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http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract & ArtikelNr=\

323884 & Ausgabe=255156 & ProduktNr=224231

Infections and the Liver

Bertus Eksteen

Centre for Liver Research, MRC Centre for Immune Regulation, Institute for

Biomedical Research, Medical School, University of Birmingham, and The Queen

Hospital, University Hospitals Birmingham NHS Trust, Birmingham, UK

Address of Corresponding Author

Dig Dis 2011;29:184-190 (DOI: 10.1159/000323884)

Abstract

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)-ë3 have a large effect in determining the likelihood

of patients obtaining a cure from pegylated IFN-á 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 © 2011 S. Karger AG, Basel

--------------------------------------------------------------------------------

Author Contacts

Dr. Bertus Eksteen

Centre for Liver Research and NIHR Biomedical Research Unit

MRC Centre for Immune Regulation, Institute for Biomedical Research

University of Birmingham, Drive, Edgbaston, Birmingham B15 2TT (UK)

Tel. +44 121 415 8700, E-Mail b.eksteen@...

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Guest guest

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract & ArtikelNr=\

323884 & Ausgabe=255156 & ProduktNr=224231

Infections and the Liver

Bertus Eksteen

Centre for Liver Research, MRC Centre for Immune Regulation, Institute for

Biomedical Research, Medical School, University of Birmingham, and The Queen

Hospital, University Hospitals Birmingham NHS Trust, Birmingham, UK

Address of Corresponding Author

Dig Dis 2011;29:184-190 (DOI: 10.1159/000323884)

Abstract

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)-ë3 have a large effect in determining the likelihood

of patients obtaining a cure from pegylated IFN-á 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 © 2011 S. Karger AG, Basel

--------------------------------------------------------------------------------

Author Contacts

Dr. Bertus Eksteen

Centre for Liver Research and NIHR Biomedical Research Unit

MRC Centre for Immune Regulation, Institute for Biomedical Research

University of Birmingham, Drive, Edgbaston, Birmingham B15 2TT (UK)

Tel. +44 121 415 8700, E-Mail b.eksteen@...

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