For a few years this was the pharmacogenomic test people actually ordered: it predicted who would respond to interferon. Then the drugs changed, and a marker that once decided treatment became a historical curiosity. That is the most useful thing this page has to say.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Hepatitis C is a virus that infects the liver. Most people who catch it do not clear it — the virus establishes a chronic infection in 50% to 80% of those infected — and decades of chronic infection can cause cirrhosis and liver cancer. It is also, now, curable in the large majority of people.
The genetics here is unusually clean. A 2010 genome-wide study of 1,362 people — 1,015 with chronic infection and 347 who cleared the virus on their own — found the answer sitting in the IL28B region, which encodes interferon lambda, an antiviral signalling molecule.
The minor allele of rs8099917 was associated with progressing to chronic infection rather than clearing it, with an odds ratio of 2.31 (95% CI 1.74–3.06). That is a large effect for a common variant — larger than almost anything on the cancer pages of this site — and it makes biological sense: a weaker interferon response, a virus that establishes itself.
The same study assessed response to pegylated interferon alfa and ribavirin in 465 people, and the same region predicted that too. For a while this was genuinely practice-changing. Interferon treatment was long, unpleasant — flu-like illness for months — and failed in roughly half of patients. A test that told you in advance whether it was likely to work was worth having, and IL28B genotyping entered clinical use.
Then direct-acting antivirals arrived. They cure the great majority of people in eight to twelve weeks with few side effects, and they do it largely regardless of this genotype. The test that mattered stopped mattering — not because the finding was wrong, but because the question it answered went away.
That is worth stating plainly on a site about genetics: a genetic marker's value depends on the medicine of its moment. This one was real, useful, and is now mostly of historical interest, and the same will be true of markers this site describes today.
Being tested. Hepatitis C is often silent for decades, treatment is short and works, and the people most likely to have it are frequently the least likely to have been offered a test. If you have ever injected drugs, had a transfusion before blood screening, been born to a mother with hepatitis C, or had a medical or tattoo procedure with unsterile equipment, a test is the useful step — not a genotype.
Nothing on this page changes eligibility for treatment, and nobody should read a variant here as a reason to think they cannot be cured.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 1 more position to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Ishigaki K et al. 2020, Nature genetics rs8113007 (near MSRB1P1) — PMID:32514122
The study. Rauch et al. analysed more than 500,000 SNPs in 1,362 individuals: 1,015 with chronic hepatitis C and 347 who had spontaneously cleared the virus, of whom 448 were coinfected with HIV. Responses to pegylated interferon alfa and ribavirin were assessed in 465. Chronic infection was associated with SNPs in the IL28B locus, which encodes interferon lambda 3; the rs8099917 minor allele carried an odds ratio of 2.31 (95% CI 1.74–3.06) for progression to chronic infection.
IFNL4. Later work identified a frameshift variant creating the IFNL4 open reading frame in the same region, in strong linkage disequilibrium with the IL28B markers, as a stronger candidate for the causal variant. The association reported here is to a marker in that haplotype rather than to a demonstrated causal allele — the usual situation, and worth stating rather than implying otherwise.
Clinical status. IL28B genotyping had a genuine role in the interferon era, where sustained virological response rates were roughly 50% for genotype 1 infection and treatment lasted 24–48 weeks with substantial toxicity. Direct-acting antiviral regimens achieve sustained virological response in the large majority of patients across genotypes, and current guidelines do not use IL28B or any host genotype to select therapy. Testing decisions rest on exposure history and, increasingly, on universal screening recommendations in adults.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Chronic Hepatitis C comes down to these specific, well-studied positions — not a diagnosis.
HLA-DQA1 · rs9461776
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 8 of 9 linked studies with a resolved discovery ancestry.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| IFNL3 | Peginterferon alfa and ribavirin | IFNL3 (historically IL28B) genotype is the strongest baseline predictor of response to peginterferon alfa and ribavirin in previously untreated hepatitis C, and CPIC published a guideline for using it as part of the shared decision to start that treatment. The context matters as much as the association: direct-acting antivirals have since replaced interferon-based regimens for most patients, and where they are used the predictive value of this genotype largely falls away. This is a pharmacogenetic marker that was close to standard of care and was overtaken by better drugs rather than by better genetics. (CPIC guidelines for IFNL3 (IL28B) genotype and PEG interferon-α-based regimens (Clin Pharmacol Ther 2014, PMID 24096968).) |
| ITPA | Peginterferon alfa and ribavirin | Ribavirin causes haemolytic anaemia in most patients who take it, severe enough to require a dose change in up to 15%. Variants causing inosine triphosphatase deficiency — a condition that had not been thought clinically important — protect against it. This is the unusual case of a genetic deficiency turning out to be an advantage in a specific pharmacological situation, and it predicts a side effect rather than whether the drug works. (Fellay et al., Nature 2010 — ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C (PMID 20173735).) |
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Chronic Hepatitis C. MyGeneLog™. https://www.mygenelog.com/conditions/chronic-hepatitis-c
No. Modern direct-acting antivirals cure the great majority of people regardless of this genotype. The variant mattered when treatment was interferon-based; that era has largely ended.
Because it is the clearest example on this site of something true and temporary. A genetic test can be genuinely useful and then become irrelevant, not because the science was wrong but because the medicine improved. Markers described here today can end the same way.
That is a question for a clinician and it does not depend on genetics. Infection is often silent for decades and the treatment is short and effective, so the value of testing is high for anyone with a plausible exposure — and many countries now recommend testing adults regardless.
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