Interleukin 28B Polymorphisms Research Articles

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients.

In various genome-wide correlation studies, interleukin (IL)28B gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of IL28B (rs12979860) in patients with chronic hepatitis C and assess the IL28B polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of IL-28B (rs12979860) was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (p < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore IL-28B (rs12979860) SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.

Association of Interleukin-28B Polymorphisms (rs12979860 C/T, rs12980275 A/G, rs8099917 T/G) and Risk of Hepatocellular Carcinoma in an Iranian Population.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The association of interleukin 28B (IL-28B) polymorphisms and HCC has been investigated in several populations. However, the findings are controversial. This study aimed to address the association between IL-28B polymorphisms (rs 8099917 T/G, rs12979860 C/T, rs12980275 A/G) and the risk of HCC in an Iranian population. METHODS: We have evaluated the association between IL-28B polymorphisms (rs 8099917 T/G, rs12979860 C/T, rs12980275 A/G) and HCC in 180 Iranian individuals (60 patients with HCC and 120 healthy matched controls) using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Single nucleotide polymorphism (SNP) association analysis and also haplotypes were estimated using the SNPstats online software. RESULTS: There was no significant association between these three polymorphisms of IL-28B and HCC (P>0.05). Moreover, haplotype analysis showed no significant association between the haplotypes and HCC. CONCLUSION: There was no association between IL-28B polymorphisms and HCC in an Iranian population.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Possible relationship between IL28B rs12979860 and TLR2 -196 to -174 del/ins polymorphisms and the liver fibrosis stage in hepatitis C patients.

It has been shown that host factors play an important role in the progression of hepatitis C virus (HCV) infection. Toll-like receptor 2 (TLR2) del and interleukin 28B (IL28B) T alleles can mediate liver inflammation and pathogenesis of hepatocellular carcinoma. In the present study, the possible relationship between the IL28B rs12979860 C/T and TLR2 -196 to -174 del/ins gene variants and different fibrosis stages and host factors in hepatitis C patients was investigated. IL28B and TLR2 polymorphisms in the blood of 50 hepatitis C patients at different stages of fibrosis (24 mild/moderate, 26 advanced) and 24 healthy controls were examined by RT-qPCR. The highest frequency of the TLR2 del (26.9%) and IL28B T (46.2%) alleles was found in hepatitis C patients with the most advanced fibrosis, and the lowest frequency was found in healthy controls. There was a statistically significant difference between hepatitis C patients with advanced fibrosis and healthy controls in terms of the TLR2 del (p = 0.0062) and IL28B T (p = 0.0017) allele frequencies. However, no statistically significant difference was found between the mild/moderate fibrosis and severe fibrosis patient groups in terms of genotype or IL28B and TLR2 polymorphisms (p > 0.05). In addition, there was a significant difference between patients with mild/moderate or advanced fibrosis who carried the TLR2 del allele together with the IL28B CT genotype and healthy controls. The present study emphasizes that the TLR2 and IL28B gene variants cannot be single biomarkers for the determination of fibrosis stage in hepatitis C infection but together can play an important role in predicting severe disease.

IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy

BackgroundImpact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. ResultsThree hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. ConclusionAbsolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Investigation of the Relationship Between IL28B Polymorphisms and Plasma IL28B Levels in Patients with Chronic Hepatitis B or C

