Journal Mobile Options
Table of Contents
Vol. 29, No. 2, 2011
Issue release date: July 2011
Dig Dis 2011;29:184–190

Infections and the Liver

Eksteen B.
Centre for Liver Research, MRC Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, and The Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust, Birmingham, UK

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Hepatitis B (HBV) and hepatitis C virus (HCV) have infected nearly half a billion individuals worldwide and are major indications for liver transplantation. Key requirements to successful outcomes with modern antiviral drugs are favourable host factors. Results: Single nucleotide polymorphisms near the IL28B gene location which encode for interferon (IFN)-λ3 have a large effect in determining the likelihood of patients obtaining a cure from pegylated IFN-α and ribavirin combination therapy or spontaneous clearance of the HCV. 80% of patients who carry two copies of this advantageous variant cleared the virus during IFN therapy and remained virus-free with a sustained viral response. This mutation is more common in Caucasian and Asian populations, whereas it is only found in the 40–50% of sub-Saharan Africans who are known to be more resistant to combination therapy. Similarly, host factors control tolerance to chronic HBV infection and can fluctuate over time with increased risk of progression to cirrhosis and particularly liver cancer. Loss of viral tolerance with reactivation and hepatitis is increasingly seen with the widespread use of biological treatments for diseases such as inflammatory bowel disease or rheumatoid arthritis. Natural disasters and conflicts in some parts of the world have also seen an increase in cases of hepatitis A and E virus infection and highlighted the global public health burden from viral-induced hepatitis. Conclusions: Increased appreciation of the interaction between host factors and the viral life cycles is likely to significantly alter the way we target these infections in the future.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH: Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000;132:296–305.
  2. McHutchison JG, Lawitz EJ, Shiffman ML, et al: Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009;361:580–593.
  3. Thompson AJ, Muir AJ, Sulkowski MS, et al: Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139:120–129.
  4. Myers RP, Patel K, Pianko S, Poynard T, McHutchison JG: The rate of fibrosis progression is an independent predictor of the response to antiviral therapy in chronic hepatitis C. J Viral Hepat 2003;10:16–22.
  5. Teoh NC, Farrell GC, Chan HL: Individualisation of antiviral therapy for chronic hepatitis C. J Gastroenterol Hepatol 2010;25:1206–1216.
  6. Parikh M, Singh A, Sood G: Extended treatment duration for treatment naive chronic hepatitis C genotype 1 late viral responders: a meta-analysis comparing 48 weeks vs. 72 weeks of pegylated interferon and ribavirin. J Viral Hepat 2010 (in press).
  7. Ferenci P, Laferl H, Scherzer TM, et al: Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response. Gastroenterology 2010;138:503–512, 12e1.
  8. Ge D, Fellay J, Thompson AJ, et al: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399–401.
  9. Thomas DL, Thio CL, Martin MP, et al: Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009;461:798–801.
  10. 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 virologic response. Gastroenterology 2010;139:821–827, 7e1.
  11. Suppiah V, Moldovan M, Ahlenstiel G, et al: IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nat Genet 2009;41:1100–1104.
  12. Tanaka Y, Nishida N, Sugiyama M, et al: Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nat Genet 2009;41:1105–1109.
  13. Li M, Liu X, Zhou Y, Su SB: Interferon-λs: the modulators of antivirus, antitumor, and immune responses. J Leukoc Biol 2009;86:23–32.
  14. O’Brien TR: Interferon-alfa, interferon-λ and hepatitis C. Nat Genet 2009;41:1048–1050.
  15. 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 2010;139:1586–1592, e1.
  16. Ma D, Jiang D, Qing M, et al: Antiviral effect of interferon lambda against West Nile virus. Antiviral Res 2009;83:53–60.
  17. Clark PJ, Thompson AJ, McHutchison JG: IL28B genomic-based treatment paradigms for patients with chronic hepatitis C infection: the future of personalized HCV therapies. Am J Gastroenterol 2011;106:38–45.
  18. Balagopal A, Thomas DL, Thio CL: IL28B and the control of hepatitis C virus infection. Gastroenterology 2010;139:1865–1876.
  19. Schinazi RF, Bassit L, Gavegnano C: HCV drug discovery aimed at viral eradication. J Viral Hepat 2010;17:77–90.
  20. Thompson AJ, McHutchison JG: Investigational agents for chronic hepatitis C. Aliment Pharmacol Ther 2009;29:689–705.
  21. Georgel P, Schuster C, Zeisel MB, et al: Virus-host interactions in hepatitis C virus infection: implications for molecular pathogenesis and antiviral strategies. Trends Mol Med 2010;16:277–286.
  22. Stamataki Z, Grove J, Balfe P, McKeating JA: Hepatitis C virus entry and neutralization. Clin Liver Dis 2008;12:693–712, x.
  23. Lindenbach BD, Evans MJ, Syder AJ, et al: Complete replication of hepatitis C virus in cell culture. Science 2005;309:623–626.
  24. Evans MJ, von HT, Tscherne DM, et al: Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007;446:801–805.
  25. Grove J, Huby T, Stamataki Z, et al: Scavenger receptor BI and BII expression levels modulate hepatitis C virus infectivity. J Virol 2007;81:3162–3169.
  26. Zhang J, Randall G, Higginbottom A, Monk P, Rice CM, McKeating JA: CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. J Virol 2004;78:1448–1455.
  27. Fofana I, Krieger SE, Grunert F, et al: Monoclonal anti-claudin-1 antibodies prevent hepatitis C virus infection of primary human hepatocytes. Gastroenterology 2010;139:953–964, e1–e4.
  28. Brimacombe CL, Grove J, Meredith LW, et al: Neutralizing antibody resistant hepatitis C virus cell-to-cell transmission. J Virol 2011;85:596–605.
  29. Timpe JM, McKeating JA: Hepatitis C virus entry: possible targets for therapy. Gut 2008;57:1728–1737.
  30. Timpe JM, Stamataki Z, Jennings A, et al: Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 2008;47:17–24.
  31. Webster DP, Klenerman P, Collier J, Jeffery KJ: Development of novel treatments for hepatitis C. Lancet Infect Dis 2009;9:108–117.
  32. McHutchison JG, Everson GT, Gordon SC, et al: Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009;360:1827–1838.
  33. European Association for the Study of the Liver: EASL clinical practice guidelines. Management of chronic hepatitis B (in French). Gastroenterol Clin Biol 2009;33:539–554.
  34. Okuda K: Hepatocellular carcinoma. J Hepatol 2000;32:225–237.
  35. Ge J, Wang K, Meng QH, Qi ZX, Meng FL, Fan YC: Implication of Th17 and Th1 cells in patients with chronic active hepatitis B. J Clin Immunol 2010;30:60–67.
  36. Liaw YF, Sheen IS, Lee CM, et al: Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology 2010 (in press).
  37. Heo NY, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ: Lamivudine plus adefovir or entecavir for patients with chronic hepatitis B resistant to lamivudine and adefovir. J Hepatol 2010;53:449–954.
  38. Hann HW: Telbivudine: an effective anti-HBV drug for chronic hepatitis B patients with early on-treatment responses. Expert Opin Pharmacother 2010;11:2243–2249.
  39. Woo G, Tomlinson G, Nishikawa Y, et al: Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and bayesian meta-analyses. Gastroenterology 2010;139:1218–1229.
  40. Locarnini S, Hatzakis A, Heathcote J, et al: Management of antiviral resistance in patients with chronic hepatitis B. Antivir Ther 2004;9:679–693.
  41. Zhang WX, Lai V, Mutimer D, Mirza D: Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatobiliary Pancreat Dis Int 2006;5:154–156.

