IL28B Rs12979860 Polymorphism Research Articles

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.

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.

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<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.

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

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.

Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection

Congenital cytomegalovirus (cCMV) infection is the most common intrauterine infection. A non-specific immune response is the first line of host defense mechanism against human cytomegalovirus (HCMV). There is limited data on associations between Single Nucleotide Polymorphisms (SNPs) in genes involving innate immunity and the risk and clinical manifestation of cCMV infection. The aim of the study was to investigate association between selected SNPs in genes encoding cytokines and cytokine receptors, and predisposition to cCMV infection including symptomatic course of disease and symptoms. A panel of eight SNPs: IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140 was analyzed in 233 infants (92 cCMV-infected and 141 healthy controls). Associations between genotyped SNPs and predisposition to cCMV infection and symptoms were analyzed. The association analysis was performed using SNPStats software. No statistically significant association was found between any genotyped SNPs and predisposition to cCMV infection and symptomatic course of disease. In relation to particular symptoms, polymorphism of IL12B rs3212227 was linked to decreased risk of prematurity (OR = 0.37;95%CI,0.14-0.98;p = 0.025), while polymorphism of IL1B rs16944 was linked to reduced risk of splenomegaly (OR = 0.36;95%CI,0.14-0.98; p = 0.034) in infants with cCMV infection. An increased risk of thrombocytopenia was associated with IL28B rs12979860 polymorphism (OR = 2.55;95%CI,1.03-6.32;p = 0.042), while hepatitis was associated with SNP of TLR4rs4986791 (OR = 7.80;95%CI,1.49-40,81; p = 0.024). This is the first study to demonstrate four new associations between SNPs in selected genes (IL1B, IL12B, IL28B, TLR4) and particular symptoms in cCMV disease. Further studies on the role of SNPs in the pathogenesis of cCMV infection and incorporation of selected SNPs in the clinical practice might be considered in the future.

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C.

Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients' sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B - TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 - 18.297, p=0.024). IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

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.

Relation of IL28B Rs12979860 Polymorphism on Depression Symptoms in the Treatment of Chronic Hepatitis C

AIM: The presente study we aim to evaluate the relationship between the single nucleotide polymorphism (SNP) rs12979860 in the IL28B gene with the diagnosis of depression and its symptoms along the treament of HCV patients. Material and Methods: Is a convenience cohort where patients were follow-up by 12 weeks during the antiviral therapy. A sociodemographic questionnaire, psychiatric diagnostic interview and laboratorial data were applied at the baseline, 4th week and 12th week of treatment. A sample of buccal cells was collected from each patient in the baseline and IL28B rs12979860 (C/T) polymorphism was genotyped by real-time PCR. Results: 90 patients were evaluated in relation to IL28B rs12979860 (C/T) polymorphism. The rs12979860 polymorphism were not significantly associated with the diagnoses of major depression (p = 0.186) in the baseline, but along the treatment the T allele present a risk factor for irritability OR 3.75 [CI (1.22-11.57); p = 0.021]. Past depression is associated with the diagnosis of current depression pre treatment (p = 0.018). Conclusion: Our results suggest that patients carrying T-allele of rs12979860 have worst symptoms of depression related to those with CC genotype. These results indicate that genotypes of IL28B rs12979860 polymorphism should be better studied to be considered for further treatment.

Factors related to fatalities and clinical progression of Crimean-Congo hemorrhagic fever patients and the effects of IL 28-B gene polymorphism