Some single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) may increase susceptibility to infection and chronicity in humans with hepatitis B and C viruses. In our study, we aimed to investigate the prevalence of rs12979860, rs8099917 and rs12980275 SNPs in IL28B in patients with hepatitis B (HBV) or hepatitis C Virus (HCV) infection and to determine the relationship of these polymorphisms with plasma IL28B levels. For this purpose, 64 HBV-infected and 66 HCV-infected patients and 70 healthy individuals were included in the study. The SNPs were investigated by real time PCR (Polimerase Chain Reaction, Rt-PCR) using TaqMan SNP Genotyping Assay. The plasma levels of IL28B were detected by 'Enzyme Linked Immunosorbent Assay (ELISA)'. The frequencies of the rs12980275AG genotype and G allele (p= 0.003 and p= 0.04, respectively), and the rs12979860CT genotype and T allele (p= 0.01 and p= 0.04, respectively) were lower in HBV-infected patients. In HCV-infected patients, the rs8099917TG genotype and G allele frequencies (p= 0.04) were higher and the TGG haplotype showed a statistically significant difference (p= 0.04). The mean of IL28B plasma levels were higher in the control group than the HBV or HCV-infected patient groups (p= 0.001 and p= 0.01, respectively). However, HBV-infected patients with the rs12980275AG genotype showed a significant difference in plasma IL28B levels compared to the other genotypes (p= 0.0001) and these patients had lower viral loads (<105 IU/ml). According to the results of the study, it can be stated that rs12979860CT and rs12980275AG genotypes may play a role in preventing the chronicity of HBV infection, while rs8099917TG genotype may contribute to the transformation of HCV infection into chronic infection. In this study, it was observed that the presence of the G allele for the rs8099917 polymorphism could be evaluated as a risk allele for chronic HCV infection and that the TGG haplotype could have a strong predictive effect on increasing susceptibility to chronic HCV infection. It is recommended to evaluate the genotypic distribution of IL28B before treatment because of its prognostic significance in HBV or HCV infected patients. In HBV infection, the rs12980275AG genotype which is thought to have a protective effect by limiting viral replication with increased plasma IL28B levels, can be used as a good prognostic factor. These polymorphisms could be used as biomarkers to predict the clinical consequences of the patients infected with HBV or HCV, to take precautions to prevent the chronicity of the infection and its complications, and to develop new molecular targeted therapies with further research.

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients

Sofosbuvir has been approved as the first nonstructural protein 5Bpolymerase inhibitor with pan-genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first-in-class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV-4. Samples were collected at week zero. One hundred and thirty-one patients who reached the end of treatment (at week 12) were divided into three groups, according to their interleukin 28B genotype: Group A included 31 patients (CC genotype), group B included 79 patients (CT genotype) and group C had 21 patients (TT genotype). All patients received treatment for 3months in the form of sofosbuvir plus daclatasvir with ribavirin (in case of cirrhotic patients) or without ribavirin (in case of non-cirrhotic patients). Sustained virological response rate was significantly higher in patients with IL28B (CC genotype) vs. (non-CC genotype) (100 vs.88%) (p<0.0001).These patients also showed lower rates of post-treatment relapse and non-response, compared with the CT and TT patients (0% vs. (7.59% and 28.5%, respectively) (p<0.0001). Also, patients with CC genotype showed higher sustained virological response than non-CC genotypes on both cirrhotic (100% vs. 68.75%) and non-cirrhotic patients (100% vs. 91.66%) (p≤0.0001). Our results suggest that IL28B genotype contributes to the prediction of response to sofosbuvir plus daclatasvir.

Interferon-γ inducible protein-10 and interleukin 28B gene polymorphism as predictive markers for genotype 4 hepatitis C virus treatment response.

HCV genotype 4 dominates the HCV epidemic in Egypt. Drug resistance was the most serious side effect that reflects bad clinical outcome. Several studies had demonstrated that baseline serum interferon-γ-inducible-protein 10 (IP-10) levels and interleukin 28B polymorphisms were associated with the resistance to the standard of care pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy and development of post-treatment relapse. Our purpose was to assess the predictive value of combining IP-10 levels and IL28B genotypes to PEG-IFNα/RBV therapy response in Egyptian chronic HCV infection patients with genotype 4. Ninety Egyptian patients chronically infected by HCV genotype-4 treated with pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy were enrolled. Serum IP-10 levels were determined by enzyme linked immunosorbent assay pre- and post- treatment. IL-28B (rs12979860 and rs8099917) polymorphisms were performed by PCR-RFLP in all patients. Overall, 38 patients (42.2%) achieved sustained virologic response (SVR) and 52 (57.8%) patients have non-viral response (NVR). Pretreatment serum IP-10 mean levels were significantly lower in patients who achieved SVR than in NVR (P<0.05). CC genotype in IL28B polymorphism (rs12979860) was the favorable genotype as 65.8% achieved SVR, while TT genotype in IL-28B polymorphism (rs8099917) was the favorable genotype as 81.5% achieved SVR. Baseline IP-10 was significantly correlated to genotypes CC in rs12979860 and TT in rs8099917. Combined use of serum baseline IP-10 levels with IL-28B polymorphisms could improve the prediction of SVR to PEG-IFNα/RBV therapy in Egyptian chronic HCV infection patients with genotype 4.

