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.
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.
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.
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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