IL28B Genotype 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.

Interleukin-1 Beta rs16944 and rs1143634 and Interleukin-6 Receptor rs12083537 Single Nucleotide Polymorphisms as Potential Predictors of COVID-19 Severity.

Host genetic variation has been recognized as a key predictor of diverse clinical sequelae among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. Insights into the link between the Interleukin-6 receptor (IL-6R) and Interleukin-1 beta (IL-1β) genetic variation and severe coronavirus disease 2019 (COVID-19) are crucial for developing new predictors and therapeutic targets. We aimed to investigate the association of IL-6R rs12083537, IL-1β rs16944, and IL-1β rs1143634 SNPs with the severity of COVID-19. Our study was conducted on 300 COVID-19-negative individuals (control group) and 299 COVID-19-positive cases, classified into mild, moderate, and severe subgroups. Analyses of IL-1β (rs16944, rs1143634) and IL-6R (rs12083537) SNPs' genotypes were performed using qPCR genotyping assays. The IL-1β (rs16944) CC genotype and IL-6R (rs12083537) GG genotype were substantially related to COVID-19 severity, which was also associated with comorbidities and some laboratory parameters (p < 0.001). The IL-1β (rs1143634) TT genotype was found to be protective. Likewise, the IL-1β (rs16944) CC genotype was associated with increased mortality. IL-1β rs16944 and IL-6R rs12083537 SNPs are promising potential predictors of SARS-CoV-2 disease severity. Meanwhile, the rs1143634 SNP T allele was protective against severity and mortality risk.

Association of TNFα and IL1β genotypes with the risk of Staphylococcus aureus causing recurrent tonsillitis in a sample of Iraqi patients

Background and aim: Tonsillitis is an inflammation of the tonsils, usually caused by an infection by viruses or bacteria; recurrent tonsillitis occurs when tonsillitis occurs several times a year. The current study aimed to investigate the association of TNFα and IL1β genotypes with the increased risk of recurrent Staphylococcus aureus tonsillitis in a sample of Iraqi patients. Methods: A total of 50 blood samples were collected from patients with recurrent tonsillitis of S. auerus from three hospitals in Najaf city, and 50 samples were collected from apparently healthy volunteers with a free medical history of recurrent tonsillitis as control group. Genomic DNA was extracted from peripheral blood and genotyped for TNF-α 308G/A and IL1β C/T SNP using Nested tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Results: The results of the distribution IL β –rs1143627 C/T alleles in S. aureus tonsillitis patients showed CC wild type genotype was in 11 patients (22%), CT genotype was in 30 patients (60%) and the TT genotype was in 9 patients (18 %) also C allele frequency was (0.42), whilst T allele frequency was (0.58) with Odds Ratio (1.507) at significant difference (P≤ 0.01), while prevalent of TNF-α –rs1800629 G/A alleles genotype in S. aureus tonsillitis patients revealed that GG wild type genotype was 37 patients (74%), GA genotype was 13 patients (26%) and AA genotype was 0(0%) also, G allele frequency was (0.87) and A allele frequency was (0.13) with Odds Ratio (1.507) at no significant differences in both the patient and control.

Evaluation of the Association between Genetic Polymorphism of Interleukin-1 Beta (–511C/T and +3953C/T) and Cervical Cancer Susceptibility

