Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8406
Peer-review started: June 28, 2016
First decision: July 29, 2016
Revised: August 9, 2016
Accepted: August 23, 2016
Article in press: August 23, 2016
Published online: October 7, 2016
To determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients.
One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems).
Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P < 0.001), urban residence (P = 0.004), IL28B CC genotype (P < 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P < 0.001) and early virological response (P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P < 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%.
HCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.
Core tip: The high cost of the newly introduced direct acting antivirals precludes universal replacement of the suboptimal interferon-based therapy for chronic hepatitis C. Therefore, a series of host- and virus-related factors are used as prognostic markers of treatment response. In Asian patients, a newly described viral factor is represented by amino acid substitutions in the hepatitis C virus core protein at positions 70 and 91. The present study confirms that core substitutions are also found in Caucasian patients and, together with age and IL28B genotype, can be used as predictors of the outcome of interferon-based therapy.