Genetic variation in interleukin-28B locus is associated with spontaneous clearance of HCV in children with non-1 viral genotype infection

Abstract

In this report from France, undetectable serum hepatitis C virus (HCV) RNA at 12 weeks (Wþ12) (409 patients) post-treatment follow-up was as relevant as undetectable serum HCV RNA at 24 weeks (Wþ24) (sustained virological response [SVR]; 408 patients) after the end of treatment.Current standard therapy is based on a combination of pegylated interferon (PEG-IFN) and ribavirin, but it leads to only $50% SVR in patients with HCV genotype 1 and high viral loads.2 IFN reduced the risk for HCC, especially among patients with SVR.3,4 Then, we need to accurately judge whether the patient is SVR or non-SVR, applying the present standard for the judgment of SVR with the undetectability of serum HCV RNA at post-treatment Wþ24.We investigated 102 patients with chronic hepatitis C genotype 1 treated with PEG-IFN-alfa 2a plus ribavirin for 48 weeks. Some of these patients had already been included in previous reports. 5,6 Serum HCV RNA was measured using the COBAS TaqMan HCV test with a detection limit of 1.2 logIU/mL. At the Wþ24 posttreatment follow-up, 40 (39.2%) patients had SVR, and 31 (48.4%) and 9 (23.6%) were treatment naïve and previously treated patients, respectively. At Wþ12, serum HCV RNA was undetectable in 42 patients, and 40 patients were SVR (PPV, 95.2%). We found two relapsers at Wþ24 (undetectable at Wþ12).In the case of using direct-acting antivirals, earlier knowledge of treatment outcome would be useful for retreatment for the same patient. Taken together, our findings show that Wþ12 undetectable serum HCV RNA is not suitable for predicting persistent virological response. Further understanding of the mechanism of relapse could be useful in reducing the posttreatment follow-up period from the current standard of 24 weeks. Reply:We read, with interest, the letter by Kanda et al. regarding our article. As you know, the primary end-point of antiviral therapy for chronic hepatitis C virus (HCV) is achieving sustained virological response (SVR), defined as undetectable HCV-RNA in serum 24 weeks after stopping antiviral therapy. SVR is equivalent to viral eradication and is associated with a reduction in the risk of cirrhosis and hepatocellular carcinoma.1 Recently, it has been proposed that a 12-week post-treatment follow-up might be as relevant as 24 weeks to determine the SVR in patients with HCV receiving pegylated-interferon (PEG-IFN) and ribavirin.2 In our study, 573 patients who received combination PEG-IFN and ribavirin and had a virological response at the end of treatment were evaluated. Serum HCV-RNA was measured, using a new assay based on transcription-mediated amplification (TMA), with a lowest detection limit of 5-10 IU/mL, at week (W)þ12 and Wþ24 after the end of treatment. At the Wþ24 post-treatment follow-up, 408 (71%) patients had an SVR, 181 (71.2%) were treated with PEG-IFN alpha-2a and ribavirin, and 227 (71.1%) were treated with PEG-IFN alpha-2b and ribavirin. At Wþ12, serum HCV-RNA was undetectable in 409 patients, and 408 patients were SVR (positive predictive value [PPV]: 99.7%; 9...

Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data

“…The present results confirm the association demonstrated in adults [1]. Two preliminary paediatric studies were already published on the same topic [7], [8] that enrolled a limited number of patients (n = 15 and n = 26, respectively) and used the classical approach of comparing the frequencies of the C/C genotypes in children with clearance and chronic infection. In the present study a significantly higher number of children was enrolled and the value of the results was enforced and validated by the comparisons of alleles and genotypes frequencies among children with chronic infection, spontaneous clearance and, differently by previous studies, with a cohort of ethnically matched controls.…”

“…Only two studies on small cohorts of children are available so far on the topic [7], [8]. The natural history of hepatitis C in children is different when compared to adults [9], [10].…”

No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients

“…Recent studies have suggested that the SNPs rs12979860, rs8099917, rs12980275, and rs8103142 are correlated with treatment outcome and spontaneous viral clearance 11,12,16,17,18,19,20. The most frequently observed variants, rs12979860 CC and rs8099917 TT, are significantly associated with SVRs to PEG-IFN plus RBV therapy among HCV genotype 1 patients 11,12.…”

Perinatal transmission of hepatitis C virus: an update

“…With regard to single nucleotide polymorphisms of interleukin (IL)-28B that have been demonstrated to be important in determining spontaneous and treatment-induced clearance of HCV in children and in adults [96][97][98] recently, neither the mother's nor the children's IL-28B status was associated with an increased risk of perinatal transmission [98].…”