Cervical cancer (CC) is the leading cause of cancer-related mortality among women, primarily caused by persistent human papillomavirus (HPV) infection, especially in developing countries. A proinflammatory cytokine, emerging as a major facilitator of carcinogenesis, is termed interleukin-1 beta (IL-1β), which characterizes host-environment interactions. Numerous epidemiological studies have revealed that IL-1β gene polymorphisms have been associated with numerous malignancies, but in the context of CC, results of these studies were inconclusive. Thus, our study aimed to explore the relationship between IL-1β polymorphisms (-511C/T and +3953C/T) and CC susceptibility. Genotyping was conducted on 192 CC patients and 200 healthy controls through polymerase chain reaction-restricted fragment length polymorphism. HPV analysis was done through real-time polymerase chain reaction, and the serum concentration of IL-1β was measured by enzyme-linked immunosorbent assay. Women with CT and TT genotypes of IL-1β -511C/T had a threefold increased risk of CC (odds ratio [OR], 3.60; 95% confidence interval [CI], 2.132-6.063; p &lt; 0.001 vs. OR, 3.34; 95% CI, 1.952-5.713; p &lt; 0.001) compared to controls. Women with the T allele of IL-1β -511C/T polymorphism were associated with increased CC susceptibility (OR, 2.00; 95% CI, 1.51-2.66; p = 0.0001) compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL-1β +3953C/T polymorphism (OR, 0.93; 95% CI, 0.56-1.55; p = 0.86 vs. OR, 0.95; 95% CI, 0.72-1.26; p = 0.74). There was no significant association found between IL-1β -511C/T promoter (OR, 2.41; 95% CI, 0.46-12.76; p = 0.28 vs. OR, 1.64; 95% CI, 0.13-21.10; p = 0.7) and +3953C/T (OR, 3.76; 95% CI, 0.44-31.82; p = 0.19 vs. OR, 0.21; 95% CI, 0.01-3.92; p = 0.25) polymorphisms in tobacco chewers and smokers compared to controls. The level of serum concentration of IL-1β was significantly higher in cases compared to controls. Our results conclude that IL-1β -511C/T polymorphism is associated with CC susceptibility.

Polymorphism of proinflammatory inerleukin genes in primary open-angle glaucoma

Glaucoma is a degenerative disease of the optic nerve, accompanied by the death of retinal ganglion cells (RGCs) and loss of vision. An important role in the pathogenesis of glaucoma is ascribed to activated microglia, which produce pro-inflammatory interleukins and initiate GCS apoptosis. It has been established that single nucleotide polymorphisms of interleukin genes modify the development of neuroinflammation, but their effect on the risk of developing glaucoma is not yet fully established. Our aim was to determine the pathogenetic role of gene polymorphisms in TNFα and IL1β in the development of primary open-angle glaucoma.We have observed 56 patients of Russian nationality from the South of Russia with primary open-angle glaucoma (POAG), 28 patients with stage I, 16 with stage II, 12 with stage III POAG. The single nucleotide polymorphisms TNFα 308G&gt;A (rs1800629) and IL1β -31 Т&gt;С (rs1143627) were studied by restriction fragment analysis of PCR products. The level of pro-inflammatory cytokines (TNFα and IL1β) in the lacrimal fluid of patients with POAG was evaluated by enzyme-linked immunosorbent assay (Vector-Best test system). To perform optical coherence tomography by analysing the thickness of retinal nerve fiber layer (RNFL) with volume and area of the neuroretinal rim using Torson 3D OST 1000 apparatus.Results: in patients with POAG, we have found more common incidence of TNFα 308A (OR = 5.21, p = 0.001), and IL1β-31 T alleles (OR = 1.99, p = 0.04). An increased risk of developing POAG was found in carriers of genotypes 308A/A (OR = 6.30, p = 0.049), 308G/A (OR = 3.60, p = 0.049) and -31T/T (OR = 2.67, p = 0.04). The highest levels of TNFα were determined in the 308A/A group (190 (153.0-220.0) pg/mL), IL1β were in the group (-31) T/T – 6.50 (4.10-7.00) pg/mL. A decreased thickness of the retinal nerve fibers was observed in the patients with TNFα G308A genotype (59.5; 40.0 to 78.0 µm, p = 0.03), and in TNFα A308A carriers (79.0; 65.0 to 80.0 µm, p = 0.001).The TNFα 308 G/A (rs1800629), along with IL1β, -31Т/C (rs1143627) cytokine gene polymorphisms are associated with development of primary open-angle glaucoma. TNFα 308A, IL1β -31T alleles, as well as the 308G/A, 308A/A and -31T/T genotypes seem to be the risk factors for POAG in Russian population. High content of TNFα in the lacrimal fluid was found in the carriers of 308A/A genotype and -31T/T IL1β genotype. The lowest thickness of the retinal nerve fiber layer was observed in the carriers of tTNFα A308A and TNFα G308A genotypes.

