Peginterferon alfa and ribavirin
The clearest pharmacogenetic story medicine has had, and it is over. Two genotypes told you whether this regimen would work and whether it would make you anaemic — and then better drugs made the question stop mattering.
What this drug connects to
The genes involved
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).
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).
How common these versions are, by ancestry
The share of people who carry at least one copy of each version. For the same medicine, it often differs more than tenfold between groups.
IFNL3 T rs12979860 — linked to a weaker response to interferon treatment for hepatitis C
Worked out from each group's allele frequency: Korean from the Korean studies published in dbSNP, the rest from gnomAD's ancestry groups (via Ensembl), as the survey defines them, not races. How common a version is in a group says nothing about any one person; only a test does.
Whose work this rests on
Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.
Questions about Peginterferon alfa and ribavirin
What are peginterferon alfa and ribavirin?
Peginterferon alfa and ribavirin are an older combination treatment for chronic hepatitis C. Two genotypes once predicted whether this regimen would work and whether it would cause anaemia — and then better drugs made the question largely stop mattering.
Does IFNL3 genotype still matter for hepatitis C treatment with peginterferon alfa today?
Mostly not anymore. IFNL3 (historically IL28B) genotype was the strongest baseline predictor of response to peginterferon alfa and ribavirin, but direct-acting antivirals have since replaced interferon-based regimens for most patients, and where they’re used this genotype’s predictive value largely falls away.
What does the ITPA variant predict for ribavirin treatment?
Not whether ribavirin works, but a specific side effect. Ribavirin causes haemolytic anaemia in most patients, severe enough to require a dose change in up to 15%. Variants causing ITPA deficiency protect against that anaemia.
Quoting this page
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Peginterferon alfa and ribavirin. MyGeneLog™. https://www.mygenelog.com/drugs/peginterferon-ribavirin