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

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.