Cytokine polymorphisms and genotypic susceptibility of HCV infection in ribavirin response to peg interferon.

Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.

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.

Influence of IL-28B serum level and gene polymorphism in a sample of Iraqi patients with ankylosing spondylitis

Ankylosing spondylitis (AS) represents one kind of advanced arthritis formed via inflammatory stimuli long-term in the spin‘s joints. Interleukin (IL)-29 (interferon- lambda1(IFN- λ1)), interleukin (IL)-28A (interferon- lambda 2 (IFN- λ2)) and interleukin (IL)-28B (interferon- lambda 3(IFN-λ3)) are three interferon lambda (IFN- λs) molecules that have recently been identified as new members of the IFN family. IL-28B expression in ankylosing spondylitis (AS) is not well understood. 150 male healthy controls ((HC) and 160 males with AS as patients group participated in this study. Serum level and gene polymorphism were assessed using an enzyme-linked immunosorbent assay and Sanger sequencing for IL-28B, respectively. The results showed significantly lower serum IL-28B concentrations in the AS groups in comparison to the HC groups (both p values equal to 0.003). There was a large difference in IL-28B genotype and allele frequency between the two individuals. IL-28B heterozygote genotype CT of rs12979860 SNP exhibits a substantial correlation with AS (P = 0.008). While the genotypes of rs12980275 SNP were not shown any significant correlation with AS. The findings suggest that serum concentration of IL-28B is a potential diagnostic biomarker in patients with AS, and that the heterozygote CT of rs12979860 SNP serves as a potential risk factor for the onset of AS in the Iraqi population.

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.

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Objective We investigated the relationships between interleukin- (IL-) 1β and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN). Methods The genotype and allele frequency distribution of IL-1β and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1β and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA). Results Significant differences were detected in the distribution of IL-1β (−511C/T) genotype and allele frequencies between the DN and HC groups (P < 0.05), with the T genotype being more frequent in DN patients than HCs (OR = 2.84, 95% CI: 1.489–5.416). The IL-1β (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups (P > 0.05). The plasma IL-1β level was significantly higher (P < 0.01), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group (P < 0.05). Furthermore, the plasma IL-1β level was significantly different between IL-1β (−511C/T) locus variants (P < 0.05). Conclusion The IL-1β (−511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

Pro-inflammatory and anti-inflamatory cytokine genes polymorphisms and susceptibility to Japanese encephalitis disease in the North Indian population.

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in many regions of Asia. Cytokines, including pro-inflammatory and anti-inflammatory are key regulators playing a detrimental role in the host response to JE infection, pathogenesis and disease outcome. Evidently, the host's cytokine response is genetically determined, representing the complexity of interindividual differences regarding immune response to viral infection. The current study assesses the association of single nucleotide polymorphisms of classical interleukin IL-1β and IL-10 with JEV susceptibility and disease severity in north Indian population. We performed a case-control study using 85 JE patients and 85 healthy controls. Polymorphisms in the IL-1β (-511 C/T) and IL-10 (-1082 A/G) genes were genotyped using PCR-RFLP. All continuous variables were expressed as mean±standard deviation, and categorical variables were expressed in percentage. The mRNA level of IL-1β and IL-10 were found significantly increased in JE patients. In severe JE patients, IL-1β mRNA level was significantly higher with heterozygous (C/T) and homozygous (C/C) genotype compared to wild (T/T) genotype and mRNA level of IL-10 was higher in heterozygous genotype (A/G) compared to wild genotype (A/A). The C/T and C/C genotypes of IL-1β were significantly associated with higher risk of JE infection (p<0.05, OR=7.25 and 4.40) whereas, the A/G genotype of IL-10 was associated with a reduced risk of JEV infection (p<0.05, OR=0.30). The C allele of IL-1β was associated with fever and neck stiffness (p<0.05) and CT genotype was associated with disease severity and worse outcomes in JE patients. Along with this, IL-10 polymorphism was found associated with fever, and AG genotype was found to be associated with worse disease outcomes such as neurological sequelae (p<0.05). Mutant allele and genotype at IL-1β (-511 C/T) and IL-10 (-1082 A/G) gene polymorphism show increased expression of IL-1β and IL-10 in JE patients which contribute to disease severity as well as adverse outcomes of disease. Overall this is the first report from northern India, which shows the association of IL-1β and IL-10 polymorphisms with JEV infection.