Mortality rates of Crimean-Congo hemorrhagic fever (CCHF) vary from 5% to 80%. However, there is no clear information available about why this disease is fatal for some people while others recover. In this study, the factors related to fatalities and serious clinical progression of CCHF patients and the correlation between serious prognosis and IL 28-B gene polymorphism were investigated. The study included 107 patients with a preliminary diagnosis of CCHF, and the patients were found positive for CCHFV RNA based on polymerase chain reaction (PCR) analysis. The IL 28-B rs12979860 polymorphism was identified by PCR "restriction fragment length polymorphism" (PCR-RFLP) analysis using blood samples from the patients. In addition to the IL 28-B analysis results, a variety of data along with laboratory records obtained during the hospital stay were evaluated using statistical analysis. Of the 107 cases, nine were fatal (8.4%), while the other patients recovered and were discharged. Twenty-four patients had the CC genotype (22.43%), 64 had the CT genotype (59.81%), and 19 had the TT genotype (17.76%). Of the nine patients who died, three had the CC genotype (33.33%) and six had the CT genotype (66.67%). None of the patients who died had the TT genotype. Symptoms and findings of diarrhea, abdominal pain, hemorrhage, and rash were more common in fatal cases than in non-fatal cases. The IL 28-B rs12979860 polymorphism was not found to have a statistically significant correlation with fatality or symptoms indicating serious clinical progression in CCHF patients. As has been observed in previous studies, our study showed that leukocytosis, abdominal pain and diarrhea were more common in fatal cases.

IL-28B rs12979860 polymorphism affect the course of chronic hepatitis and the development of HCC in Egyptian patients with hepatitis C type 4

ABSTRACTBackground: A single nucleotide polymorphism (SNP) in the interleukin 28B (IL28B) gene may alter the trajectory of hepatitis C virus (HCV) chronic infection. Several studies have sought to determine a link between IL28B rs12979860 SNP and the development of HCV-related hepatocellular carcinoma (HCC), but with variable results, and consensus is awaited. We hypothesised that IL28B rs12979860 SNP is linked to HCC in patients with HCV type 4.Methods: IL28B genotyping of 300 patients with HCV-related fibrosis (n = 100), cirrhosis (n = 100) and HCC (n = 100) was carried out and the results were analysed to determine the association between the IL28B genotype and clinical outcome.Results: In IL28B TT genotype carriers, the proportions of moderate/severe fibrosis, advanced cirrhosis (Child B-C) and HCC (50%, 84% and 60.2%, respectively) were higher (p < 0.05) than in CC/CT (4.3%, 46% and 23%, respectively). IL-28B SNP was linked significantly (p < 0.05) with cirrhosis progression and HCC advanced stages. Moreover, HCC advanced Child, Okuda and CLIP stages were associated with T allele carriage (73.9%, 82.6% and 78.3% vs. 44.2%, 50.6% and 46.8% in CC/CT). The percentage of large tumour size (> 3cm) increased (p = 0.028) in TT genotype carriers (81.8% vs.52.6% in CC/CT).Conclusion: IL-28B rs12979860 TT genotype is more prevalent in patients with advanced fibrosis, cirrhosis and HCC stages. Thus, it seems to be associated with poor outcomes in chronic HCV patients and to augment the risk of developing HCC.

Host Factor Predictors in Long-term Nonprogressors HIV-1 Infected with Distinct Viral Clades.

HIV-1+ long-term nonprogressors (LTNPs) maintain natural control of viral infection. This study sought to identify and characterize HIV- LTNPs series case, regarding the presence of possible host factors that may be associated with this status. We evaluated the plasma levels of IP-10/IL-8 chemokines, HLA-B alleles, and IL28B rs12979860 polymorphism in 24 LTNPs who presented with infection by different clades of HIV-1. IL-8 chemokine was significantly higher in progressors than in LTNPs, but there was no difference between the LTNP subgroups. There was a negative correlation in CD4+ T cell (TC) count and IL-8 dosage, and a positive correlation with CD8+ TC. IP-10 chemokine levels were associated with viremia, and the elite controller (EC) subgroup showed nearly the same level than healthy individuals and progressors with viral load suppressed. Furthermore, the CD4+ TC count, percentage of CD4+ TC, and CD4/CD8 ratio were negatively correlated with IP-10. No association was found in plasma levels of IL-8 and IP-10 chemokines and HIV-1 clades. In the EC/viremic controller subgroup, 80% presented with at least one HLA-B allele previously considered as potentially protective for AIDS progression. No association was observed between the HLA-B alleles and HIV- 1 clades. The IL28B CC genotype was identified in 87.5% of LTNPs. In this LTNP series case we observed different host factors that may be contributing to their nonprogressor status, and the association of these factors with the control of infection progression may be critically important for future therapeutic and prophylactic options in HIV-1 infection.

Distribution of IL28B rs12979860 and rs8099917 Genotypes in Patients with Chronic Hepatitis C Virus Infection in Tianjin, China.

