IL28B Rs12979860 Research Articles

The Pre-/Post-Transplant Hepatitis C Antibody Associated with the IL-28B RS8099917 TT Genotype and miRNA-122 Expression May Protect Acute Cellular Rejection After LDLT.

This study aimed to investigate the relationship between the IL-28B SNP rs8099917 genotype, miRNA-122 expression, and the immune mechanism of ACR after LT using anti-HCV antibody calibration. A total of 45 patients with HCV received LT. IL-28B SNP rs8099917 genotyping was used to divide patients into TT and GT groups. The relative expression levels of miRNA-122 were calculated by quantitative PCR. Anti-HCV titers before and after LT were tracked to observe the relationship with ACR. The ACR rates were 27.6% for genotype TT and 62.5% for genotype GT, indicating a significantly higher rate in the GT group compared to the TT group (p = 0.024). In the rs8099917 genotype, TT was significantly associated with higher serum miRNA-122 levels than GT (p < 0.001). The TT group had significantly better outcomes than the GT group (p = 0.005). The Mann-Whitney U test showed significant differences in pre-LT and post-LT anti-HCV titers between the IL-28B genotypes (TT and GT) (p values of 0.006 and 0.027, respectively). These results suggested that the IL-28B rs8099917 genotype TT may play a significant role in modulating immune responses, both in terms of anti-HCV titers and the risk of ACR, possibly mediated through miRNA-122 levels.

Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients.Graphical abstract

Prediction Model for the Clearance of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B before Interferon Therapy: A Prospective Case-Control Study.

To evaluate the prediction model comprised of patients' laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case-control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030-0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768-71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006-0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040-0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138-13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.

IL28B rs12979860 gene polymorphism and sofosbuvir-based therapy response in HCV-infected Pakistani patients

IL28B rs12979860 gene polymorphism and sofosbuvir-based therapy response in HCV-infected Pakistani patients

Impact of IL28B (rs8099917) gene polymorphism on treatment response to Sovaldi, Daklinza, and Ribavirin in Egyptian patients with HCV infection

ABSTRACT Infection by the hepatitis C virus (HCV) is a big threat to human health all over the world. Many host factors could affect the treatment response in HCV infection. One of these factors is IL28B gene polymorphism. This research study investigated the association of IL28B (rs8099917) gene polymorphism with treatment response in patients with chronic hepatitis C virus (HCV) infection receiving a combination of Sovaldi, Daklinza, and Ribavirin in Egypt. The study included 100 patients, divided into three groups based on treatment outcomes: responders, relapsers, and non-responders. Biochemical and hematological analyses were performed, and HCV genotypes were determined using PCR. IL28B genotyping was done using real-time PCR. The results showed a high prevalence of HCV genotype 4 and a few patients with genotype 1. The G allele of IL28B was associated with a higher risk of developing relapse and non-response, while the TT genotype was significantly associated with treatment success. Viral load levels were lower in responders compared to relapsers and non-responders. The study suggests that IL28B genotype may be a valuable predictor of treatment response in chronic HCV patients treated with the specified combination therapy. Further research is needed to confirm and fully understand these findings.

Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia

Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.

Генетический полиморфизм воспалительных цитокинов в крови пациентов с инвазией Opisthorchis felineus

Aim: To research the relationship between laboratory and instrumental manifestations of pathology and polymorphisms of inflammatory cytokine genes in patients with Opisthorchis felineus invasion. Design. During 2022, we conducted a comparative study of patients who were hospitalized for etiotropic therapy of O. felineus invasion. Materials and methods. 139 patients with O. felineus invasion were examined. All patients underwent clinical and biochemical blood tests, ultrasound of the abdominal organs and liver elastometry with an assessment of liver fibrosis according to the METAVIR scale. Genotyping of single nucleotide polymorphisms of the IL28b, IL6, TNFA, and IFNG genes was performed using real-time PCR. Results. In patients with opisthorchiasis, liver fibrosis was associated with the presence of the minor allele A of the rs1800630 TNFA polymorphism and the TC genotype of rs2069705 IFNG. Polyps in the gallbladder were associated with the CC genotype of rs1800630 TNFA, while an increase in alkaline phosphatase and an increase in the proportion of eosinophils in the blood were associated with the CC genotype of rs2069705 IFNG. We did not find differences in the studied parameters depending on the genetic polymorphisms rs12979860 IL28b and rs1800795 IL6 in patients with O. felineus invasion. Conclusion. The obtained regularities should be used to increase the efficiency of dispensary observation in order to prevent the development of complications of parasitic invasion. Keywords: Opisthorchis felineus, single nucleotide polymorphism, cytokines, liver fibrosis.

