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Impact of interferon lambda 4 genotype on interferon-stimulated gene expression during direct-acting antiviral therapy for hepatitis C

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Title: Impact of interferon lambda 4 genotype on interferon-stimulated gene expression during direct-acting antiviral therapy for hepatitis C
Authors: Ramamurthy, N
Marchi, E
Ansari, MA
Pedergnana, V
Mclean, A
Hudson, E
Bowden, R
Spencer, CCA
Barnes, E
Klenerman, P
Item Type: Journal Article
Abstract: New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat, including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, patients with cirrhosis receiving a 16‐week course of sofosbuvir and ribavirin had a sustained virological response (SVR) rate of around 50%. In patients with cirrhosis, interferon lambda 4 (IFNL4) CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon‐stimulated gene (ISG) signature in peripheral blood and in liver at baseline. Unexpectedly, patients with the CC genotype showed a dynamic increase in ISG expression between weeks 4 and 16 of DAA therapy, whereas the reverse was true for non‐CC patients. Conclusion: These data provide an important dynamic link between host genotype and phenotype in HCV therapy also potentially relevant to naturally acquired infection.
Issue Date: 30-Sep-2018
Date of Acceptance: 8-Mar-2018
URI: http://hdl.handle.net/10044/1/65471
DOI: https://dx.doi.org/10.1002/hep.29877
ISSN: 0270-9139
Publisher: Wiley
Start Page: 859
End Page: 871
Journal / Book Title: Hepatology
Volume: 68
Issue: 3
Copyright Statement: © 2018 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Medical Research Council (MRC)
National Institute for Health Research
National Institute for Health Research
Funder's Grant Number: MR/K01532X/1
EME/14/02/17
RP-2016-07-012
Keywords: 1103 Clinical Sciences
1101 Medical Biochemistry And Metabolomics
Gastroenterology & Hepatology
Publication Status: Published
Online Publication Date: 2018-09-15
Appears in Collections:Department of Medicine
Faculty of Medicine



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