Interleukin-28B (IL28B) has been a phenomenal discovery in the field of hepatitis C (HCV); yet, with the emergence of direct-acting antiviral (DAA) agents, its importance has been overshadowed. While the long-term significance of IL28B is unclear, for now, it has significant clinical utility. Three reviews/commentaries help elucidate its role:
▪ Hepatology 2012; 56: 361-66. IL 28B Genetics and Biology
▪ Hepatology 2012; 56: 367-372 Clinical Utility of IL28B
▪ Hepatology 2012; 56: 373-380 Relevance of IL28B in age of DAAs
Key points from these references:
African-Americans are less likely to respond to treatment with pegylated interferon (PEGIFN) (and ribavirin [RBV]) in large part due to a low frequency of favorable alleles (C/C genotype) to IL28B.
Predictors of response to treatment with PEGIFN/RBV:
▪ CC IL28B genotype: OR 5.9 (compared to non-CC genotype)
▪ HCV RNA level ≤600,000 IU/mL: OR 3.1 (compared to >600,000 IU/mL)
▪ Degree of fibrosis, metavir F0-2: OR 2.7 (compared with F3-F4)
▪ Rapid virological response: OR 9.1 (compared with non-RVR non CC genotype)
Overall CC genotype is associated with double the sustained virological response (SVR).
Vitamin D also plays an important role in innate immunity and deficiency is associated with lower SVR.
Algorithm for use of IL28B (applicable to patients ≥18 years):
▪ Consider obtaining IL28B in all genotype 1 patients:
▪ If CC genotype and does not have risk factors for poor response (including cirrhosis, high viral load), then likely to treat with PEGIFN/RBV and monitor for RVR. In patients without RVR, addition of DAA would be reasonable.
▪ If risk factors for poor response or if non-CC genotype (C/T or T/T), then consider use of DAA at onset of therapy
DAAs are expensive. Boceprevir (BOC) costs $26,000 for 24 weeks & $48,000 for 44 weeks. Telaprevir (TVR) costs $49,000 for 12 weeks. These costs are in addition to costs for PEGIFN/RBV which is approximately $30,000. The cost of testing IL28B status is approximately $300.
In patients with CC IL28B genotype, the main advantage of DAAs may be to shorten treatment course by increasing the likelihood of RVR; though with TVR, the SVR was improved even among CC genotype patients in the “ADVANCE” trial (90% compared with 64%). In non-CC IL28B genotype, TVR or BOC is associated with > 2-fold increase in SVR. The specific response rates for both TVR and BOC are available in these references.
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