    External Resources

  42. Katz LH, Tur-Kaspa R, Guy DG, Paul M: Lamivudine or adefovir dipivoxil alone or combined with immunoglobulin for preventing hepatitis B recurrence after liver transplantation. Cochrane Database Syst Rev 2010: CD006005.
  43. Jimenez-Perez M, Saez-Gomez AB, Mongil Poce L, Lozano-Rey JM, de la Cruz-Lombardo J, Rodrigo-Lopez JM: Efficacy and safety of entecavir and/or tenofovir for prophylaxis and treatment of hepatitis B recurrence post-liver transplant. Transplant Proc 2010;42:3167–3168.
  44. Chen J, Yi L, Jia JD, Ma H, You H: Hepatitis B immunoglobulins and/or lamivudine for preventing hepatitis B recurrence after liver transplantation: a systematic review. J Gastroenterol Hepatol 2010;25:872–879.
  45. Rehermann B, Nascimbeni M: Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005;5:215–229.
  46. Simonetti J, Bulkow L, McMahon BJ, et al: Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 2010;51:1531–1537.
  47. Coffin CS, Fraser HF, Panaccione R, Ghosh S: Liver diseases associated with anti-tumor necrosis factor-α use for inflammatory bowel disease. Inflamm Bowel Dis 2010.
  48. Shale J, Seow H, Coffin S, Kaplan G, Panaccione R, Ghosh S: Chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel disease. Aliment Pharmacol Ther 2010;31:20–34.
  49. Hamaki T, Kami M, Kusumi E, et al: Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab. Am J Hematol 2001;68:292–294.
  50. Meng XJ: Recent advances in hepatitis E virus. J Viral Hepat 2010;17:153–161.
  51. Labrique AB, Zaman K, Hossain Z, et al: Epidemiology and risk factors of incident hepatitis E virus infections in rural Bangladesh. Am J Epidemiol 2010;172:952–961.
  52. Ippagunta SK, Naik S, Sharma B, Aggarwal R: Presence of hepatitis E virus in sewage in Northern India: frequency and seasonal pattern. J Med Virol 2007;79:1827–1831.
  53. Xia H, Wahlberg N, Belak S, Meng XJ, Liu L: The emergence of genotypes 3 and 4 hepatitis E virus in swine and humans: a phylogenetic perspective. Arch Virol 2011;156:121–124.
  54. Colson P, Borentain P, Queyriaux B, et al: Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis 2010;202:825–834.
  55. Rolfe KJ, Curran MD, Mangrolia N, et al: First case of genotype-4 human hepatitis E virus infection acquired in India. J Clin Virol 2010;48:58–61.
  56. Leblanc D, Poitras E, Gagne MJ, Ward P, Houde A: Hepatitis E virus load in swine organs and tissues at slaughterhouse determined by real-time RT-PCR. Int J Food Microbiol 2010;139:206–209.
  57. Masia G, Orru G, Liciardi M, et al: Evidence of hepatitis E virus infection in human and pigs in Sardinia, Italy. J Prev Med Hyg 2009;50:227–231.
  58. McCreary C, Martelli F, Grierson S, Ostanello F, Nevel A, Banks M: Excretion of hepatitis E virus by pigs of different ages and its presence in slurry stores in the United Kingdom. Vet Rec 2008;163:261–265.
  59. Billerbeck E, Kang YH, Walker L, et al: Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA 2010;107:3006–3011.
  60. Lee YH, Ha Y, Ahn KK, Chae C: Localisation of swine hepatitis E virus in experimentally infected pigs. Vet J 2009;179:417–421.
  61. De Deus N, Seminati C, Pina S, Mateu E, Martin M, Segales J: Detection of hepatitis E virus in liver, mesenteric lymph node, serum, bile and faeces of naturally infected pigs affected by different pathological conditions. Vet Microbiol 2007;119:105–114.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50