IL28B Rs12979860 Research Articles

Elevated serum levels of adiponectin and interlukin-28B after IFN/RIB therapy in hepatitis C virus-infected patients.

The interleukin 28B (IL28B) genotype is associated with changes of lipid metabolism in patients infected with hepatitis C virus (HCV). The association of steatosis with serum levels of adiponectin in chronic hepatitis C (CHC) patients has also been documented. This study aimed for the evaluation of serum levels of IL28B and adiponectin as well as the association of IL28B SNPs with different clinicopathological parameters in HCV-infected patients. All 142 HCV-infected patients received peg-interferon plus ribavirin. Detection of rs8099917 and rs12979860 IL-28B genotypes was done with specific primers. Serum IL28 and adiponectin levels were measured using commercial ELISA kits. Higher levels of both IL28 and adiponectin were found in patients. In Genotype 3a (G3a) -infected patients, IL28 and adiponectin serum levels were significantly higher than those infected with G1a. A correlation was found between increasing levels of AST and ALT in G3a-infected patients and the decrease in IL28 and adiponectin serum levels, respectively, in contrast to G1a-infected patients. Higher levels of both IL28 and adiponectin were associated with both CT allele of rs12979860 and TT allele of rs8099917 in patients in comparison with corresponding alleles in controls. In contrast to other studies, this study showed higher serum adiponectin levels in HCV-infected patients compared to that in healthy controls. This finding is possibly due to adiponectin resistance caused by down-regulation of adiponectin receptors or tumorigenic effects of adiponectin. Our genotype-based analyses revealed, at least in part, the involvement of the viral factors in the outcome of HCV infection.

Correlation between IL28B/TLR4 genetic variants and HCC development with/without DAAs treatment in chronic HCV patients

In Egypt, Sofosbuvir (SOF) in combination with Dataclasvir (DCV) is the broadly used DAAs with excellent therapeutic profile. This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of the followings; HCC development post SOF/DCV treatment, progression to HCC in naïve patients and SOF/DCV therapy outcome. A total of 493 blood samples were collected (controls (n = 70); HCV patients treated with SOF/DCV (n = 252) of whom 65 patients developed HCC, 187 patients didn't develop HCC (125 responders, 62 relapsers); naïve HCV patients (n = 171) had early (n = 48), late liver fibrosis (n = 21) and HCC (n = 102)). Both SNPs were genotyped using a TaqMan 5′ allelic discrimination assay. At IL28B rs12979860 SNP, the C allele was significantly correlating with the response rate more than T allele (OR 1.9, 95% CI 1.29–2.9, p = 0.004), while at TLR4 rs4986791 SNP, no association was found (OR 6.5, 95% 0.57–75.28, p = 0.09). Both SNPs couldn't detect the probability for HCC emergence after treatment. In naïve patients, the protective alleles were detected in their lowest frequency in HCC patients (p = 0.1, for rs12979860 and, p = 0.001 for rs4986791). SOF/DCV combination improved SVR rates in HCV genotype 4a infected patients regardless of IL28B genotype, with the best rates in those lacking the T allele.

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.

Association of IL28B (IFNL3) rs12979860 mRNA levels, viral load, and liver function among HCV genotype 1a patients.

The present study was designed to evaluate the correlation of interleukin 28B (IL28B, IFNL3) rs12979860 mRNA levels, viral load, and liver function among hepatitis C virus (HCV) patients genotype 1a. HCV is considered essentially hepatotropic and is a major health problem around the world. This study included 100 HCV-infected patients with HCV genotype1a (G1a) and rs12979860 CC genotype. These patients were divided into two groups according to HCV treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and HCV Load were measured and recorded for each patient. IL28B mRNA levels were determined using real-time polymerase chain reaction assay, and their correlation with clinical data were analyzed. STRING was applied to construct a network and identify interactions between IL28B (IFNL3) and its significant neighbor proteins. The results revealed a significant relationship between the ALT as well as ALP levels with IL28B rs12979860 mRNA expression level in men, and also with age >50 years. In the treated group, AST level and HCV load had a significant relationship with IL28B mRNA expression level. The results showed that the level of ALP and AST decreased significantly with increased IL28B mRNA expression level in the treated and untreated group, respectively. STRING database showed that IL28B (IFNL3) interacted with ten important neighbor proteins with some of these proteins being involved in signal transduction pathway activating antiviral response. This study indicated that rs12979860CC genotype could predict IL28B mRNA expression level in HCV-infected patients with G1a. Furthermore, IL28B mRNA expression level may serve as a useful marker for the development of G1a HCV-associated outcomes.