Impact of Interleukin 28B and ICAM-1 Genetic Polymorphisms on Response to Direct Antiviral Treatment Among HCV Infected Patients.

Single nucleotide polymorphisms (SNPs) of IL-28B and/or ICAM-1 could have a role in expecting a response from HCV infected patients to direct antiviral agents (DAAs). The aim of the current study was to investigate the impact of IL-28B rs12979860 and rs8099917, and, ICAM-1 rs281437 SNPs on response to treatment with sofosbuvir + Daclatsvir ± Ribavirin, among HCV-infected Egyptian patients. Whole blood genomic DNA was extracted from 120 participants (80 HCV-infected patients and 40 healthy volunteers). HCV-infected patients were subdivided into responders and nonresponders to DAAs. Liver function testing, anti-HCV antibodies, HCV-RNA viral load and HCV genotyping were performed. IL-28B and ICAM-1 SNPs were evaluated by real-time PCR. ALT and AST levels were significantly higher among non-responder HCV infected patients (P = 0.001*). 90% of the patients had HCV genotype 4a and the remaining 10% had 4l genotype. Allelic discrimination revealed that IL-28B rs12979860 T, IL-28B rs809917 T and ICAM-1 rs281437 C alleles were more frequent among HCV-infected patients (responders or non-responders) than controls. However, IL-28B rs8099917 G allele was more frequent among healthy controls. Regarding the response to DAAs treatment, HCV-infected patients with IL-28B rs8099917 GG genotype showed a significantly earlier viral response compared to those carrying TT alleles. ICAM-1 rs281437 CT alleles were non significantly more frequent among responders. However, IL-28B rs12979860 alleles did not show any difference. Genotyping of IL-28B rs8099917 is a useful independent tool for expecting a response of Egyptian HCV-infected patients to DAAs.

Association of Interleukin 28B Polymorphism with Clearance of Hepatitis C Virus: A Mini Review.

The highly infectious hepatitis C virus (HCV) is the major cause of chronic hepatitis around the globe. Approximately 3% of the world's population has been affected by both chronic and acute HCV. In this study, we highlight the relationship between single-nucleotide proteins (SNPs) and interleukin (IL) IL28B on chromosome 19 with the treatment response of chronic HCV infection along with its sustained virologic response (SVR). Four SNPs are strongly linked with HCV self-clearance: rs8099917 TT, rs12980275 AA, rs8105790 TT, and rs10853728 CC. Most SNPs, including rs12979860, are located upstream of the IL28B gene fragment, encoding interferon (IFN)-λ3. We find that IL28B variants rs8099917 and rs12979860 strongly influence results of combined pegylated (PEG)-IFN/ribavirin (RBV) therapy. In the case of SNP rs12979860, the CC genotype is linked with greater than a twofold higher SVR than that with TT or CT genotypes. These SNPs are associated with expression of intrahepatic IFN-stimulated genes in liver. Past research shows that females are more efficient in resolving HCV infection, regardless of IL28B genotype. Similar results of IL28B polymorphisms associated with spontaneous HCV clearance were also obtained in Chinese and Taiwanese HCV patients. Another report of RBV and PEG-IFN-treated patients revealed that age, viral load, rs8099917 genotype, and fibrosis were major predictors of antiviral therapeutic response. To select favorable antiviral regimes for treatment using IFN, a combination of host genetic data and viral genotyping may be useful in treating chronic HCV. We propose that these predictive factors must be considered before commencing treatment in HCV patients.

