Impact of Interferon Lambda 4 Genotype on Interferon‐Stimulated Gene Expression During Direct‐Acting Antiviral Therapy for Hepatitis C

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...

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Published inHepatology (Baltimore, Md.) Vol. 68; no. 3; pp. 859 - 871
Main Authors Ramamurthy, Narayan, Marchi, Emanuele, Ansari, M. Azim, Pedergnana, Vincent, Mclean, Angela, Hudson, Emma, Bowden, Rory, Spencer, Chris C.A., Barnes, Eleanor, Klenerman, Paul
Format Journal Article
LanguageEnglish
Published United States Wolters Kluwer Health, Inc 01.09.2018
Wiley-Blackwell
John Wiley and Sons Inc
Subjects
Antiviral Agents
Antiviral Agents - therapeutic use
Antiviral drugs
Cirrhosis
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genotype
Genotype & phenotype
Genotypes
Hepatitis
Hepatitis C
Hepatitis C - blood
Hepatitis C - drug therapy
Hepatitis C - genetics
Hepatology
Human health and pathology
Humans
Interferon
Interleukins
Interleukins - genetics
Life Sciences
Liver
Liver - metabolism
Liver Cirrhosis
Liver Cirrhosis - virology
Original
Peripheral blood
Phenotypes
Ribavirin
Ribavirin - therapeutic use
Sofosbuvir
Sofosbuvir - therapeutic use
Sustained Virologic Response
Online AccessGet full text
ISSN0270-9139
1527-3350
1527-3350
DOI10.1002/hep.29877

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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. (Hepatology 2018; 00:000‐000).
AbstractList 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. (H epatology 2018; 00:000‐000).
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. (Hepatology 2018; 00:000‐000).
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. (H epatology 2018; 00:000‐000).
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. (Hepatology 2018; 00:000-000).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. (Hepatology 2018; 00:000-000).
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 interferonstimulated 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. (Hepatology 2018; 68:859-871).
Author Klenerman, Paul
Spencer, Chris C.A.
Barnes, Eleanor
Marchi, Emanuele
Bowden, Rory
Ansari, M. Azim
Hudson, Emma
Pedergnana, Vincent
Mclean, Angela
Ramamurthy, Narayan
AuthorAffiliation 4 Department of Zoology University of Oxford Oxford United Kingdom
2 Wellcome Trust Centre for Human Genetics University of Oxford Oxford United Kingdom
1 Peter Medawar Building for Pathogen Research and Translational Gastroeneterology Unit, Nuffield Department of Medicine University of Oxford Oxford United Kingdom
3 Oxford Martin School University of Oxford Oxford United Kingdom
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– name: 1 Peter Medawar Building for Pathogen Research and Translational Gastroeneterology Unit, Nuffield Department of Medicine University of Oxford Oxford United Kingdom
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Notes The copyright for this article was changed on May 29, 2019, after original online publication.
These authors contributed equally to the work.
Potential conflict of interest: Nothing to report.
This work was funded by a grant from the Medical Research Council (MRC) (MR/K01532X/1; to the STOP‐HCV Consortium). The work was supported by the Wellcome Trust Fund WT109965MA, NIH (U19AI082630), and NIHR Senior Fellowship to P.K. and the NIHR Biomedical Research Centre, Oxford.
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Snippet 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...
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StartPage 859
SubjectTerms Antiviral Agents
Antiviral Agents - therapeutic use
Antiviral drugs
Cirrhosis
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genotype
Genotype & phenotype
Genotypes
Hepatitis
Hepatitis C
Hepatitis C - blood
Hepatitis C - drug therapy
Hepatitis C - genetics
Hepatology
Human health and pathology
Humans
Interferon
Interleukins
Interleukins - genetics
Life Sciences
Liver
Liver - metabolism
Liver Cirrhosis
Liver Cirrhosis - virology
Original
Peripheral blood
Phenotypes
Ribavirin
Ribavirin - therapeutic use
Sofosbuvir
Sofosbuvir - therapeutic use
Sustained Virologic Response
Title Impact of Interferon Lambda 4 Genotype on Interferon‐Stimulated Gene Expression During Direct‐Acting Antiviral Therapy for Hepatitis C
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhep.29877
https://www.ncbi.nlm.nih.gov/pubmed/29534310
https://www.proquest.com/docview/2104158928
https://www.proquest.com/docview/2013784698
https://hal.science/hal-03684796
https://pubmed.ncbi.nlm.nih.gov/PMC6207923
Volume 68
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