IL28B gene of chromosome 19 as a predictor of SVR in HCV antiviral therapy...

From the Irish Medical Times - we've seen before many times the correlation between SVR and variations in the interleukin 28B (IL28B) gene of chromosome 19, but this serves as a reminder of how powerful a predictor it can be. LabCorp offers a commercial assay available to HCV providers here in the States


Genetic markers promising as guide to HCV therapy
September 9, 2011 By Mary Anne Kenny

Two genes first described in 2009 and 2010 have considerable promise as predictors of patients’ responses to pegylated interferon and ribavirin, Australian hepatologists have claimed.

Dr Jacinta Holmes and colleagues from St Vincent’s Hospital in Melbourne said variations in the interleukin 28B (IL28B) gene of chromosome 19 were known to be strongly associated with treatment outcome in patients with hepatitis C virus genotype 1 (HCV-1) receiving the two medications.

“Patients carrying the ‘good response’ variant had two- to three-fold higher rates of sustained virological response (SVR),” they said.

Differences in the frequency of the alleles in different racial groups also explained much of the known racial disparity in response rates.

IL28B polymorphism had also been associated with spontaneous clearance of acute HCV infection.

Two functional variants of the second gene, located on chromosome 20 and coding for inosine triphosphatase, had been found to protect against ribavirin-induced haemolytic anaemia. This side effect was dose-limiting in up to 15 per cent of patients enrolled in clinical trials.

“These exciting genetic discoveries are changing how we think about HCV pathogenesis, patient evaluation and current treatment paradigms,” they said. More research was needed, however, before the tests were likely to be incorporated into routine practice.

Although pegylated interferon and ribavirin were the current standard of care for HCV, the success rate was disappointing, as only about 55 per cent of patients achieved an SVR. In these circumstances the cost and side effects of treatment were an important consideration, the authors said.

“It would be clinically useful to be able to accurately predict at baseline which patients are most likely to achieve SVR, both to prioritise their treatment and spare unnecessary morbidity for those with a very low probability of clearance,” they concluded.

Clinical Liver Disease
2011; 15: 497-513.