IL28B and antiviral therapy of chronic viral hepatitis: what remains?

Treating patients with chronic viral hepatitis constitutes a complex and demanding clinical task due to the long-term therapy, which is associated with limited efficacy, high costs and possible various side effects. Recently, genome-wide association studies identified genetic polymorphisms within the IFNL3 gene region (IL28B) as a major treatment predictor in chronic hepatitis C virus (HCV) infection. However, the underlying molecular mechanisms remain largely unknown. In chronic HCV infection IL28B polymorphisms are associated both with spontaneous and treatment-induced clearance of the virus as well as with surrogate markers of the infection (e.g. viral genotype, baseline viral load, inflammation and hepatic steatosis). A correlation of the IL28B genotype with treatment outcome is shown in decreasing significance by dual interferon/ribavirin treatment, triple therapy with protease inhibitors and interfer-on-free regimens. Tailoring therapy duration and intensity based on IL28B polymorphisms is currently under investigation in several clinical studies. In contrast, studies on the association of IL28B polymorphisms with treatment response in chronic hepatitis B infection have so far yielded contradictory results.