Epidemiology

IL28B gene variations predict response to hepatitis C treatment

Last Updated: 2010-09-13 17:12:08 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - In patients with HIV and hepatitis C virus (HCV) coinfection, variations in the IL28B gene predict response to pegylated interferon plus ribavirin, researchers from Spain report .

Current treatment algorithms, which are based on HCV genotype and viral load, don't predict treatment response very precisely, coauthor Dr. Karin Neukam told Reuters Health by e-mail.

In her team's opinion, she said, the polymorphism "reported in our study should be included in algorithms for HCV treatment and routine testing of the genotype should be part of future treatment strategies," especially in HIV/HCV coinfected patients, in whom success rates are lower.

As they reported online August 30th in Clinical Infectious Diseases, Dr. Neukam from Hospital Universitario de Valme, Seville, and colleagues assessed whether the single-nucleotide polymorphism rs12929860 in the IL28B region independently predicts a sustained virological response (SVR). Their subjects were 154 HIV-infected patients with chronic HCV who were treated with pegylated interferon plus ribavirin without HCV genotype restriction.

Seventy-seven patients (46%) attained an SVR, including 33 of 111 (30%) with HCV types 1-4 and 44 of 58 (76%) with HCV types 2-3.

The rates of SVR were significantly higher among patients with the CC genotype (71%) than among those with TT (50%) or TC (29%) genotypes.

In contrast, significantly fewer nonresponders were CC carriers (9, or 18%) than TT/TC (41, or 82%).

The differences in SVR rates between patients with different genotypes was most pronounced among those with HCV type 1 or 4 (54% in CC carriers vs. 19% in TT/TC carriers; p<0.001). SVR rates were not significantly different for those with HCV types 2 or 3 (93% in CC carriers vs. 77% for TC/TT carriers).

Median low density lipoprotein cholesterol levels were also higher in CC vs. TT/TC carriers (89 vs. 75 mg/dL), leading researchers to speculate "that an rs12979860 genotype other than CC could induce soluble isoforms of the LDL receptor, which join to plasma LDL, decreasing LDL levels and allowing an easier entrance of HCV into the hepatic cell."

In multivariate analysis, independent predictors of SVR included HCV genotype 2-3, genotype CC, plasma HCV RNA level of 600,000 IU/mL or lower, and female sex.

Summing up, Dr. Neukam said, "Our results show that the IL28B genotype is an important independent predictor of treatment response and should therefore be considered in the treatment decision, as anti-HCV treatment becomes more and more individualized."

SOURCE: http://link.reuters.com/den33p

Clin Infect Dis 2010;51:788-795.