Hepatitis C treatment response (IL28B)

This variant near the interferon-lambda genes strongly predicts how well older interferon-based hepatitis C treatment works, and how likely the body is to clear a hepatitis C infection on its own. The favorable 'C' version is good news.

What this variant does

This variant sits next to IFNL4, a gene in the interferon lambda family, part of the antiviral response. It is a marker for whether a functional IFNL4 protein is produced, and counterintuitively, the version that produces the protein is the one associated with worse outcomes in hepatitis C.

The favourable genotype is associated both with clearing hepatitis C spontaneously after infection and, historically, with responding to interferon-based treatment.

Why this result matters much less than it did

When this association was found in 2009 it was genuinely important. Interferon and ribavirin treatment lasted up to a year, was poorly tolerated, and cured only around half of people with genotype 1 hepatitis C, so predicting who would respond had real clinical value, and this marker was among the strongest predictors available.

Direct-acting antiviral drugs changed that completely. Modern regimens cure well over 95% of people in eight to twelve weeks with few side effects, and they work regardless of this genotype. The marker is now largely of historical and research interest, and no current treatment decision uses it.

How strong the evidence is

The original association was strong for its era: an odds ratio of about 2 for chronic infection in a study of 1,137 people with a p-value below 1e-28, and ClinVar records it as a drug-response variant with three-star review status specifically for peginterferon and ribavirin efficacy, which is exactly the therapy that has been superseded.

An ancestry pattern with a history attached

The favourable genotype is common in East Asian populations and much less common in African-ancestry populations: in 1000 Genomes reference data about 37% of African-ancestry individuals carry two copies of the unfavourable allele against roughly 8% of European-ancestry individuals.

That distribution helped explain a long-standing clinical observation, that African-American patients responded less well to interferon-based hepatitis C therapy, and it reframed a difference that had previously been attributed to other causes. The gap disappeared with direct-acting antivirals, which is a useful reminder that a genetic difference in drug response can be an artefact of the drug rather than a fixed fact about people.

What each rs12979860 genotype means

rs12979860 has three possible genotypes: CC, CT and TT.

Favorable HCV response (IL28B) (rs12979860 CC). You have two copies of the favorable 'C' version near the interferon-lambda genes, linked to a better response to older interferon-based hepatitis C treatment and a higher chance of clearing hepatitis C on your own. This mainly matters in the context of a hepatitis C infection.

Intermediate HCV response (rs12979860 CT). You carry one favorable and one less-favorable copy of the IL28B region, an intermediate predictor of response to interferon-based hepatitis C treatment. Today's hepatitis C drugs (direct-acting antivirals) work well regardless, so this is mostly of historical and academic interest now.

Lower HCV treatment response (IL28B) (rs12979860 TT). You have two copies of the less-favorable version near the interferon-lambda genes, linked to a poorer response to older interferon-based hepatitis C treatment and lower spontaneous clearance. It only matters with a hepatitis C infection, and today's direct-acting antiviral drugs are highly effective regardless of this gene.

Evidence & sources

Across global populations, about 11% of people carry two copies of this variant, and about 49% carry none.

This variant appears in 2 published genetic studies: PubMed 19684573 · PubMed 23420232.

Common questions

Does this affect my hepatitis C treatment today? No. Direct-acting antivirals cure more than 95% of people regardless of this genotype, and treatment decisions do not use it. It mattered in the interferon era, which has ended.

Does the favourable genotype mean I cannot get chronic hepatitis C? No. It is associated with a better chance of clearing the virus spontaneously after exposure, not immunity, and hepatitis C is now curable in nearly everyone who is diagnosed and treated.

Related

Abacavir hypersensitivity (HLA-B*57:01) · Drug acetylation speed (NAT2) · Efavirenz / drug metabolism (CYP2B6*6) · Fluoropyrimidine (5-FU) toxicity risk · Statin-induced myopathy risk · Tacrolimus metabolism (CYP3A5 gene) · Warfarin dose sensitivity