Two single-nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G), near the interleukin 28B (IL28B, also known as IFN lambda-3, IFNL3) gene, have a strong association with both spontaneous and treatment-induced hepatitis C virus (HCV) clearance. IL28B polymorphisms have shown a marked differential distribution with regional and ethnic variation. The study aimed to investigate the distribution of IL28B rs12979860 and rs8099917 genotypes in patients with chronic hepatitis C (CHC) in Tianjin, China. A total of 1,600 patients with chronic HCV infection were enrolled, including 762 males and 838 females. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped via a DNA microarray-based assay. The distribution of IL28B rs12979860 CC, CT, and TT genotypes was 93.94%, 5.94%, and 0.12%, and that of rs8099917 TT, TG, and GG genotypes was 88.75%, 11.06%, and 0.19%, respectively. The allele frequencies for rs12979860 C and T were 96.91% and 3.09%, and those for rs8099917 T and G were 94.28% and 5.72%, respectively. The combined assessment of the two SNPs showed that rs12979860 CC/rs8099917 TT was more prevalent with a frequency of 85.94% (1375/1600). When stratified with gender, the genotype and allele distribution of the two SNPs did not significantly differ between male and female subjects. When compared with the data derived from previously reported studies and the 1000 Genomes Project, there was a relatively higher distribution of favorable genotypes rs12979860 CC and rs8099917 TT in the present study. IL28B rs12979860 CC and rs8099917 TT genotypes were predominant in patients with chronic HCV infection in Tianjin, China. These data provided new insight into the geographical frequency distribution of IL28B variants. The higher distribution of the favorable genotypes in Tianjin might be suggestive of better response to antiviral therapy for interferon-eligible CHC patients in this resource-constrained area.

Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C without sustained response to combination therapy.

Although antiviral therapy reduces development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC), HCC often develops in patients with non-sustained virologic response (non-SVR). We aimed to evaluate risk factors for HCC in HCV patients with non-SVR. From March 2002 to December 2013, 800 patients with CHC who had received combined pegylated interferon (peg-IFN)/ribavirin (RBV) therapy without achieving SVR were enrolled. Main outcome measure was HCC development. Variables were cirrhosis, platelet count, α-fetoprotein (AFP) levels, aspartate aminotransferase (AST) to platelet ratio index (APRI), and IL28B polymorphism (CT+TT). One-hundred of 800 non-SVR patients developed HCC within a median 53.5-months follow-up. Cumulative incidence of HCC for all patients was 1.4%, 5.6% and 12.3%, respectively, at 1st, 3rd and 5th years of follow-up. In univariate analysis, patients who developed HCC tended to have LC (p<0.001), lower platelet counts (<150×109/l, p<0.001), higher AFP levels (≥20ng/ml, p<0.001), higher Fib-4 levels (p<0.001), higher APRI levels (p<0.001), IL 28B polymorphism (CT+TT) (p<0.001) and higher incidence of diabetes mellitus (DM) (p=0.019). Multivariate analysis in overall patients revealed that cirrhosis (HR: 2.94, 95% CI: 1.81-4.77,p<0.001), IL28B rs12979860 (CT+TT) polymorphisms (HR: 3.22, 95% CI: 2.17-4.78, p<0.001), and high APRI levels (≥2.57) (HR: 2.32, 95% CI: 1.47-3.67, p<0.001) were independent risk factors for HCC. Liver cirrhosis, high APRI levels, and IL28B rs12979860 at baseline are independent risk factors for HCC development in patients without SVR after peg-IFN combination therapy.