The interleukin 28B gene polymorphism, rs8099917, in patients with chronic hepatitis C and response to the treatment with pegylated interferon and ribavirin.

Background:The present study aimed to determine the frequency of the IL28B polymorphism rs8099917 in patients with genotype 1 hepatitis C virus (HCV) infection treated with pegylated-interferon-α2b (PEG-IFN-α2b) and ribavirin (RBV) and its treatment outcome.Materials and Methods:The IL28B rs8099917 genotypes were determined among 100 HCV-infected patients and the viral load was also estimated. PEG-IFN-α2b and RBV combination were administrated to the patients for 48 weeks and the treatment outcome was defined.Results:Sixty-seven (67%), 27 (27%), and 6 (6%) of 100 patients were determined as TT, GT, and GG genotype, respectively. The response rate to treatment was significantly higher in patients with TT genotype.Conclusion:According to the results of the present study, patients with IL28B rs8099917 TT genotype achieve higher sustained virological response than the GT and GG genotypes. Thus, when there are no alternatives, treatment with PEG-IFN-α2b and RBV combination can be suggested in patients with IL28B TT genotype.

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.

Correlation of IL28Brs12979860 genotype and gender with spontaneous clearance of HCV infection: a Pakistani cross-section study.

There is a strong correlation of IL28B rs12979860 genetic variations and gender with spontaneous clearance of hepatitis C virus (HCV) infection. HCV-infected subjects were categorized into HCV spontaneous clearance (SC) group and chronic hepatitis C (CHC) group on the basis of anti-HCV antibodies and HCV RNA level and follow-up of 6 months. 35 subjects were classified in SC group and 165 subjects were classified in CHC group. IL28B rs12979860 genotypes were determined by allele-specific PCR. Multinominal logistic regression analyses revealed that both genders favor IL28B rs12979860 CT genotype (OR: 4.80; CI: 2.22-10.35; p =0.0005) and (OR: 3.47; CI: 1.63-7.43; p =0.001) for male and female, respectively, are significant in spontaneous clearance of HCV infection.

Predictive value of IL-28B rs12979860 variants for peg-IFN, sofosbuvir plus ribavirin treatment of HCV infection in Pakistani population.

The correlation of IL28-B genetic variants (rs12979860) with combinational therapy (peg-interferon, sofosbuvir plus ribavirin) of hepatitis C virus infection were studied in 154 chronic hepatitis C patients. The sustained virological response for efficient antiviral regimen was achieved in 75.32% treated individuals. Three genotypes of rs12979860 (CC, CT and TT) were compared both in sustained virological response and nonresponders groups (p=0.25, p≤ 0.001, p=0.10, respectively). CT genotype demonstrated a significant correlation (p≤ 0.001) in both groups with higher positive predictive value (81.55%). IL28 polymorphism and positive predictive value may be considered as the markers for the evaluation of the effectiveness of the treatment regimen. Further clinical trials are recommended to verify the role of IL28-B in hepatitis C virus treatment.

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.

Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.

Efficacy of ledipasvir/sofosbuvir with or without ribavirin for 12 weeks in genotype 1b HCV patients previously treated with a nonstructural protein 5A inhibitor-containing regimen.