Interleukin 28B Polymorphism as a Predictor of Response to Treatment of Egyptian HCV Patients Working in Nuclear Material Authority

Background: A Single nucleotide polymorphism upstream of the interferon-λ3 gene (IFNL3; formerly referred to IL28B), strongly linked to unprompted and treatment-induced HCV infection clearance. Interleukin 28B genotype predictive value over the outcome interferon-α/ribavirin treatment was assessed carefully and contrasted with virological predictors Objective: The study aimed to evaluate IL-28B rs12979860 polymorphism in the reaction of HCV patients with directacting antiviral (DAA) regimens (sovosbuvir) and ribavirin therapy and the allele frequencies of this gene in Egyptian HCV patients working in the Egyptian Nuclear Materials Authority contrasted to healthy control. Subjects and Methods: The study was conducted on randomly chosen fifty Egyptian patients infected with genotype 4 HCV aged 30 or more and received antiviral therapy (sovosbuvir and ribavirin) before six months or more. Another Fifty age and gender matched apparantely healthy individuals were also selected as a control group. The study was carried out in accordance with the ethical principles and guidelines of the Declaration of Helsinki and a written informed consent was obtained from all subjects. Results:IL-28B genotype CC was found in 34.6% of patients, while CT and TT genotypes were identified in 42.3 and 23.1% of patients, respectively. Forty (40%) patients achieved an SVR, whereas ten (20%) did not. Of the 40 patients with an SVR, 12 had genotype CC, 25 had genotype CT, and 3 had genotype TT. CT genotype patients has achieved considerably higher SVR rates (62.5%) compared with CC (30%) and TT patients (7.5%). Conclusion: Polymorphism Il-28B is an autonomous predictor of SVR to Peg IFN / RBV in patients with genotype 4 in Egyptian HCV favorable.

Interleukin 28B Polymorphism as a Predictor of Response to Treatment of Egyptian HCV Patients Working in Nuclear Material Authority

Background: A Single nucleotide polymorphism upstream of the interferon-λ3 gene (IFNL3; formerly referred to IL28B), strongly linked to unprompted and treatment-induced HCV infection clearance. Interleukin 28B genotype predictive value over the outcome interferon-α/ribavirin treatment was assessed carefully and contrasted with virological predictors Objective: The study aimed to evaluate IL-28B rs12979860 polymorphism in the reaction of HCV patients with directacting antiviral (DAA) regimens (sovosbuvir) and ribavirin therapy and the allele frequencies of this gene in Egyptian HCV patients working in the Egyptian Nuclear Materials Authority contrasted to healthy control. Subjects and Methods: The study was conducted on randomly chosen fifty Egyptian patients infected with genotype 4 HCV aged 30 or more and received antiviral therapy (sovosbuvir and ribavirin) before six months or more. Another Fifty age and gender matched apparantely healthy individuals were also selected as a control group. The study was carried out in accordance with the ethical principles and guidelines of the Declaration of Helsinki and a written informed consent was obtained from all subjects. Results:IL-28B genotype CC was found in 34.6% of patients, while CT and TT genotypes were identified in 42.3 and 23.1% of patients, respectively. Forty (40%) patients achieved an SVR, whereas ten (20%) did not. Of the 40 patients with an SVR, 12 had genotype CC, 25 had genotype CT, and 3 had genotype TT. CT genotype patients has achieved considerably higher SVR rates (62.5%) compared with CC (30%) and TT patients (7.5%). Conclusion: Polymorphism Il-28B is an autonomous predictor of SVR to Peg IFN / RBV in patients with genotype 4 in Egyptian HCV favorable.

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection: An updated meta-analysis.

Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection.PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms “interleukin 28B”, “IFN-lambda-3”, “IFNL3”, “single nucleotide polymorphisms”, “SNPs”, “hepatocellular carcinoma”, “HCC”, “liver cancer”.A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57–0.88; OR = 0.82, 95% CI = 0.72–0.94, respectively). Egger test and Begg test revealed no‘ publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis.Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.

The efficacy of adding vitamin B12 to pegylated interferon and ribavirin treatment in Hepatitis C virus patients regarding the host and viral prognostic factors

