Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection

Joshita, Satoru; Umemura, Takeji; Katsuyama, Yoshihiko; Ichikawa, Yūki; Kimura, Takefumi; Morita, S.; Komatsu, Michiharu; Ichijo, Tetsuya; Matsumoto, Akihiro; Yoshizawa, Kaname; Kamijo, N.; Ôta, Masao; Tanaka, Eiji

doi:10.1016/j.humimm.2011.12.021

Cited by 37 publications

(30 citation statements)

References 15 publications

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“…A similar finding was reported that the C-allele has a protective role in the development of HCV-induced HCC and in HCV recurrence after liver transplantation [27]. On the contrary, other studies have reported that the variants of IL28B may not be involved in the hepatocarcinogenesis of HCV-infected patients [25, 28]. Results reported in the present study were in agreement with that of the latter studies as none of the five IL28B genetic variants investigated in this study had any significant effect on the advancement of HCV infection to cirrhosis and/or HCC; though, we did observe that these SNPs could have a significant role in the establishment of HCV infection as they showed significant differences in distribution between patients and healthy control subjects.…”

Section: Discussionsupporting

confidence: 74%

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Al‐Qahtani

Al-Anazi

Abdo

et al. 2015

Journal of Immunology Research

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Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P = 0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P = 0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae.

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Section: Discussionsupporting

confidence: 74%

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Al‐Qahtani

Al-Anazi

Abdo

et al. 2015

Journal of Immunology Research

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“…In the context of HCC, two studies associated IFN-λ3 rs12979860 unfavorable CT or TT alleles with liver cirrhosis and the development of HCC in patients chronically infected with HCV (100, 101). However, this was not confirmed in two other independent studies in Japanese (102) or Italian cohorts (97). Finally, HCV-related liver disease is a multifactorial problem, and the independent association of genetic factors may not be a clear cut.…”

Section: Ifn-λ During Treatment With Direct-acting Antivirals (Daa) Amentioning

confidence: 69%

Type III Interferons in Hepatitis C Virus Infection

Boisvert

Shoukry

2016

Front. Immunol.

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The interferon (IFN)-λ family of type III cytokines includes the closely related interleukin (IL)-28A (IFN-λ2), IL-28B (IFN-λ3), and IL-29 (IFN-λ1). They signal through the Janus kinases (JAK)-signal transducers and activators of transcription pathway and promote an antiviral state by the induction of expression of several interferon-stimulated genes (ISGs). Contrary to type I IFNs, the effect of IFN-λ cytokines is largely limited to epithelial cells due to the restricted pattern of expression of their specific receptor. Several genome-wide association studies have established a strong correlation between polymorphism in the region of IL-28B gene (encoding for IFN-λ3) and both spontaneous and therapeutic IFN-mediated clearance of hepatitis C virus (HCV) infection, but the mechanism(s) underlying this enhanced viral clearance are not fully understood. IFN-λ3 directly inhibits HCV replication, and in vitro studies suggest that polymorphism in the IFN-λ3 and its recently identified overlapping IFN-λ4 govern the pattern of ISGs induced upon HCV infection of hepatocytes. IFN-λ can also be produced by dendritic cells, and apart from its antiviral action on hepatocytes, it can regulate the inflammatory response of monocytes/macrophages, thus acting at the interface between innate and adaptive immunity. Here, we review the current state of knowledge about the role of IFN-λ cytokines in mediating and regulating the immune response during acute and chronic HCV infections.

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“…A large-scale European genome-wide association study (GWAS) recently identified a weak protective role for the rs12979860 T allele in the progression of fibrosis during HCV infection (37), whereas a Japanese GWAS identifying a susceptibility locus for HCV-induced HCC found no association of rs12979860 and rs8099917 SNPs with HCC (38). In support of these findings, Joshita and colleagues reported no association between the IL-28B genotype and the incidence of primary HCC (39). These results show a good concordance with those of the present study, which revealed that the IL-28B genotype was not associated with HCC incidence before treatment (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Association of Interleukin-28B Genotype and Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C

Hodo

Honda

Tanaka

et al. 2013

Clinical Cancer Research

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Purpose: Several single-nucleotide polymorphisms (SNP) in the interleukin-28B (IL-28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CHC). However, such an association with hepatocellular carcinoma (HCC) is unkno3 we investigated the association between the IL-28B genotype and the biology and clinical outcome of patients with HCC receiving curative treatment.Experimental Design: Genotyping of 183 patients with HCC with CHC who were treated with hepatic resection or radiofrequency ablation (RFA) was carried out, and the results were analyzed to determine the association between the IL-28B genotype (rs8099917) and clinical outcome. Gene expression profiles of 20 patients with HCC and another series of 91 patients with CHC were analyzed using microarray analysis and gene set enrichment analysis. Histologic and immunohistochemical analyses were also conducted.Results: The TT, TG, and GG proportions of the rs8099917 genotype were 67.8% (124 of 183), 30.6% (56 of 183), and 1.6% (3 of 183), respectively. Multivariate Cox proportional hazard analysis showed that the IL-28B TT genotype was significantly associated with HCC recurrence (P ¼ 0.007; HR, 2.674; 95% confidence interval, 1.16-2.63). Microarray analysis showed high expression levels of IFN-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL-28B TG/GG genotype. Histologic findings showed that more lymphocytes infiltrated into tumor tissues in the TG/GG genotype.Conclusions: The IL-28B genotype is associated with HCC recurrence, gene expression, and histologic findings in patients with CHC.

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Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection

Cited by 37 publications

References 15 publications

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Correlation between Genetic Variations and Serum Level of Interleukin 28B with Virus Genotypes and Disease Progression in Chronic Hepatitis C Virus Infection

Type III Interferons in Hepatitis C Virus Infection

Association of Interleukin-28B Genotype and Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C

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