Association Between IL-28B Polymorphism and Clinical Laboratory Features in Patients with Chronic Hepatitis D

Objectives: We aimed to determine an association between IL-28B rs12989760 single nucleotide polymorphism (SNP) and clinical laboratory parameters in patients with chronic hepatitis D. Methods: A total of 59 patients who were chronically infected with HDV were had their serum tested for the presence of qHBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV, anti-HDV IgM, anti-HDV IgG, HDV RNA, HBV DNA and AFP. Liver function tests, coagulation tests and CBC were also performed. IL-28B polymorphism was performed using a TaqMan 5' allelic discrimination assay by real time PCR. Results: Of these 59 patients, 40 patients (67.8 %) carried the rs12979860CC homozygote genotype, 11 patients (18.6%) were rs12979860CC homozygote and 8 patients (13.6%) were rs12979860CT heterozygote. Alkaline phosphatase and direct bilirubin values were higher (p&lt;0.05) and total protein levels were lower (p&lt;0.05) in patients who were homozygotes for the T allele as opposed to the carriers of the C allele. AFP levels were significantly higher (p=0.02) in the rs12979860 TT genotype group. Liver enzymes including AST, ALT and GGT were significantly not higher in patients who carry C allele (p&gt;.05). Conclusion: The most frequent genotype was IL-28B rs12979860CC among patients with chronic hepatitis D. The IL-28B rs12979860 polymorphism was associated with some abnormal liver function test parameters and AFP levels. Additional studies are necessary to understand the immune mechanisms of IL-28B polymorphism in HDV infection.

Vitamin D receptor polymorphisms as predictors of response to interferon/ribavirin-based therapy in Egyptians with chronic hepatitis C infection

Objective The aim of the present study was to assess the influence of polymorphisms in vitamin D receptors (VDRs) Fok1 and Apa1 and interleukin 28B rs12979860 C/T on the response to interferon/ribavirin-based therapy in Egyptians with chronic hepatitis C. Background Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus. Genetic polymorphisms affecting the VDR gene have been implicated in several immune disorders. Patients and methods This retrospective study was conducted on 80 patients who were divided into two groups: group I – the nonresponders group – comprised 40 patients and group II – the sustained virological response (SVR) group – also comprised 40 patients. The present study also included 20 healthy volunteers as controls. Two single nucleotide polymorphisms in VDRs Fok1 and Apa1 and in IL28B rs12979860 C/T) were determined by real-time PCR and restriction fragment length polymorphisms. Results Genotypes of IL28B rs12979860 (CC/CT/TT) were found in 23 (57.5%), 15 (37.5%), and two (5%) patients and of Apa1 (CA/AA/CC) in 24 (60%), 14 (35%), and two (5%) patients. Genotypes of Fok1 (TT/CC/TC) were found in 23 (57.5%), nine (22.5%), and eight (20%) patients, respectively, in the SVR group. Regarding IL28B rs12979860 polymorphisms, patients with a T-allele carrier had higher frequency among nonresponders (87.5%) in comparison with SVR (42.5%). Regarding VDR (Fok1) polymorphisms, patients with a C-allele carrier had higher frequency among nonresponders (92.5%) in comparison with SVR (42.5%). Regarding VDR Apa1 polymorphisms, patients with a C-allele carrier had higher frequency among nonresponders (92.5%) in comparison with SVR (65%). Conclusion Pretreatment vitamin D level was significantly higher in responders, and this can be used as a predictor of response to combination therapy for hepatitis C virus. VDR gene polymorphisms (Fok1 and Apa1) and IL28B rs12979860 polymorphism are independently related to response to interferon/ribavirin-based therapy in chronic hepatitis C.

Study of Interleukin IL-28B rs12979860 and rs8099917 Polymorphisms among HBV Infected Egyptian Patients

Background: HBV is a worldwide health problem as about 2 billion individuals have been infected with HBV and 350 million are the chronic carriers. The efficacy of anti-viral drugs used in treatment of HBV is high but these drugs are expensive, associated with many side effects and drug resistance was reported. Thus selection of patients with the highest probability of response is essential for clinical practice. Recent genome-wide association studies have revealed some polymorphisms near IL-28B region to be associated with HBV susceptibility, response to treatment or even spontaneous HBV clearance. Objective: This study aimed to investigate role of IL-28B single nucleotide polymorphisms among CHB Egyptian patients. Methodology: SNPs of IL-28B (rs12979860 and rs8099917) regions were genotyped using the MGB-TaqMan SNP genotyping assay in 60 HBV infected patients and 20 healthy volunteers. Results: IL-28B rs12979860 genotypes were expressed in similar proportions in all the studied groups and no statistical significant difference between them was found (MCP=0.272). Concerning IL-28B rs8099917 SNP; GG genotype was 90% expressed among healthy volunteers, while GT genotype was 80% expressed in naive HBV patients, and TT genotype was expressed in 10% non- responder HBV patients only. There was statistical significant difference between the studied groups as 80% of patients in the naive group were carrier to IL-28B rs8099917 GT allele (P=0.013). Conclusion: Genetic variations of IL-28B rs8099917 could be associated with HBV risk and resistance to treatment with nucleoside/ nucleotide analogues as G allele could be protective against HBV, GT genotypes could be risk factor for HBV infection while T allele may be predictive factors of treatment resistance.

