Hepatic cell-type specific gene expression better predicts HCV treatment outcome than IL28B genotype

Ian McGilvray ¹, Jordan J Feld , Limin Chen

⁰University Health Network, Toronto, Ontario, Canada.

Gastroenterology +

|

January 31, 2012

View abstract on PubMed

Summary

Cell-type specific interferon-stimulated gene (ISG) patterns in the liver, influenced by IL28B genotype, predict treatment response in chronic hepatitis C. Macrophage ISG expression is a key indicator of treatment outcomes.

Area Of Science

Hepatology
Immunology
Genetics

Background

Interferon-stimulated genes (ISGs) and IL28B single nucleotide polymorphisms (SNPs) are linked to hepatitis C virus (HCV) treatment response.
The interplay between IL28B genotype, ISG expression patterns, and treatment outcomes remains unclear.

Purpose Of The Study

To investigate how IL28B genotype influences hepatic ISG expression.
To determine which factor, IL28B genotype or ISG expression pattern, better predicts response to interferon-based therapy for HCV.

Main Methods

Analysis of hepatic gene expression profiles using cDNA microarrays.
Genotyping of the IL28B SNP rs12979860.
Immunostaining for human myxovirus protein A (MxA) in hepatocytes and macrophages.

Main Results

ISG expression in hepatic macrophages inversely correlated with hepatocytes and strongly predicted treatment outcome.
Absence of MxA staining in macrophages accurately predicted nonresponse (NPV 98%).
IL28B genotype strongly correlated with cell-specific MxA staining, but macrophage MxA presence was a more robust predictor of treatment response.

Conclusions

Cell-type-specific ISG expression patterns vary with IL28B genotype in chronic hepatitis C patients.
Hepatic MxA expression in macrophages is a powerful predictor of response to interferon-based therapy.
The IL28B genotype's predictive value is diminished when macrophage MxA staining is considered.

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