IL28B in the Era of Direct-acting Antivirals for Hepatitis C

Abstract

The IL28B genotype is the strongest baseline predictor of hepatitis C treatment response with peginterferon-α and ribavirin. In 2011, 2 protease inhibitors were approved for genotype 1 infection in combination with peginterferon-α and ribavirin, and boceprevir and telaprevir attenuate the association between the IL28B genotype and treatment response. Although sustained virologic response rates are improved for all IL28B genotypes with the addition of the protease inhibitors, the unfavorable IL28B genotypes have substantial benefit. IL28B also predicts the likelihood of shortened duration of treatment with the protease inhibitor combination. As hepatitis C treatment moves towards interferon-free regimens, the role of IL28B in these regimens is under investigation.

Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes

“…However, there are several clinical as well as scientific reasons to pursue a deeper understanding of how IFNL genotype impact viral clearance. Several recent studies show that rs368234815 influences the response kinetics to DAA 28,30 ; however, the role of rs117648444 in DAA treatment has not yet been investigated. This suggests that patients not expressing IFNl4 can receive a shortened DAA treatment and possibly also reduced doses.…”

“…One may argue that the use of genetic markers may become obsolete with the advent of direct-acting antiviral agents (DAAs), due to their high cure rates [26][27][28] . Nevertheless, the role of IFNL3/ IFNL4 polymorphisms has been convincingly demonstrated in the first generation DAA treatment regimes.…”

Guarding the frontiers: the biology of type III interferons

“…The effect of IFNL4 genotype is not restricted to IFN-based therapies for HCV; it also extends to direct-acting antiviral-based treatments [95][96][97][98][99] . Furthermore, IFNL4 genotype also influences the reactivation of cytomegalovirus (CMV) in immune-suppressed patients 100,101 .…”

Impact of host and virus genome variability on HCV replication and response to interferon

“…However, with the addition of boceprevir the rates of SVR increased significantly in patients with the unfavorable genotypes (59% for CT and 71% for TT, compared to 27% and 28% respectfully). The findings with triple therapy using telaprevir were generally similar to that of boceprevir [73]. Patients with the favorable CC genotype had an increased chance of SVR to 90% while the response of the unfavorable genotypes was approximately 70% (due to the nature of this retrospective analysis, no formal statistics were performed).…”