The impact of single-nucleotide polymorphisms on liver stiffness and controlled attenuation parameter in patients treated with direct-acting antiviral drugs for hepatitis C infection.

Single-nucleotide polymorphisms (SNPs) of patatin-like phospholipase domain-containing 3 (PNPLA3), tolloid-like protein 1 (TLL1) and interleukin-28 (IL28) have been identified as susceptibility factors for liver steatosis, inflammation and fibrosis in patients with hepatitis C virus (HCV) infection. Here, whether these polymorphisms affected predispositions to changes in liver stiffness (LS) and controlled attenuation parameter (CAP) following direct-acting antiviral (DAA) therapy was assessed. The changes in LS and steatosis in 77 HCV-infected patients receiving DAA therapy were compared with PNPLA3, TLL1 and IL28 genotypes, using CAP, FibroScan and Virtual Touch tissue quantification (VTTQ) before treatment and 12 weeks after the end of the treatment. VTTQ results showed that LS significantly decreased in PNPLA3 CC (P=0.035), TLL1 AA (P=0.011) and IL28B TT (P=0.005) genotypes; no significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG. FibroScan results showed that LS significantly decreased in TLL1 AA (P=0.028) and IL28B TT (P=0.032), with no significant difference in PNPLA3 CC. No significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG groups. CAP was significantly increased in PNPLA3 CG/GG (P=0.039 and P<0.05) and IL28B TT (P=0.014); no significant difference was observed in PNPLA3 CC and all genotypes of TLL1 and IL28B TG/GG. Therefore, these results indicated that SNPs could predict changes in LS and steatosis after DAA therapy.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Assessment of New E2 Protein Domain Interaction with PKR Protein to Control IFN Signaling

Introduction: Controversy exists regarding the impact of Phosphorylation Homology Domain (PePHD) of Hepatitis C Virus (HCV) E2 protein on the interruption of the antiviral signaling pathway. A mechanism by which the virus evades the antiviral effect of interferon (IFN) alpha involves protein kinase (PKR) eukaryotic Initiation Factor 2 alpha (eIF2a) PePHD. By binding to PKR, PePHD inhibits its activity and, therefore, causes the virus to evade the antiviral activity of IFN. This study aimed to clarify the inconsistency of different conclusions reached in previous studies using reliable bioinformatics tools. Methods: Fifty-eight Iranian patients infected with HCV genotypes 1a and 3a and 58 healthy control individuals were examined. Plasma viral RNA was used to amplify and sequence the HCV E2 gene; also, HCV viral load, genotyping, IL-28B genotyping, alanine Aminotransferase (ALT), and aspartate aminotransferase (AST) test were determined. Bioinformatics tools determined the physicochemical properties, B-cell epitopes, post-modification changes, and secondary/tertiary structures, and also evaluated the interactions between E2 and PePHD regions. Results: The results showed a new domain that is responsible for binding to PKR protein and is important to the intrigued antiviral response. Physicochemical features and post-modifications were defined, showing that E2 is highly phosphorylated and there were numerous possible disulfide bonds. Secondary and tertiary structures for E2 protein were constructed. No significant relationship between ALT and AST and treatment failure was detected. Conclusions: Docking analysis showed a new domain in E2 protein that can be involved in the interaction between PKR and E2 protein. This finding may justify our results revealing the non-significant relationship between mutations in PePHD and treatment failure.

