47th Annual Gastroenterology Update: IL-28B Predictor of Response to Hepatitis C Therapy


"IL-28B receptor polymorphism is an important predictor of SVR in patients treated with pegylated interferon and ribavirin," said Binu John, MD at the Cleveland Clinic.

Cleveland, OH—Prior to 2009, the relationship between interleukin-28B (IL-28B) and hepatitis C was in its infancy, said Binu John, MD, MPH at the Cleveland Clinic, offering his perspective on the rapid pace of research on genetic predictors of response to hepatitis C therapy performed in recent years. During his presentation, Dr. John summarized the recent developments on IL-28B receptor polymorphism as a predictive marker for response to hepatitis C treatment.

"Host and viral predictors of a poor response to therapy in patients with hepatitis C include genotype 1, high serum hepatitic C virus (HCV) RNA levels (viral load greater than 600,000), advanced liver fibrosis, increased age, co-infection with HIV, high body mass index, and race and genetic factors,” said John, setting the stage to describe the role of IL-28B polymorphism in hepatitis C treatment.

Multiple studies have demonstrated that African Americans have significantly lower sustained viral response (SVR) to hepatitis C therapy when compared to Caucasians, noted John. However, it was unclear the role ethnicity played in this treatment disparity.

“We knew that genetics plays a role in determining whether some patients with hepatitis C do not respond to treatment, but we did not understand the biologic mechanism,” said John. Recent advances in genome-wide association studies enabled researches to identify single nucleotide polymorphisms in close proximity to the gene.

John presented data published by Ge and colleagues that found patients with the C/C genotype of the rs12979860 single nucleotide polymorphism (SNP), which is located 3 kilobases upstream of the IL-28B gene, had a 5- to 7-fold higher response to treatment with pegylated interferon and ribavirin compared to patients with either the C/T or T/T polymorphism. And the authors found this relationship was consistent across different ethnicities, he said. The study showed the most significant factor that predicted SVR was the favorable C/C genotype.

John noted several subsequent studies investigating both the rs12979860 SNP and rs8099917 SNP, which is located 8.9 kb downstream from IL-28B, have confirmed these findings.

“IL-28B receptor polymorphism is an important predictor of SVR in patients treated with pegylated interferon and ribavirin,” concluded John.

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