Abstract
Background. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphism is associated with high rates of sustained virological response (SVR) to peginterferon (PegIFN) and ribavirin (Rbv) in hepatitis C virus genotype-1 (HCV-1) patients. The impact of baseline predictors of treatment outcome and their interplay with viral kinetics in HCV-1 CC patients has not been fully evaluated. Aim. To identify baseline and on-therapy predictors of treatment failure in HCV-1 IL28B CC patients. Methods. Treatment-naïve HCV-1 patients, compliant to PegIFN and Rbv who did not discontinue treatment for nonvirological reasons, were analyzed. Results. 109 HCV-1 IL28B CC were studied. Sixty were males, 39 with BMI >25, 69 with >600,000 IU/mL HCV RNA, 15 with HCV1a, and 30 with cirrhosis. Overall, 75 (69%) achieved an SVR; cirrhosis was the only baseline predictor of treatment failure (OR: 2.58, 95% CI: 1.07–6.21) as SVR rates were 53% in cirrhotics versus 75% in noncirrhotics (P = 0.03). HCV RNA undetectability (<50 IU/mL) at week 4 (RVR) was achieved by 58 patients (53%). The SVR rates were independent of RVR in noncirrhotics, 76% (34/45) RVR (+) and 74% (25/34) RVR (−) (P = 0.9). In cirrhotic patients, SVR rates were significantly higher in RVR (+) compared to RVR (−) (10/13 (77%) versus 6/17 (35%) P = 0.03). Conclusions. In HCV-1 IL28B CC patients, cirrhosis is the only clinical baseline predictor of PegIFN and Rbv treatment failure. However, in IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy.
Highlights
Chronic infection with hepatitis C virus (HCV) affects almost 200 million people worldwide, representing a leading cause of cirrhosis and anticipated liver-related death [1]
The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphism is associated with high rates of sustained virological response (SVR) to peginterferon (PegIFN) and ribavirin (Rbv) in hepatitis C virus genotype-1 (HCV-1) patients
Such IL28B guided recommendations do not confer any clinical meaningfulness to other baseline moderators of treatment failure in IL28B CC patients nor do they value on-treatment viral kinetics in these patients. This is extremely significant as HCV RNA kinetics during treatment have been repeatedly shown to possess a stronger predictive power in terms of treatment outcome than any baseline pretreatment factor. With this as a background, we investigated HCV-1 IL28B CC patients treated with PegIFN plus Rbv to identify baseline and ontreatment predictors of treatment outcome
Summary
Chronic infection with hepatitis C virus (HCV) affects almost 200 million people worldwide, representing a leading cause of cirrhosis and anticipated liver-related death [1]. The high SVR rates obtained with PegIFN/Rbv in patients with the favorable IL28B genotype (CC) question the need for DAAs including regimens in these patients Further supporting such an assumption is a recent Markov model costeffectiveness analysis demonstrating that a DAA-based regimen does not provide added benefits over PegIFN/Rbv in this subgroup of patients [11]. The only exemption being IL28B CC patients with cirrhosis, where a DAA-based regimen is considered the SOC by most guidelines due to a somewhat reduced efficacy of PegIFN and Rbv in these patients Such IL28B guided recommendations do not confer any clinical meaningfulness to other baseline moderators of treatment failure in IL28B CC patients nor do they value on-treatment viral kinetics in these patients. In IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy
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