Liver gene expression profiles correlate with virus infection and response to interferon therapy in chronic hepatitis B patients

Hui Lin Wu, Tzu Hung Hsiao, Pei Jer Chen, Siao Han Wong, Jia Horng Kao, Ding Shinn Chen, Jo Yang Lu, Tzu Pin Lu, Yidong Chen, Eric Y. Chuang, Hui Chu Tu, Chun Jen Liu

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Abstract

The natural course of chronic hepatitis B (CHB) infection and treatment response are determined mainly by the genomic characteristics of the individual. We investigated liver gene expression profiles to reveal the molecular basis associated with chronic hepatitis B and IFN-alpha (IFNα) treatment response in CHB patients. Expression profiles were compared between seven paired liver biopsy samples taken before and 6 months after successful IFNα treatment or between pretreatment biopsy samples of 11 IFNα responders and 11 non-responders. A total of 132 differentially up-regulated and 39 down-regulated genes were identified in the pretreated livers of CHB patients. The up-regulated genes were mainly related to cell proliferation and immune response, with IFNγ 3 and B cell signatures significantly enriched. Lower intrahepatic HBV pregenomic RNA levels and 25 predictive genes were identified in IFNα responders. The predictive gene set in responders significantly overlapped with the up-regulated genes associated with the pretreated livers of CHB patients. The mechanisms responsible for IFNα treatment responses are different between HBV and HCV patients. HBV infection evokes significant immune responses even in chronic infection. The up-regulated genes are predictive of responsiveness to IFNα therapy, as are lower intrahepatic levels of HBV pregenomic RNA and pre-activated host immune responses.

Original languageEnglish (US)
Article number31349
JournalScientific Reports
Volume6
DOIs
StatePublished - Aug 22 2016

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Chronic Hepatitis B
Virus Diseases
Transcriptome
Interferons
Liver
Genes
Therapeutics
Infection
RNA
Biopsy
B-Lymphocytes
Cell Proliferation

ASJC Scopus subject areas

  • General

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Liver gene expression profiles correlate with virus infection and response to interferon therapy in chronic hepatitis B patients. / Wu, Hui Lin; Hsiao, Tzu Hung; Chen, Pei Jer; Wong, Siao Han; Kao, Jia Horng; Chen, Ding Shinn; Lu, Jo Yang; Lu, Tzu Pin; Chen, Yidong; Chuang, Eric Y.; Tu, Hui Chu; Liu, Chun Jen.

In: Scientific Reports, Vol. 6, 31349, 22.08.2016.

Research output: Contribution to journalArticle

Wu, HL, Hsiao, TH, Chen, PJ, Wong, SH, Kao, JH, Chen, DS, Lu, JY, Lu, TP, Chen, Y, Chuang, EY, Tu, HC & Liu, CJ 2016, 'Liver gene expression profiles correlate with virus infection and response to interferon therapy in chronic hepatitis B patients', Scientific Reports, vol. 6, 31349. https://doi.org/10.1038/srep31349
Wu, Hui Lin ; Hsiao, Tzu Hung ; Chen, Pei Jer ; Wong, Siao Han ; Kao, Jia Horng ; Chen, Ding Shinn ; Lu, Jo Yang ; Lu, Tzu Pin ; Chen, Yidong ; Chuang, Eric Y. ; Tu, Hui Chu ; Liu, Chun Jen. / Liver gene expression profiles correlate with virus infection and response to interferon therapy in chronic hepatitis B patients. In: Scientific Reports. 2016 ; Vol. 6.
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