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

Results

An initial search revealed 308 studies of IL-28B among which 88 specifically evaluated virologic outcomes in treated patients An additional 63 studies were excluded due to the inclusion of previously treated patients, acute HCV infection, use of alternative IL-28B SNPs, use of DAAs, inclusion of liver transplant recipients, combined ethnicities or nongenotype 2/3 patients. Of the remaining 25 studies, nine were excluded due to redundant study populations, HIV co-infection or use of alternative treatment regimens, leaving 16 studies in the current analysis (Fig. 1).

Figure 1.

Study selection overview. From a total of 308 studies, 16 studies met the inclusion criteria.

Caucasians With HCV Genotype 2/3

SVR Outcome. There were 11 studies of Caucasians with HCV genotype 2/3.[3,10–19] Among 1599 patients, 43% had the favourable IL-28B genotype CC at rs12979860 (Table 1). Overall, 83% of patients with the favourable IL-28B genotype achieved SVR as compared to 78% of patients with the unfavourable genotype, with a pooled OR of 1.36 (95%CI: 0.98–1.88, P = 0.07) with low heterogeneity between studies (I 2 = 29%). In a subgroup analysis of eight studies that included only treatment naïve patients, the pooled OR of SVR was 1.21 (95%CI: 0.85–1.74, P = 0.29). Among the eight studies with pegIFN and ribavirin treatment for at least 24 weeks, the pooled OR of SVR was 1.55 (95%CI: 1.10–2.18, P = 0.01) as compared to 1.17 (95%CI: 0.53–2.58, P = 0.70) in the studies with variable duration treatment regimens. Among the four studies that used a ribavirin dose ≥800 mg/day for at least 24 weeks, the pooled OR of SVR was 1.02 (95%CI: 0.55–1.92, P = 0.95). The pooled OR was 1.49 (95%CI: 1.02–2.19, P = 0.04) in the six high-quality studies vs 1.33 (95%CI: 0.72–2.43, P = 0.36) in the five low-quality studies (Table 2).

RVR Outcome. Six studies reported RVR data in 1265 Caucasian patients of which 42% had the favourable IL-28B genotype. Seventy-seven percent of patients with the favourable IL-28B achieved RVR as compared to 65% of patients with the unfavourable genotype, with a pooled OR of 1.82 (95%CI: 1.12–2.96, P = 0.02) and moderate heterogeneity between studies (I 2 = 69%).

Among 350 patients who achieved RVR in three studies, 89% of 142 patients with the favourable IL-28B genotype and 85% of 208 patients with the unfavourable IL-28B genotype also achieved SVR (pooled OR: 1.37, 95%CI: 0.71–2.67, P = 0.35). In contrast, among 184 patients who did not achieve RVR, 78% of 68 patients with the favourable IL-28B and 50% of the 116 with the unfavourable IL-28B genotype achieved SVR (pooled OR: 3.29, 95%CI: 1.67–6.51, P = 0.001).

Asians With HCV Genotype 2

SVR Outcome. There were five studies[20–24] of 833 Asian patients with HCV genotype 2 infection, in which 86% had the favourable IL-28B genotype. Overall, 86% of patients with the favourable IL-28B genotype achieved SVR, while 75% of patients with the unfavourable IL-28B genotype achieved SVR with a pooled OR of 1.99 (95%CI: 0.94–4.25, P = 0.07). There was low to moderate heterogeneity between studies (I 2 = 44%). In a subgroup analysis of the two studies that explicitly included only treatment naïve patients, the pooled OR of SVR was 1.54 (95%CI: 0.81–2.93, P = 0.18). Among the four low-quality studies, the pooled OR was 2.22 (95%CI: 01.14–4.35, P = 0.02).

RVR Outcome. In the two studies reporting RVR data, 88% of the 594 patients had the favourable IL-28B genotype. Eighty-two percent of patients with the favourable IL-28B genotype and 62% of patients with the unfavourable genotype achieved RVR, with a pooled OR of RVR of 2.39 (95%CI: 1.39–4.11, P = 0.002).

Pooled Analysis

After combining the 16 studies with 2432 patients, the pooled OR of SVR in patients with the favourable IL-28B genotype was 1.48 (95%CI: 1.09–2.02, P = 0.01). There was low heterogeneity between studies (I 2 = 34%). The pooled OR was 1.27 (95%CI: 0.95–1.69, P = 0.11) in the 10 studies with only treatment naïve patients and 1.44 (95%CI: 0.98–2.11, P = 0.06) among the seven high-quality studies. There was no evidence of publication bias by the Harbord or Peters tests (P = 0.69 and P = 0.33, respectively).

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