The therapeutic benefit of adding ribavirin (RBV) to 12weeks of ledipasvir/sofosbuvir (LDV/SOF) for patients who experienced failure of a previous nonstructural protein (NS) 5A inhibitor-containing regimen is unclear. A total of 29 genotype 1b HCV patients who had failed prior daclatasvir (DCV) plus asunaprevir (ASV) treatment were retreated for 12weeks of LDV/SOF, with or without RBV. Antiviral efficacy and predictive factors associating with a sustained virological response at 24weeks (SVR24) were evaluated retrospectively. SVR24 was achieved in 67% (10/15) of patients who received LDV/SOF with, and 64% (9/14) without, RBV. The SVR24 rates were 80% in patients with, and 58% without, mild fibrosis (FIB-4 < 3.25). The SVR24 rate was lower with unfavorable IL28B rs8099917 SNP genotypes; specifically, the TT, TG and GG had SVR24 rates of 78%, 50% and 40%. The SVR24 rate was lower with a poor response to prior DCV plus ASV, where relapse, viral breakthrough and no response had SVR24 rates 71%, 58% and 0%. The SVR24 rate was lower with the number of NS5A resistance-associated substitutions (RAS), where 2, 3, 4 and 5 RAS had SVR24 rates of 78%, 67%, 50% and 0%. A patient with an NS5A-P32 deletion, which shows resistance to next-generation NS5A inhibitors, was retreated with LDV/SOF with RBV and achieved SVR24. The addition of RBV to 12weeks of LDV/SOF has little therapeutic benefit when retreating patients in whom a prior NS5A inhibitor-containing regimen had failed.

Lack of evidence of association between IFNG and IL28B polymorphisms and QuantiFERON-CMV test results in seropositive transplant patients

The aim of this study was to analyze the relationship between the IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms and the secretion of IFNG by CD8+ T cells after stimulation with cytomegalovirus (CMV) peptides, measured using QuantiFERON-CMV (QF-CMV) assay. A total of 184 CMV-seropositive solid organ transplant patients (108 kidney, 68 liver and 8 lung) were recruited. Of them, 151 patients were QF-CMV Reactive (IFNG ≥ 0.2 UI/mL) and 33 were Non-reactive. Genotype frequencies in the study population were TT (26.6%), AT (50.0%) and AA (23.4%) for IFNG +874 and CC (52.7%), CT (39.1%) and TT (8.2%) for IL28B (rs12979860). These frequencies did not significantly differ between QF-CMV Reactive and Non-reactive patients. Nor were any significant differences observed in the quantitative IFNG level among the genotypes in either the IFNG or the IL28 genes. When we analyzed whether these polymorphisms had any impact on the risk of CMV replication after transplantation, the adjusted analysis showed no association. In summary, our results showed that IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms are not associated with the IFNG response to CMV measured by the QuantiFERON-CMV assay, although these results should be confirmed with a higher number of patients.

Genetic variation in IL28B (IFNL3) and response to interferon-alpha treatment in myeloproliferative neoplasms.

In myeloproliferative neoplasms (MPN), interferon-alpha (IFN-α) is an effective treatment with disease-modifying properties but currently with no clear predictors of treatment outcome. Recent genomewide association studies in chronic hepatitis C have found a strong influence of genetic polymorphism near the IL28B (IFNL3) gene in response to IFN-α treatment. In this study, we sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and rs12980275 on IFN-α treatment response in myeloproliferative neoplasms. We retrospectively evaluated 100 patients with MPN treated with IFN-α. The hematologic treatment response on IFN-α was compared between patients and correlated with host genetic variations in IL28B. The genotypes of IL28B were determined by allelic discrimination assays. The CC genotype of rs12979860 was found significantly associated with hematologic response in polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48% (non-CC), (P=.036). No association between the genotypes and treatment response on hydroxyurea was found. These results imply an effect of IL28B genotype on the outcome of IFN-α treatment in MPN.

Interleukin gene polymorphisms and susceptibility to HIV-1 infection: a meta-analysis

