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Innate immune response contributes to HCV clearance with DAAs

Interferon-experienced patients with hepatitis C who achieved sustained virologic response with direct-acting antivirals were more likely to have a higher baseline expression of interferon-stimulated genes compared with those who experienced a virologic breakthrough, according to a recently published study.

“Our results suggest that the innate immune response may contribute to viral clearance with an interferon-free regimen,” Hawwa Alao, MD, from the National Institutes of Health in Bethesda, Md., and colleagues wrote. “We speculate that this innate immune response may prevent the emergence of resistance-associated substitutions that lead to viral breakthrough during DAA therapy.”

Alao and colleagues enrolled 13 patients with HCV genotype 1b who had previous partial or no response to pegylated interferon with ribavirin therapy. Twelve patients had the rs12979860-CT or -TT allele and twelve patients had the rs368234815-delta G genetic variant, both of which are associated with an unfavorable response to interferon treatment.

Compared with baseline, the researchers found 408 genes that were differently expressed in biopsies taken during treatment (P < .01). Most of the aberrantly expressed genes were downregulated during therapy and most of the significantly downregulated cellular pathways were interferon signaling pathways, particularly those related to production of interferon-stimulated genes (ISG).

The researchers also found that genes involved in mitochondrial and metabolic pathways were enriched among pathways that were upregulated during DAA therapy.

“Our results extend the published data and suggest that viral replication is the inducer of high ISG expression,” Alao and colleagues wrote. “ISG expression data from the initial 72 hours, when there is the greatest decline in HCV RNA levels, would have provided stronger evidence. Unfortunately, we were unable to perform a third biopsy at this early treatment timepoint.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.