IL28 Genotype

Patients with hepatitis C virus infections are treated with antiviral medications such as pegylated interferon plus ribavirin. The treatment goal is to achieve a sustained virologic response (SVR), which is defined as the absence of HCV RNA by polymerase chain reaction (PCR) six months after stopping treatment. SVR is associated with a 99 percent chance of remaining HCV RNA negative during long-term follow-up. SVR is also associated with decreases in all-cause mortality, liver-related death, the need for liver transplantation, and the risk of hepatocellular carcinoma.

Two of the most important predictors of a sustained virologic response (SVR) following combination therapy with peginterferon plus ribavirin are HCV genotype and baseline viral load. Higher response rates are seen in patients with genotypes 2 or 3 than in those with genotype 1. Higher response rates are seen in those with lower baseline viral loads (≤800,000 IU/mL). 

Patient-related factors that are associated with SVR  include race, age, and IL28B polymorphisms. The highest response rates are seen in Asians, followed by Caucasians, African Americans, and Latinos.

The IL28B gene encodes interferon lambda, which is involved in viral resistance and is up-regulated by interferons. IL28B polymorphisms are strong independent predictors of  responsiveness to combination therapy with pegylated interferon and ribavirin in patients with HCV genotype 1. Response is closely associated with a single-nucleotide polymorphism (SNP), designated rs12979860, located 3 kilobases upstream from the interleukin 28B gene locus (IL28B) on human chromosome 19.

Patients with the CC genotype at the rs12979860 polymorphic site have 2 to 3 fold higher SVR  than patients with the CT or TT genotypes. The CC genotype has also been associated with a 3-fold increase in rate of spontaneous clearance of HCV. 

Frequency of the rs12979860 C allele varies across different racial and ethnic groups. This polymorphism is most frequently present in individuals from East Asia and least common in individuals of African origin. In a recent US-based study, the CC genotype was observed in 37% of Caucasians, 29% Hispanics, and 14% of African Americans tested.

The impact of the IL28B-related polymorphism on response rates in patients infected with HCV genotypes other than genotype 1 is still being investigated. 

Specimen requirement is 3 mL of whole blood collected into a lavender top tube containing EDTA as anticoagulant.

References

Stattermayer AF, Ferenci P, Effect of IL28B genotype on hepatitis B and C virus infection, Curr Opin Virol, 2015;14:50-55.

Sarrazin C et al, Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients, J Hepatol,2011;54(3):415-421.