Introduction: Hepatitis C virus (HCV) infection affects almost 180 million people around the world. Even though the development of direct acting antivirals (DAAs) has significantly improved the treatment responses to HCV infection, treatment with pegylated interferon (PegIFN) in combination with ribavirin is considered the standard of care (SOC) for chronic HCV infection treatment in countries with limited medical resources. Considering the inhibitory effect of vitamin B12 on HCV replication, we have evaluated the effect of vitamin B12 supplementation along with SOC on treatment outcomes in patients with chronic HCV infection, who were antiviral treatment-naive.&#x0D; Methods: In this regard, seventy-four HCV-infected patients, naïve to antiviral therapy, were randomly assigned to receive SOC or SOC in addition to vitamin B12 (SOC + B12). Viral response was evaluated at 4, 12, 24 and 48 weeks following the initiation of viral treatment and at 24 weeks after completing the treatment. Genotyping of the interleukin 28B (IL28B) polymorphisms was also performed. Demographic characteristics, clinical findings, fibroscan results and drug adverse effects were recorded.&#x0D; Results: Our findings showed that rapid viral response was not significantly different between the two groups; however, the rates of complete early viral response (cEVR) (p=0.033), end-of-treatment viral response (ETVR) (p=0.001) and sustained virologic response (SVR) (p=0.0001) were significantly higher in SOC + B12 patients compared to SOC patients. Besides, in SOC + B12 patients, those with a higher baseline viral load and carriers of IL28B CC genotype showed significantly higher rate of SVR.&#x0D; Conclusion: In conclusion, the addition of vitamin B12 significantly improved the rate of SVR in HCV-infected patients, who were naïve to antiviral therapy. As this treatment regimen is safe and inexpensive, it proposes an option for improving the effectiveness of the HCV treatment with SOC, particularly in resource-limited settings.&#x0D;

Extracellular Matrix Proteins Substantiate IL-28B T allele Effect on Histological Outcome of Chronic Hepatitis C

Introduction and aim. The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease.Material and methods. IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients.Results. Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.961.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively.Conclusion. This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.

P1‐037: Role of interleukin 28B polymorphism in response to interferon based therapy for hepatitis C virus clearance in Libya

Journal of Viral HepatitisVolume 25, Issue S2 p. 45-45 Abstracts P1-037: Role of interleukin 28B polymorphism in response to interferon based therapy for hepatitis C virus clearance in Libya First published: 12 June 2018 https://doi.org/10.1111/jvh.21_12923Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume25, IssueS2Special Issue: 16th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) held from June 14th to 17th, 2018, in Toronto, CanadaJune 2018Pages 45-45 RelatedInformation

Role of Interleukin 28B Polymorphisms in Response to Interferon Based Therapy for Hepatitis C Virus Clearance

Interleukin-28B (IL28B) locus on a human chromosomal region mapped to 19q13 execute immune defense against viruses. During Hepatitis C Virus (HCV) infection the IL28B has a promising role in deciding the consequence of infection for spontaneous clearance of viruses or causing chronic liver infection. Treatment of chronic hepatitis C includes use of direct acting antivirals, Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy. Also, interferon free regimens are suggested to be useful in resistant patients. Numerous reports including Genome-Wide Association Studies (GWAS), comprehensive meta-analysis and independent case-control studies in different population have revealed the association between certain Il-28B polymorphisms and response to the PEGIFN- RBV therapy in patients infected with HCV. We searched all peer-reviewed relevant and recent literature manually for the present review. The GWAS studies have revealed an important role of IL28B in HCV infection, which was supported by many independent studies and meta-analysis by different groups in different ethnicities. IL28B genotyping may be use as predictors of response for IFN-based therapy and personalized treatment of hepatitis C patient.

Pharmacogenetics of the anti-HCV drug sofosbuvir: a preliminary study.

Sofosbuvir is a potent nucleotide HCV NS5B polymerase inhibitor that is also a P-glycoprotein (encoded by the ABCB1 gene) and breast cancer resistance protein (encoded by the ABCG2 gene) substrate. Concerning previous anti-HCV therapies, pharmacogenetics had a significant impact, particularly considering the association of interleukin28B polymorphisms with dual-therapy (ribavirin + pegylated IFN) outcomes. In this work, we investigated the association between sofosbuvir and its prevalent metabolite (GS-331007) plasma concentrations at 1 month of therapy and genetic variants (SNPs) in genes encoding transporters and nuclear factors (ABCB1, ABCG2 and HNF4α) related to sofosbuvir transport. Allelic discrimination was performed through real-time PCR, whereas plasma concentrations were evaluated through liquid chromatography. One hundred and thirteen patients were enrolled. Sofosbuvir concentrations were below the limit of quantification since the drug was converted into its GS-331007 metabolite. ABCB1 2677 G>T (P = 0.044) and HNF4α 975 C>G (P = 0.049) SNPs were associated with GS-331007 metabolite plasma concentrations. In linear multivariate analysis, liver stiffness, insulin resistance, baseline haemoglobin and haematocrit and SNPs in the ABCB1 gene (3435 CT/TT and 1236 TT genotypes) were significant predictors of GS-331007 concentrations. Furthermore, we performed sub-analyses considering the anti-HCV concomitant drug and HCV genotype, identifying specific polymorphisms associated with GS-331007 plasma concentrations: ABCB1 3435 C>T and HNF4α975 C>G in patients treated with daclatasvir, ABCB1 2677 G>T with ledipasvir and ABCB1 3435 C>T, ABCB1 2677 G>T, ABCG2 421 C>A and ABCG2 1194 + 928 C>A with ribavirin. In this study we suggested sofosbuvir GS-331007 metabolite plasma levels were affected by variants in the ABCB1 and HNFα genes.

