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

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.