Peginterferon alfa-2a

Interferon alfa is a signaling protein that switches on the body's antiviral defenses. In peginterferon, a polyethylene glycol chain is attached so the drug lasts long enough for once-weekly injections under the skin. The Pegasys label describes it as an inducer of the innate immune response [2].

Before 2011, chronic hepatitis C was treated with peginterferon and ribavirin for 24 weeks (hepatitis C virus genotypes 2 and 3) or 48 weeks (other genotypes). From 2011, the protease inhibitors boceprevir and telaprevir were added for genotype 1. Cure is measured as a sustained virologic response (SVR): no detectable virus 12 to 24 weeks after treatment ends [1].

The current Pegasys label still lists chronic hepatitis C, in combination with other hepatitis C drugs, and chronic hepatitis B. It allows peginterferon alone for hepatitis C only when other drugs cannot be used. Its boxed warning covers fatal or life-threatening neuropsychiatric, autoimmune, ischemic and infectious disorders, and when used with ribavirin it carries ribavirin's risk of birth defects [2].

IFNL3 (formerly IL28B) makes interferon lambda 3, an antiviral signaling protein whose receptor is found mainly on liver and other epithelial cells. Four genome-wide studies linked variants near IFNL3 to cure of hepatitis C with peginterferon and ribavirin. The two variants tested most often, rs12979860 and rs8099917, lie close together and are usually inherited together. How they change the response is still not well understood [1]. Gene2Rx reads rs12979860.

CPIC classes rs12979860 CC as the favorable response genotype and CT or TT as unfavorable [1]. In the original discovery cohort, White patients with CC were much more likely to clear the virus early (28% had undetectable virus by week 4, against 5% for CT and TT) and to be cured (69%, against 33% and 27%). Similar patterns were seen in Hispanic and African American patients. Overall, the favorable genotype was associated with about twice the cure rate in hepatitis C genotype 1 [1].

The favorable C allele differs by ancestry: its frequency is close to 0.9 in East Asian, 0.63 in White, 0.55 in Hispanic and 0.39 in African-origin populations, which largely explains differences in treatment response between these groups [1]. The Pegasys label itself notes that IL28B variants affect the response and says genotyping should be considered [2].

The genotype mattered less in some settings. It did not predict response in hepatitis C genotypes 2 and 3, or in patients who had already failed interferon treatment. It was also linked to spontaneous clearance of new (acute) infections: 53% of people with CC cleared the virus on their own, against 28% with CT or TT [1].

CPIC published its IFNL3 guideline in 2014 to support shared decisions about starting peginterferon-based treatment for hepatitis C genotype 1. It did not change doses; it gave the expected chance of cure for each genotype, with and without a protease inhibitor [1]. On May 13, 2026, CPIC marked the peginterferon guideline pairs as retired [3]. The table shows what the guideline said, which is also what the Gene2Rx report shows.

For most people with hepatitis C, an IFNL3 result no longer affects treatment. US guidance from AASLD and IDSA is built around DAA regimens, such as glecaprevir/pibrentasvir, and describes DAA therapy as having a cure rate above 95% [4]. If you have hepatitis C, the choice of regimen depends on the virus genotype, liver health, past treatment and other medicines, not on IFNL3.

The result can still be of interest. The same guidance lists variants near IL28B among factors linked to spontaneous clearance of a new infection [4]. Peginterferon alfa-2a is also used for chronic hepatitis B [2], but CPIC's IFNL3 guidance covered hepatitis C only. Do not start, stop or change any medicine because of a genetic result without talking to your clinician.

An IFNL3 genotype was always one factor among many. CPIC lists others linked to cure with interferon: hepatitis C genotypes 2 and 3, lower viral load, younger age, female sex, less liver scarring, no insulin resistance and lower body mass index [1]. In the boceprevir trials, once the response to the first 4 weeks of treatment was known, genotype no longer added to the prediction.

Consumer arrays (23andMe, AncestryDNA, MyHeritage) are not clinical-grade tests, and their raw data is labeled not for medical use. Gene2Rx reads rs12979860 from the uploaded file, directly or by imputation. CPIC noted that rs12979860 was less reliable than rs8099917 for predicting response in Japanese patients [1].

I have the unfavorable genotype. Will hepatitis C treatment work for me?

The unfavorable genotype predicted lower cure rates with interferon-based treatment. Current DAA treatment is not chosen by IFNL3 genotype (see Using your result today).

Why is this guideline still in my report?

Peginterferon alfa-2a is still an approved medicine, and the IFNL3 result is real. The report keeps the historical guidance so the result is explained, but CPIC no longer maintains it.

1. Muir AJ, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-alpha-based regimens. Clin Pharmacol Ther (2014). Evidence, cure rates by genotype and recommendations.
2. Pegasys (peginterferon alfa-2a) injection: prescribing information (pharmaand). DailyMed. Indications, boxed warning and IL28B statement.
3. CPIC. Gene-drug pairs and CPIC levels (spreadsheet). Peginterferon pairs listed as retired; change log entry dated May 13, 2026.
4. Ghany MG, et al. Hepatitis C guidance 2019 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology (2020). Direct-acting antiviral treatment.