Distribution of IL28B and IL10 polymorphisms as genetic predictors of treatment response in Pakistani HCV genotype 3 patients.

There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan. For these patients, a combination of interferon with ribavirin is the most economical and easily available treatment. Single-nucleotide polymorphisms in interleukin genes have been reported to be associated with the pathogenesis and clearance of HCV, and sustained virologic response (SVR). An interleukin 28B (IL28B) gene polymorphism has been shown to modify treatment outcomes, but the effects of interleukin 10 (IL10) polymorphisms have not been previously assessed in the Pakistani population. The present study was conducted with 302 subjects categorized into two groups: 100 healthy volunteers (Group I) and 202 patients with chronic HCV (Group II). Patients within Group II were further divided into two subgroups according to therapeutic response: SVR (responders = 132) and NR (non-responders/relapsers = 70). IL28B (rs8099917, rs12979860) and IL10 (rs1800872, rs1800871, rs1800896) gene polymorphisms were studied in all subjects. A significant difference in the distribution of IL28B rs12979860C/T genotypes between the two groups (p<0.05) was observed, while of the three IL10 polymorphisms, a significant difference was only shown for rs1800896 A/G. Haplotype analysis (IL28B and IL10) showed a significant association of TTGTC and TTGTA when comparing the groups. There was a strong association of the favorable alleles rs8099917T and rs12979860C in the SVR group as compared with the NR group (p<0.05), and rs1800896 also showed an association with the SVR group as compared to the NR group (p<0.004). Haplotype analysis showed significant associations when comparing the SVR and NR subgroups, i.e. TCATC (p=0.009), TTGTA (p=0.005), TCATA (p<0.0005), TCACA (p=0.002), GTGCC (p=0.002) and TCGTC (p=0.005). IL28B (rs8099917 and rs12979860) and IL10 (rs1800896) polymorphisms alone, or in combination, are good predictors of therapeutic response in HCV-3a patients.

Changes in liver stiffness measurement using acoustic radiation force impulse elastography after antiviral therapy in patients with chronic hepatitis C.

BackgroundTo compare on-treatment and off-treatment parameters acquired using acoustic radiation force impulse elastography, the Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index (APRI) in patients with chronic hepatitis C (CHC).MethodsPatients received therapies based on pegylated interferon or direct-acting antiviral agents. The changes in paired patient parameters, including liver stiffness (LS) values, the FIB-4 index, and APRI, from baseline to sustained virologic response (SVR) visit (24 weeks after the end of treatment) were compared. Multiple regression models were used to identify significant factors that explained the correlations with LS, FIB-4, and APRI values and SVR.ResultsA total of 256 patients were included, of which 219 (85.5%) achieved SVR. The paired LS values declined significantly from baseline to SVR visit in all groups and subgroups except the nonresponder subgroup (n = 10). Body mass index (P = 0.0062) and baseline LS (P < 0.0001) were identified as independent factors that explained the LS declines. Likewise, the baseline FIB-4 (P < 0.0001) and APRI (P < 0.0001) values independently explained the declines in the FIB-4 index and APRI, respectively. Moreover, interleukin-28B polymorphisms, baseline LS, and rapid virologic response were identified as independent correlates with SVR.ConclusionsPaired LS measurements in patients treated for CHC exhibited significant declines comparable to those in FIB-4 and APRI values. These declines may have correlated with the resolution of necroinflammation. Baseline LS values predicted SVR.