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.

Treatment of Hepatitis C Disease with Standard Therapy and its Correlation with Specific Genotype of Interleukin

Aim: To determine the association of interleukin-28b- RS12980275 with response to treatment with interferon α-2b &amp; ribavirin in chronic hepatitis c patients Methodology: A case control study was designed that includes219 HCV patients treated with INF and Ribavirin. Out of 219, 95 were males while 124 were females. They are classified into two groups. Those achieved sustained virological response (SVR) and those who did not sustained virological response (Non-SVR). All the demographics and biochemical data were recorded on a Performa that includes age, ALT and viral load. The data were analyzed using SPSS version 16.0. Results: Patients having IL28B-rs12980275 AG genotypes respond better to interferon and ribavirin treatment (p-value=0.01, OR=2.91). Furthermore, HWE was also calculated for both groups in which the responders do not corresponds to HWE (p-value= &lt;0.001) while the non-responders were found to be consistent with HWE (p-value= 0.31). Conclusion: Polymorphism in IL28B (rs12980275) was found to be significantly associated (p-value = 0.009) with the treatment outcome in patient with hepatitis C receiving standard therapy regimen (Interferon + Ribavirin). Key words: Hepatitis C, polymorphism, Interferon

Association between Psoriasis Disease and IFN-λ Gene Polymorphisms

ABSTRACT Psoriasis is one of the most common chronic immune-mediated skin diseases, having a strong genetic predisposition. Psoriasis is a T-cell-mediated disease with a mixed Th1/Th17 cytokines environment. IL-23/IL-17 axis hyperactivation is the primary pathogenesis. Psoriasis lesions have been known to exhibit high IFN-λ1 and IFN-stimulated genes (ISGs) expression, which appears to be driven by Th17 cells. However, the role and mechanism of IFN-λs in psoriasis disease remains unknown. The study aimed to investigate the relationship between IL-28B and IL-29 gene polymorphisms with psoriasis disease and clinical severity. We performed single-nucleotide polymorphisms (SNPs) of IL-28B rs12979860 (IL-28 C/T), rs8099917 (IL-28 T/G), and IL-29 rs30461 (IL-29 T/C) in 140 patients with psoriasis disease and 159 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequency distributions of the rs12979860 (IL-28 C/T) and rs30461 (IL-29 T/C) polymorphisms were similar in the patient and control groups and were not statistically significant. The TG genotype of rs8099917 was statistically significantly different in patients from both groups. The TG genotype increased the risk of disease1.9-fold. The G allele may be associated with the pathogenesis of psoriasis.

The effects of IL28B rs12979860 and rs8099917 polymorphism on Hepatitis B infection

The purpose of this study was to evaluate the relationship of IL28B rs12979860 and rs8099917 polymorphisms with the clinical, histological, and virological outcomes of patients with chronic hepatitis B (CHB) also the treatment responses of patients who received Nucleos(t)ide analogs (NAs) therapy. This study included 152 CHB patients who were underwent liver parenchymal biopsy. The IL28B rs12979860 and rs8099917 polymorphism were genotyped using the TaqMan assay. The IL28B rs12979860 CC and IL28B rs8099917 TT were identified as the genotypes with the highest frequency in all patients. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency. The frequency of IL28B rs8099917 TG genotype was significantly different between patients with hepatitis B, who has histologically defined liver cirrhosis and no-fibrosis (p=0.02). In addition, a statistically significant correlation was found between the presence of IL28B rs8099917 G allele and virological unresponsiveness to NAs treatments in CHB patients (p=0.028). The presence of the IL28B rs8099917 G allele in CHB patients might be associated with the risk of developing cirrhosis and virological unresponsiveness to NAs treatments.

IL28B rs12979860 and rs8099917 polymorphisms in patients with chronic hepatitis C and non-viral liver disease

IL28B rs12979860 and rs8099917 polymorphisms in patients with chronic hepatitis C and non-viral liver disease

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P&lt;0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (?400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Single Nucleotide Polymorphisms of Interleukins and Toll-like Receptors and Neuroimaging Results in Newborns with Congenital HCMV Infection.