Some subjects are repeatedly exposed to human immunodeficiency virus (HIV), yet they remain uninfected. This suggests the existence of host-resistance mechanisms. The current study synthesizes the evidence regarding the association between interleukin (IL) gene polymorphisms and HIV susceptibility. Medline, Scopus and the Web of Science databases were systematically searched, and a meta-analysis of case-control studies was conducted. Univariate and bivariate methods were used. The literature search identified 42 eligible studies involving 15,727 subjects. Evidence was obtained on eight single-nucleotide polymorphisms (SNPs): IL1A -889 C>T (rs1800587), IL1B +3953/4 C>T (rs1143634), IL4 -589/90 C>T (rs2243250), IL6 -174 G>C (rs1800795), IL10 -592 C>A (rs1800872), IL10-1082 A>G (rs1800896), IL12B -1188 A>C (rs3212227) and IL28B C>T (rs12979860). The IL1B +3953/4 C>T variant appears to increase the risk of HIV acquisition, under the assumption of a recessive genetic model (odds ratio (OR): 4.47, 95% CI: 2.35-8.52). The AA homozygotes of the IL10 -592 C>A SNP had an increased, marginally nonsignificant, risk (OR: 1.39, 95% CI: 0.97-2.01). It reached, however, significance in sub analyses (OR: 1.49, 95% CI: 1.04-2.12). Finally, the well-studied hepatitis C virus (HCV) infection IL28B (rs12979860) CT/TT genotypes were associated with a 27% decrease in HIV infection risk, especially in populations infected with HCV (OR: 0.73, 95% CI: 0.57-0.95). Interleukin signalling is perhaps important in HIV infection and some interleukin genetic variants may affect the risk of HIV acquisition. Approaches targeting specific genes and genome wide association studies should be conducted to decipher the effect of these polymorphisms.

Association of IL-28B, TBX21 gene polymorphisms and predictors of virological response for chronic hepatitis C.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. The outcomes of both spontaneous HCV clearance and response to therapy depend on both viral and host factors. To investigate the influence of polymorphisms of IL-28B rs12979860 and TBX21 rs17250932, rs4794067 as well as viral factors (HCV genotype, F protein) on the outcome of HCV infection, we genotyped 565 patients with chronic HCV infection, 191 patients spontaneously resolved from HCV infection, 359 healthy controls and 383 treatment-naïve CHC patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV). Results showed that TBX21 rs4794067 variant genotypes significantly correlated with increased risk of HCV chronic infection (dominant model: OR=5.690, 95% CI=2.024-16.000) and susceptibility (dominant model: OR=5.658, 95% CI=2.514-12.735). We also found that the rs12979860, rs2227982 and rs36084323 polymorphisms showed no significant associations with susceptibility or spontaneous clearance of HCV in the anti-F antibody subgroup; however, the anti-F antibody positive subgroup might show an increased risk of N-SVR (all P<0.001). Our results demonstrate that variant factors in both the host and pathogen are commonly important for HCV clearance. In addition rs4794067 and F protein status may be strong predictive markers in the Chinese population.

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.

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

Background: Hepatitis C virus (HCV) is a major cause of chronic liver disease, including cirrhosis and liver cancer. The aim of our study was to determine whether IL28B single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 can be considered a prognostic host factor in untreated chronic HCV patients. Methods: We set up a real-time Allele Specific PCR amplification to determine the allele present in each polymorphic site, and statistically grouped and compared this result with clinical data. Results: We determined rs12979860 and rs8099917 genotype and allele frequencies in a single cohort of untreated chronically HCV-infected patients. We found significant associations between higher inflammatory activity, measured as ALT levels or METAVIR scores and rs12979860 CC (P = 0.0013 and P = 0.0033, respectively) and rs8099917 TT (P = 0.0005 and P = 0.0264, respectively) genotypes. Interestingly, considering both genotypes together, we also found association with ALT levels (P = 0.0003; OR = 5.125) or METAVIR scores (P = 0.0038; OR = 5.179), suggesting and additive effect on liver inflammation in these patients. Conclusion: we show association between hepatic inflammatory activity in a single Argentinean untreated chronically HCV cohort and SNPs located in the interferon lambda gene region. The studied polymorphisms, together with further innate and adaptive immune responses, clearly play a role in modulating the HCV infected patients outcome, contributing to hepatic inflammation and possible fibrosis/cirrhosis.

IL28B is An Irrelevant Prognostic Factor for HCV in the Era of Highly Effective DAAs

Direct-acting antivirals (DAAs) therapies have ushered in the beginning of new era for HCV treatment. Comparative studies to understand the efficacy, safety and factors associated with treatment non-response to DAAs therapies are much-needed. The present study was conducted primarily to evaluate the efficacy and safety of sofosbuvir based DDAs therapy and secondly to investigate the role of host and viral factors especially rs12979860 with treatment response. This study showed that sofosbuvir based therapy was safe and associated with high rates of sustained virological response in both treatment naive and experienced patients. IL28B rs12979860 was not associated with sofosbuvir based treatment hence an irrelevant prognostic factor in our population.

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.