IL-28B Polymorphisms and the Response to Antiviral Therapy in HCV Genotype 2 and 3 Varies by Ethnicity

A Meta-Analysis

A. S. Rangnekar; R. J. Fontana

Disclosures

J Viral Hepat. 2013;20(6):377-384. 

In This Article

Discussion

While IL-28B genotyping has an important role in HCV genotype 1 patients treated with pegIFN and ribavirin, its value in HCV patients with genotype 2/3 remains less clear.[2] This meta-analysis demonstrates that the favourable IL-28B genotype is a significant predictor of SVR in Caucasian patients with HCV genotype 2/3 treated with pegIFN and ribavirin for 24 weeks. Additionally, IL-28B genotype may be predictive of SVR in Asian patients with HCV genotype 2, although the pooled OR of SVR did not reach statistical significance perhaps due to inadequate sample size (Fig. 2).

Figure 2.

Forest plots of IL-28B genotype and SVR in patients with hepatitis C virus (HCV) genotype 2/3 infection stratified by race. (A) There were 11 studies of 1599 Caucasian HCV genotype 2/3 patientsm and (B) there were five studies of 833 Asian HCV genotype 2 patients. SVR, sustained virologic response.

Our results also suggest that the favourable IL-28B genotype increases the odds of achieving RVR in Caucasian and Asian patients with HCV genotype 2/3 infection, a finding similar to that reported in HCV genotype 1 patients.[2] Furthermore, the results of this study demonstrate that IL-28B genotype may be helpful in stratifying the odds of SVR in patients with HCV genotype 2/3 who do not achieve RVR. Prior data suggest that HCV genotype 2/3 patients with low viral load who achieve RVR may be candidates for a shortened duration of therapy to 12–16 weeks.[25,26] However, it is unclear whether the favourable IL-28B genotype can be used to further identify patients from this group who are more likely to achieve SVR and/or are at lower risk of relapse. Individual studies have not found an association between IL-28B genotype and SVR rates in patients treated for <24 weeks after achieving RVR, but they may be under-powered.[13,19] Therefore, IL-28B testing may play an important role in counselling individual patients that are receiving antiviral therapy and particularly in those experiencing side effects who do not achieve RVR.

In the era of DAAs, IL-28B testing in HCV genotype 1 patients may be limited to specific populations in which DAAs are not yet approved, such as in those with HIV co-infection.[2] In contrast, pegIFN and ribavirin are the only currently approved agents for HCV genotype 2/3 infection. An improved ability to predict SVR may be particularly important for patients intolerant to this regimen, but the absolute difference in response rates in those with and without the favourable IL28-B genotype is small.

In contrast to our results, another recent meta-analysis of IL-28B testing and SVR in patients of combined HCV genotypes reports a statistically significant pooled OR of SVR in Asians with HCV genotype 2 infection,[5] a finding likely due to the inclusion of only two Asian studies. Our own subgroup analysis of five Asian studies identified a strong trend which does not reach statistical significance. The meta-analysis by Chen et al. also demonstrates a lack of association between the favourable IL-28B genotype and SVR in Caucasian patients with HCV genotype 2/3, although only five studies were included. Assessing the role of IL-28B testing in nonCaucasian patients with HCV genotype 2/3 was limited in our study. Among the five pooled Asian studies, two explicitly included some treatment-experienced patients who may have reduced the impact of IL-28B genotyping in predicting SVR. In addition, there were no studies of HCV genotype 2/3 African American patients, a group with traditionally lower response to interferon. However, a substantially lower proportion of African Americans are infected with HCV genotype 2/3 in the general US population compared to Caucasians (i.e. 5% vs 20–30%).[27,28] Because of the lack of stratification by HCV genotype in many studies, we were unable to determine whether IL-28B genotype has greater utility in patients with HCV genotype 2 vs 3. However, this issue is worthy of further study because HCV genotype 3 patients with a high baseline HCV RNA level are more prone to relapse after a 24-week course of treatment compared to those with HCV genotype 3 and low viral load or HCV genotype 2 infection.[29] Finally, how IL-28B testing fits in with other known pretreatment predictors of SVR remains unknown.

In conclusion, this meta-analysis demonstrates that the favourable IL-28B genotype is significantly associated with SVR in Caucasian patients with HCV genotype 2/3 infection treated with pegIFN and ribavirin for 24 weeks. However, the magnitude of the absolute difference in SVR rates (83% vs 78%) is small and may not influence the decision to initiate treatment. In addition, the favourable IL-28B genotype is associated with RVR as well as SVR in patients who do not achieve RVR, and this information may prove useful to clinicians when counselling individual patients during therapy.

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