Impact of interleukin 28B rs12979860 C/T polymorphism on severity of disease and response to treatment in hepatitis delta.

Pegylated-interferon alpha (Peg-IFN α) is the therapy most commonly used to treat chronic hepatitis delta virus (HDV) infection. In the present study, we planned to investigate effect of IL28B polymorphism on response to Peg-IFN α therapy and disease progression in patients with chronic HDV. A total of 47 patients who received Peg-IFNα therapy for at least one year were investigated. The patients were divided into three groups based on their response to treatment: sustained viral response (SVR) (32%), unresponsive (53%), and relapse (15%). The groups were compared in terms of age, gender, blood biochemistry (albumin, total bilirubin, lactic acid dehydrogenase, ALT, AST, ALP, GGT), complete blood count, HBeAg, HBsAg, HBV-DNA, HDV-RNA, IL28B genotypes (CC, CT, TT), and results of liver biopsy. Regarding the investigation of IL28B genotype, the prevalence of CC, CT, and TT showed no difference among the three groups. In the SVR group, the prevalence of CC was 53%, CT was 47%, but there was no patient with TT. In the unresponsive group, prevalence of CC was 52%, CT was 32%, and TT was 16%. In the relapse group, prevalence of CC was 43%, CT was 57%, but there was no patient with TT genotype. No significant difference was found among the groups with sustained response, no response, and relapse in terms of CC and CT polymorphisms (p>0.05). No relationship was found between IL28B rs12979860 polymorphism and response to treatment and disease severity in patients with chronic HDV infection.

Interleukin-28B Polymorphism is a Pharmacogenetic Predictor during Sofosbuvir Plus Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C Egyptian Patients

Background and Aim: Interleukin-28B (IL-28B) polymorphism is a predictor of sustained virologic response (SVR), spontaneous clearance and personalizing therapy of hepatitis C virus (HCV). This study aimed to determine IL28B rs12979860 polymorphism among chronic hepatitis C (CHC) Egyptian patients as a step in personalized HCV therapy and pharmacogenomics. Methods: CHC Egyptian patients were received sofosbuvir (SOF) plus pegylated interferon (PEG-IFN) and ribavirin (RBV) for 12 weeks. A total of 82 HCV infected Egyptian patients and 27 healthy individuals were included in the present study. CHC Patients were classified as achieving SVR if plasma HCV-RNA was undetectable (group A) and non-responders if plasma HCV-RNA was detectable (group B). IL28B genotypes were analyzed and their associations with SVR were selected. Results: The end of treatment response (ETR) rate was 100%. However, SVR12 was 76.8% (group A) and 23.2% relapsed (group B). Among studied CHC patients, 50% were IL-28B TT, 40.2% CT, and 9.8% CC. while the percentage of their frequencies in the healthy persons were 18.5%, 51.8%, and 29.6%, respectively. These results showed that the frequencies of TT genotypes were more prevalent in HCV patients. The genotype CC (n=8) achieved higher rates of SVR in group A (87.5%) than relapsed patients in group B (12.5%) and it had the least prevalence in group B compared with the frequencies of CT (21.2%) and TT (26.9%) genotypes. These results showed that CC genotype was associated with SVR. Conclusions: It can be concluded that the individuals with IL28B TT genotype are more susceptible to HCV infection in Egyptian patients and relapse. Moreover, IL-28B CC is useful for pretreatment prediction of the outcome of HCV treatment. Hence, IL28B polymorphism could be considered as a pharmacogenetic predictor in personalized HCV therapy and pharmacogenomics during SOF plus PEG-IFN and RBV therapy for chronic hepatitis C Egyptian patients.