Congenital cytomegalovirus infection (cCMV) is the most common intrauterine infection with central nervous system (CNS) involvement. There is limited data on the associations between Single Nucleotide Polymorphisms (SNPs) in genes involving the first-line defense mechanism and the risk of CNS damage during cCMV. We investigated the associations between neuroimaging findings and SNPs in genes encoding the following cytokines and cytokine receptors in 92 infants with cCMV: interleukins (IL1B rs16944, IL12B rs3212227, IL28B rs12979860), C-C motif chemokine ligand 2 (CCL2 rs1024611), dendritic cell-specific intercellular adhesion grabbing non-integrin (DC-SIGN rs735240), Toll-like receptors (TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140). The SNP of IL1B rs16944 (G/A) was associated with a reduced risk of ventriculomegaly on MRI (OR = 0.46, 95% CI, 0.22–0.95; p = 0.03) and cUS (OR = 0.38, 95% CI, 0.0–0.93; p = 0.034). Infants carrying heterozygous (T/C) genotype at IL28B rs12979860 had an increased risk of cystic lesions on cUS (OR = 3.31, 95% CI, 1.37–8.01; p = 0.0064) and MRI (OR = 4.97, 95% CI, 1.84–13.43; p = 0.001), and an increased risk of ventriculomegaly on MRI (OR = 2.46, 95% CI, 1.03–5.90; p = 0.04). No other associations between genotyped SNPs and neuroimaging results were found. This is the first study demonstrating new associations between SNPs of IL1B and IL28B and abnormal neuroimaging in infants with cCMV.

Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection.

BackgroundThere are limited data on factors that determine viral load (VL) in congenital cytomegalovirus (cCMV) infection. Single nucleotide polymorphisms (SNPs) might influence individual host response to infection. This study aimed to investigate the association between SNPs in genes encoding cytokines or cytokine receptors and VL in newborns with cCMV.Material and methodsEight polymorphisms (IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791 and TLR9 rs352140) were analyzed in study population of 233 newborns, including 92 cCMV-infected newborns (73 symptomatic and 19 asymptomatic) by TaqMan SNP Predesigned Genotyping Assays. The association analysis was performed using SNPStats software and STATISTICA10.ResultsThe association between IL12B polymorphism and viruria was observed (p = 0.029). In multiple comparison tests, heterozygous T/G genotype of IL12B was associated with higher viruria than T/T genotype (p = 0.041) in cCMV-infected newborns. In allele analysis, T allele of IL12B was associated with higher viremia (p = 0.037) in symptomatic newborns. We observed higher VL in symptomatic newborns in comparison to asymptomatic (median viremia: 1.7 × 104 copies/mL vs. 2.0 × 103 copies/mL (p = 0.002), median viruria: 1.0 × 107 copies/mL versus 6.9 × 105 copies/mL (p = 0.001), respectively).ConclusionsIL12B rs3212227 was associated with VL in cCMV. Symptomatic newborns had significantly higher viremia and viruria. The role of SNPs in pathogenesis of cCMV warrants further investigations.

Correlation between IL-28 polymorphism and spontaneous clearance in HCV patients: systematic review and meta-analysis.

Hepatitis C virus (HCV) is a serious global health issue. Nearly 20% of HCV patients spontaneously clear the virus. While some studies have shown an association of spontaneous clearance (SC) of the virus with interleukin (IL) 28B single-nucleotide polymorphisms (SNPs), others did not show such a relationship. Thus, the purpose of the present study was to investigate the association of IL28B polymorphisms (12979860 SNP) with SC of HCV infection. Upon initial screening of the databases, a total of 545 articles were retrieved, of which 22 studies that met predefined eligibility criteria were entered into the meta-analysis. Odds ratios (ORs) with confidence intervals (95% CI), heterogeneity, publication bias, and sensitivity analysis were assessed. According to the meta-analysis results, a significant association was observed between the rs12979860 SNP and SC of HCV infection. The results indicated that the ORs of SC from hepatitis C virus infection were 2.75 times higher in those with cytokine gene polymorphisms (95% CI, 2.23 to 3.38). Moreover, it was found that the prevalence of rs12979860 CC was 0.33 with 95 CI 0.28-0.38 in genotype 1 and was 0.40 with 95 CI 0.34-0.47 in other genotypes. Our meta-analysis results suggest that IL28B rs12979860 CC is a strong predictor for SC of hepatitis C infection in PEG IFN-a/RBV-treated patients.

Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis

BackgroundPrevious studies suggested, variations in the IL28B gene can serve as predictors of sustained and rapid virological responses (SVR and RVR) in the treatment of HCV with pegylated interferon and ribavirin (pegINF-RBV) among HCV-HIV co-infected patients. Here, we explored the correlation between IL28B variants (rs12979860, rs8099917 and rs12980275) and treatment response for HCV among co-infected individuals using meta-analysis. MethodsRelevant studies were retrieved from PubMed, EBSCO, ISI Web of Knowledge, Cochrane databases, and the role of IL28B variants on SVR and RVR in co-infected patients treated with pegINF-RBV was evaluated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fixed- and random-effects models. ResultsForty-three studies consisting 3499 patients who achieved SVR/RVR and 4308 non-responders were included in our study. The CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, were associated with SVR in the recessive model for all HCV genotypes: rs12979860, OR = 3.18 [95% CI (2.66, 3.79)]; P < 0.0001; rs8099917, OR = 3.6`9 [95% CI (2.74, 4.97)]; P < 0.0001; rs12980275, OR = 2.97 [95% CI (2.26, 3.89)]; P < 0.0001. Significant association of rs12979860 CC genotype with RVR was also found: OR = 2.31 [95% CI (1.54, 3.57)]; P < 0.0001. Stratification analysis of HCV genotypes revealed similar trends of association with the rs12979860 CC genotype for HCV-1, HCV-1/4 and HCV-4, but no association was found for HCV-2/3 and HCV-3. ConclusionsOur meta-analysis suggests that the CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, are strong predictors for SVR, and the rs12979860 CC genotype has significant RVR predictive value in HCV-HIV co-infected patients treated with pegINF-RBV.

Pegylated interferon and ribavirin gone but not forgotten in the era of direct-acting antivirals.

Therapy with pegylated interferon and ribavirin (PEG-IFN+RBV) for chronic hepatitis C (CHC) remains the only option available for children in many Eurasian and European countries. Our aim was to evaluate the influence of host and viral factors on response to IFN-based therapy to optimize it for those in whom directly acting antivirals (DAA) are currently unavailable. Seventeen vertically infected, treatment naive children (10 male and 7 female) aged 5-16 years with CHC underwent a course of PEG-IFN+RBV. The end point was sustained virologic response (SVR). Host and virus factors were divided into pre- and on-treatment predictors of response to therapy. Eleven patients obtained SVR (64%), 4 were non-responders (23%), and 2 were relapsers (12%). Significant relationship was found between HCV RNA elimination and following variables: virus genotype and early virologic response (EVR) (P<0.037, P<0.029 respectively). Higher eradication rate was observed in patients infected with genotype 3 HCV (100% vs. 65% with genotype 1 or 4), and in those with undetectable HCV RNA by week 12 (88% vs. 66% with viremia). EVR was associated with SVR (83% vs. 0% in nonresponders; P<0.004). C allele of IL28B rs12979860 was a predictor of EVR (P<0.043). The SVR rates among CC, CT, and TT carriers were as follows: 75%, 67%, and 33%. Detection of favorable HCV and IL28B genotype prior to commencement of PEG-IFN+RBV and continuing it in patients with EVR is of major importance for those in whom DAA are still unavailable.

The relation between interleukin 28B gene polymorphisms (rs8099917 and rs12980275) and the response of treatment of Hepatitis C Virus genotype 4 patients to Sofosbuvir and Daclatasvir therapy

Background: The main line of treatment of hepatitis C in Egypt is direct acting antiviral drugs (DAAs) Objectives: the current study aimed to explore the effect of IL28B genetic polymorphism on HCV infection progression and response to the new treatment in difficulty to treat individuals with HCV genotype 4. Methods: we collected blood samples from 50 healthy individuals as a control and 150 HCV- patients receiving SOF/DCV with ribavirin combination. IL28B (rs8099917, rs12980275) genotyping was implemented using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method to detect its impact on HCV disease outcome. Results: Out of patients, 141(94%) were responders to treatment and 9 (6%) were non- responders. A total of 112 (74.7%) of patients belonged to mild to moderate stages of liver fibrosis and 38(25.3%) had moderate to severe stages. There was a significant increase in severity of fibrosis among non-responders (p value .0.05). significant differences between the different genotypes of IL28B rs12980275 are not detected among the study population. Conclusion: TT genotype of IL28B (rs8099917) may be a protective factor against infection and associated with probability of achieving SVR to combined SOF and DCV therapy in genotype 4 HCV patients. However, GG genotype is negatively associated with HCV infection outcome. IL28B rs12980275 variants had no association with HCV infection.