blind, placebo-controlled study. J Hepatol. 2005;42:315–322.

    Article  PubMed  CAS  Google Scholar 

  13. Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1:514.

    Article  PubMed  CAS  Google Scholar 

  14. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–1629.

    Article  PubMed  CAS  Google Scholar 

  15. Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666.

    Article  PubMed  Google Scholar 

  16. Vermeire S, Schreiber S, Sandborn WJ, et al. Correlation between the Crohn’s disease activity and Harvey–Bradshaw indices in assessing Crohn’s disease severity. Clin Gastroenterol Hepatol. 2010;8:357–363.

    Article  PubMed  Google Scholar 

  17. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–1374.

    Article  PubMed  CAS  Google Scholar 

  18. Abdelmalek MF, Liu C, Valentine JF. Successful treatment of chronic hepatitis C with pegylated interferon, ribavirin, and infliximab in a patient with Crohn’s disease. Am J Gastroenterol. 2007;102:1333–1334.

    Article  PubMed  Google Scholar 

  19. Campbell S, Ghosh S. Infliximab therapy for Crohn’s disease in the presence of chronic hepatitis C infection. Eur J Gastroenterol Hepatol. 2001;13:191–192.

    Article  PubMed  CAS  Google Scholar 

  20. Holtmann MH, Galle PR, Neurath MF. Treatment of patients with Crohn’s disease and concomitant chronic hepatitis C with a chimeric monoclonal antibody to TNF. Am J Gastroenterol. 2003;98:504–505.

    Article  PubMed  Google Scholar 

  21. Biancone L, Del Vecchio Blanco G, Pallone F, et al. Immunomodulatory drugs in Crohn’s disease patients with hepatitis B or C virus infection. Gastroenterology. 2002;122:593–594.

    Article  PubMed  Google Scholar 

  22. Katsanos KH, Tsianos VE, Zois CD, et al. Inflammatory bowel disease and hepatitis B and C in Western Balkans: a referral centre study and review of the literature. J Crohns Colitis. 2010;4:450–465.

    Article  PubMed  Google Scholar 

  23. Chevaux JB, Bigard MA, Bensenane M, et al. Inflammatory bowel disease and hepatitis B and C. Gastroenterol Clin Biol. 2009;33:1082–1093.

    Article  PubMed  Google Scholar 

  24. Shale MJ. The implications of anti-tumour necrosis factor therapy for viral infection in patients with inflammatory bowel disease. Br Med Bull. 2009;92:61–77.

    Article  PubMed  CAS  Google Scholar 

  25. Shale MJ, Seow CH, Coffin CS, et al. Review article: chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel disease. Aliment Pharmacol Ther. 2010;31:20–34.

    Article  PubMed  CAS  Google Scholar 

  26. Horn TL, Reynolds J, de Villiers W, et al. Hepatitis C virus and inflammatory bowel disease. Dig Dis Sci. 2009;54:1171–1177.

    Article  PubMed  Google Scholar 

  27. Biancone L, Pavia M, Del Vecchio Blanco G, et al. Hepatitis B and C virus infection in Crohn’s disease. Inflamm Bowel Dis. 2001;7:287–294.

    Article  PubMed  CAS  Google Scholar 

  28. Loras C, Gisbert JP, Minguez M, et al. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. Gut. 2010;59:1340–1346.

    Article  PubMed  CAS  Google Scholar 

  29. Loras C, Saro C, Gonzalez-Huix F, et al. Prevalence and factors related to hepatitis B and C in inflammatory bowel disease patients in Spain: a nationwide, multicenter study. Am J Gastroenterol. 2009;104:57–63.

    Article  PubMed  CAS  Google Scholar 

  30. Chevaux JB, Nani A, Oussalah A, et al. Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France. Inflamm Bowel Dis. 2010;16:916–924.

    Article  PubMed  Google Scholar 

  31. Alderson JW, Van Dinter TG Jr, Opatowsky MJ, et al. Disseminated aspergillosis following infliximab therapy in an immunosuppressed patient with Crohn’s disease and chronic hepatitis C: a case study and review of the literature. MedGenMed. 2005;7:7.

    PubMed  Google Scholar 

  32. Ferri C, Ferraccioli G, Ferrari D, et al. Safety of anti-tumor necrosis factor-alpha therapy in patients with rheumatoid arthritis and chronic hepatitis C virus infection. J Rheumatol. 2008;35:1944–1949.

    PubMed  CAS  Google Scholar 

  33. Marotte H, Fontanges E, Bailly F, et al. Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus. Rheumatology (Oxford). 2007;46:97–99.

    Article  CAS  Google Scholar 

  34. Peterson JR, Hsu FC, Simkin PA, et al. Effect of tumour necrosis factor alpha antagonists on serum transaminases and viraemia in patients with rheumatoid arthritis and chronic hepatitis C infection. Ann Rheum Dis. 2003;62:1078–1082.

    Article  PubMed  CAS  Google Scholar 

  35. Longo F, Hebuterne X, Tran A, et al. Prevalence of hepatitis C in patients with chronic inflammatory bowel disease in the region of Nice and evaluation of risk factors. Gastroenterol Clin Biol. 2000;24:77–81.

    PubMed  CAS  Google Scholar 

  36. Ray RB, Meyer K, Ray R. Suppression of apoptotic cell death by hepatitis C virus core protein. Virology. 1996;226:176–182.

    Article  PubMed  CAS  Google Scholar 

  37. Ray RB, Meyer K, Steele R, et al. Inhibition of tumor necrosis factor (TNF-alpha)-mediated apoptosis by hepatitis C virus core protein. J Biol Chem. 1998;273:2256–2259.

    Article  PubMed  CAS  Google Scholar 

  38. Tilg H, Kaser A, Moschen AR. How to modulate inflammatory cytokines in liver diseases. Liver Int. 2006;26:1029–1039.

    Article  PubMed  CAS  Google Scholar 

  39. Tilg H, Wilmer A, Vogel W, et al. Serum levels of cytokines in chronic liver diseases. Gastroenterology. 1992;103:264–274.

    PubMed  CAS  Google Scholar 

  40. Gonzalez-Amaro R, Garcia-Monzon C, Garcia-Buey L, et al. Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis. J Exp Med. 1994;179:841–848.

    Article  PubMed  CAS  Google Scholar 

  41. Sandborn WJ, Hanauer SB, Katz S, et al. Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2001;121:1088–1094.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

Dr. Gary R. Lichtenstein has served as a consultant and performed research with Alaven, Jansen Orthobiotech, Proctor and Gamble, Warner Chilcotte, UCB, Prometheus Laboratories, Inc, Salix Pharmaceuticals, Shire Pharmaceuticals, Santarus, Ferring. He has served as a consultant to Abbott Corporation, Elan, Meda, Millenium, Ono Pharmaceuticals. Pfizer, Schering Plough, Wyeth. He has done research with Bristol-Myers Squibb.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gary R. Lichtenstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, M.V., Blonski, W., Buchner, A.M. et al. The Influence of Anti-TNF Therapy on the Course of Chronic Hepatitis C Virus Infection in Patients with Inflammatory Bowel Disease. Dig Dis Sci 58, 1149–1156 (2013). https://doi.org/10.1007/s10620-012-2457-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2457-0

Keywords

Navigation