Recipient IL28B genotype CT is a predictor of new onset diabetes mellitus in liver transplant patients with chronic hepatitis C

Recipient IL28B genotype CT is a predictor of new onset diabetes mellitus in liver transplant patients with chronic hepatitis C

Association between common polymorphisms in IL-1 and TNFα and risk of peri-implant disease: A meta-analysis.

BackgroundPro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) play important roles in host immune response and bone metabolism during dental implant osseointegration. Whether the functional polymorphisms in IL-1α, IL-1β and TNFα were associated with peri-implant disease was unclear, and we performed the present meta-analysis for this purpose.MethodsEligible studies investigating IL-1α C-889T, IL-1β C+3954T and C-511T, TNFα G-308A, composite genotype of IL-1α C-889T and IL-1β C+3954T for association with peri-implant disease, including peri-implantitis (PI), marginal bone loss (MBL) and implant failure/loss (IF/IL), were searched on several literature databases prior to April 30, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for each polymorphism in different genetic models and for composite genotype comparing carriers to non-carriers.ResultsTwenty-seven studies (1324 cases with peri-implant disease and 1808 controls with healthy implants) were included. There was significant correlation between IL-1α C-889T and peri-implant disease in all genetic models. IL-1β C+3954T was associated with peri-implant disease risk in allelic (OR = 1.66, 95%CI 1.17–2.35, p = 0.004) and dominant model (OR = 1.74, 95%CI 1.19–2.53, p = 0.004), and in subgroups of Asians, Caucasians, non-smokers, IF/IL and PI. TT genotype of IL-1β C-511T increased the risk of peri-implant disease (OR = 1.68, 95%CI 1.15–2.43, p = 0.007) and MBL (OR = 4.33, 95%CI 1.72–10.9, p = 0.002) compared to CC+CT genotypes. We did not observed a significant association between TNFα G-308A and peri-implant diseases in overall or subgroups analysis. Carriers of positive composite genotype of IL-1α C-889T and IL-1β C+3954T had 1.95-fold (95%CI 1.35–2.80, p<0.001) risk of peri-implant disease and 1.76-fold (95%CI 1.05–2.95, p = 0.032) risk of IF/IL than non-carriers.ConclusionFunctional polymorphisms of IL-1α (C-889T), IL-1β (C+3954T, C-511T) and composite genotype of IL-1 can be used as predictive markers for peri-implant disease, whereas TNFα G-308A polymorphism was not associated with peri-implant disease.

Impact of IL28B Polymorphism on the Response to Treatment of Hepatitis C with Interferon Based Therapy or Direct Acting Antivirals

Abstract Background: A major impact of the IL28B gene polymor-phism on the response to antiviral therapy in chronic hepatitis C have been described recently by a lot of studies. This study aims to scrutinize the impact of IL28B genotypes of donors and recipients on the response to treatment with INF based therapy or DAA among patients that underwent liver trans-plantation. Aim of Study: This study aims to correlate IL28B genotype of donors and recipients for patients that had undergone liver transplantation with the response to INF based therapy, and the response to Direct Acting Antivirals (DAA). Patients and Methods: Donor and recipient IL28B geno-typing by PCR was done for 24 patients who experienced LT for HCV-induced end stage liver disease with established standard follow up evaluations post liver transplant for two years. Pegylated interferon-a (PEG-IFN-a) and ribavirin were received by 10 of the patients and direct acting antiviral (DAA) agents were offered to the remaining 14 patients. Results: We found that there was no impact of IL 28B polymorphism on the response to anti viral treatment (AVT) by (DAA) agents, as all different IL 28B genotypes and different recipient/donor patterns eventually achieved SVR even in cases with two unfavorable non-CC genotypes in both recipients and donors. We also found that the donor rs 12979860 CC genotype was strongly associated with the success of PEG-IFN-a and ribavirin treatment of recurrent hepatitis C. Conclusions: In the era of DAAs, it seems likely that it will be possible to overcome the effect of IL28B polymorphism with DAAs combinations.

Influence of IL28B of Donors and Recipients on Liver Transplantation Due to End Stage HCV Related Liver Disease

Abstract Background: Recent studies have described a major impact of the IL28B gene polymorphism on graft survival post liver transplantation. Our study aims to investigate the impact of IL28B of donors and recipients on the natural course and outcome of liver transplantation due to end stage HCV related liver disease. Aim of Study: This study aims to investigate SNP of IL28B gene in Egyptian patients with end stage HCV related liver disease. Correlating the prevalence of IL-28b-alleles with patient and graft survival and with the progression of fibrosis for HCV-induced (graft) liver disease after liver transplantation. Also to correlate IL28B genotype with the outcome after liver transplantation. Patients and Methods: Donor and recipient IL28B rs12979860C>T single nucleotide genotype was determined in 24 patients who had undergone LT for HCV-induced end stage liver disease and received regular follow-up evaluations for two years post liver transplantation. Results: We found that the CC genotype frequency was reduced among patients with HCV related end stage liver disease while, in contrast, the frequency of CT & TT increased. No association was noted between IL 28B polymorphism of donors and recipients regarding fibrosis progression or patient and graft survival, as well as liver outcomes. Conclusions: No impact of IL 28B polymorphism on fibrosis progression, liver outcomes or patient and graft survival.

IL28B, TLR7 SNPs, and cytomegalovirus infection are risk factors for advanced liver disease in chronic hepatitis C patients

ABSTRACT BACKGROUND Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). This study aimed to study association of IL28B, toll like receptor (TLR) 7, cytomegalovirus and advanced liver disease. METHODS : Four groups were included; control (n=125, 25.9%), CHC (n=114, 23.6%), liver cirrhosis (n=120, 24.8%), and HCC (n=124, 25.7%). RESULTS In CHC group, patients were mainly F1 (60%) followed by F2. IL28B genotype CC percentage was higher in control group than the CHC and cirrhosis groups. CT and TT genotypes were higher in the CHC and cirrhosis groups than control group. The C allele was higher in the control group than the CHC, cirrhosis and HCC groups and the opposite with the T allele. Control and CHC had same TLR7 alleles. Cirrhosis patients and HCC had lower TLR 7 A allele and higher G allele than the control group. Both cirrhosis and HCC groups had statistically significant higher percentage of the AG and GG genotypes than the control group. Patients with HCC had higher cytomegalovirus infection percentage than cirrhosis and CHC group (38.7% vs 20% vs 16.7%) respectively. CONCLUSION IL28B, TLR7 SNPs and cytomegalovirus infection are risk factors for advanced liver disease in hepatitis C patients.

Сatamnestic data on the effect of interferon therapy on the course of combined HIV/HCV-infection

Aim: catamnestic analysis of the effectiveness of antiviral therapy for chronic hepatitis C in combination with HIV infection.Materials and methods. A retrospective study included 145 patients with combined HCV/HIV infection for 8±0,43 years.Results. 55% of patients received antiviral therapy for chronic hepatitis with pegylated interferons and ribavirin. The frequency of achieving a stable virological response is 73%. Persistent virological response with favorable Il-28B genotypes was detected in 85% of cases, with unfavorable genotypes less frequently — in 63% (p=0,028); the relapse rate is 27%. The level of HIV RNA viral load and the frequency of patients with secondary diseases was higher in patients with natural HCV/HIV infection with favorable interleukin-28B genotypes compared to other comparison groups (р&lt;0,05).Conclusion. The course of chronic hepatitis C after therapy was more positive with favorable Il-28B genotypes. HIV infection was more severe in the absence of antiviral therapy for chronic hepatitis C.