Interleukin 28B Rs12979860 Genotype Research Articles

Effect of Interleukin 28B SNP rs12979860 Genotype on Viral Load in Hepatitis C Virus in Kolar Population, Karnataka, India

Introduction: The natural course of Hepatitis C Virus (HCV) infection is influenced by a number of host and viral variables. Interleukin 28B (IL28B) is a kind of interleukin. A Single Nucleotide Polymorphism (SNP) designated as rs12979860 was reported to predict viral clearance with and without treatment. Subjects with the GG (favourable) IL28B rs12979860 genotype were more likely to clear the infection spontaneously and respond well to therapy. These findings imply that people who have the “favourable” GG genotype have a lower viral burden than those who have the “unfavourable” AA genotype. Aim: To determine the effect of IL28B SNP rs12979860 genotype on HCV viral load in Kolar population, Karnataka, India. Materials and Methods: The present study was a case-control study which was carried out in Department of Microbiology, Sri Devaraj Urs Medical College, Kolar, Karnataka, India. Subjects were enrolled from Department of Medicine of R. L. Jalapa Hospital and Research centre, teaching hospital of Sri Devaraj Urs Medical College between November 2020 to March 2021. A total of 248 were taken of which 124 were HCV antibody-positive and 124 were controls. The effect of IL28B rs12979860 SNP on HCV viral load and clearance among HCV-infected patients were examined. Detection and quantification of HCV-RNA was determined by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). IL28B rs12979860 genotyping was performed using PCR and Restriction Fragment Length Polymorphism (RFLP) technique and specific primers. Statistical analysis was done by using open epi tool. The frequency, percentage and Chi-square test were used to analyse categorical variable. A p-value <0.05 was considered as significant. Results: In this study the frequency of G/G genotype was considerably high 83 (67%) compared to G/A 17 (13.7%) and A/A 24 (19.3%) and in group 2 the frequency of G/G genotype 84 (67.7%), G/A genotype 34 (27.4%) and A/A genotype 6 (4.9%). There was a statistically significant difference in both the HCV infected and healthy controls groups (p=0.002). The average (±SEM) HCV viral load was 4.6±3.6×107 , 9.4±7.7×107 and 5.5±5.2×107 IU/mL in patients with the IL28B rs12979860 GG, GA and AA respectively. Also there was a significance between the viral load and IL28B rs 12979860 (p-value <0.05). Conclusion: Thus, present study results indicate that the IL28B rs12979860 genotype has an effect on viral load in untreated HCV patients. These findings highlight the importance of viralhost interactions in influencing the outcome of HCV infection.

Programmed cell death-1 rs11568821 and interleukin-28B rs12979860 polymorphisms in autoimmune hepatitis

BackgroundAutoimmune hepatitis (AIH) is a relatively rare chronic liver disease of unknown etiology. The genetic background affects susceptibility, clinical phenotype, and prognosis. The programmed cell death-1 rs11568821 polymorphism (PD1.3) has been associated with susceptibility to autoimmune diseases. The interleukin-28B (IL28B) rs12979860 polymorphism has been associated with steatosis, inflammation, and fibrosis in liver diseases. AimOur aim was to investigate for the first time the incidence and clinical significance of PD1.3 and IL28B rs12979860 in AIH. MethodsTwo hundred patients with AIH were evaluated, while 100 healthy subjects were used as controls. Genotyping was performed with in-house allelic discrimination End-Point PCR. ResultsThe SNP PD1.3/A was present in 36/200 (18%) AIH patients compared to 28/100 (28%) healthy controls (p = 0.065). The AA/GA genotypes were not associated with the mode of presentation of AIH, the histological grade or stage, the presence of cirrhosis, risk of disease progression, response to treatment and survival. The IL28B rs12979860 genotype distribution was CC 79/200 (39.5%), TT 36/200 (18%) and CT 85/200 (42.5%), in similar rates with healthy controls (p = 0.878). Inflammatory activity and fibrosis stage did not differ between CC homozygotes and CT/TT carriers. LDL cholesterol was significantly higher in CC than CT/TT patients (P = 0.027), though no differences was found regarding the presence of steatosis or steatohepatitis. On-treatment response to immunosuppressive treatment was not affected by the IL28B rs12979860 polymorphism. However, CC homozygotes AIH patients achieved treatment withdrawal in significantly higher rates (OR 2.3, 95%CI: 1.1–4.7, P = 0.02) irrespective of the presence of steatosis or steatohepatitis. ConclusionsThe PD1.3 and IL28B rs12979860 variants are unlikely to contribute to AIH susceptibility, disease presentation and prognosis. The IL28B rs12979860 is not associated with the presence of concurrent steatosis or steatohepatitis. However, although on-treatment response rates to immunosuppression were not affected by the IL28B rs12979860 polymorphism, AIH patients with CC homozygosity were more likely to achieve complete treatment withdrawal. This novel finding needs validation and further clarification from larger multicenter studies.

Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine–cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.

Role of IL-28B genetic variants in HCV-related liver disease severity in patients with different viral genotypes.

Reports of the role of host interleukin 28B (IL-28B) genetic variants in liver disease severity in patients with chronic hepatitis C (CHC) have obtained conflicting results. The impact of IL-28B in Asian patients with different viral genotypes remains elusive.We try to elucidate the effect of IL-28B genetic variants in a large Asian cohort with different viral genotypes.The association between the IL-28B rs8099917 genotype and liver fibrosis was investigated in 1288 patients with biopsy-proven CHC.Patients with hepatitis C virus genotype 1 (HCV-1) infection comprised 59.4% of the population. The remaining 40.6% (518 patients) did not have HCV-1 infection. Of the 1084 patients with the IL-28 genotype, 85.6% (928 patients) had the TT genotype. Univariate analysis revealed that, compared to patients without advanced liver fibrosis, patients with advanced liver fibrosis (Metavir fibrosis score 3-4) had an older age, a lower platelet count, a higher α-fetoprotein level, a higher alanine aminotransferase level, a higher incidence of diabetes, and a higher frequency of rs8099917 non-TT genotype carriage.Logistic regression analysis revealed that factors significantly associated with advanced liver fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 1.023/1.009-1.037, P = .001), diabetes (OR/CI: 1.736/1.187-2.539, P = .004), α-fetoprotein (OR/CI: 1.007/1.002-1.012, P = .009), platelet count (OR/CI: 0.991/0.988-0.993, P < .001), and carriage of the rs8099917 non-TT genotype (OR/CI: 0.585/0.400-0.856, P = .006). When patients were classified by viral genotype, factors that had significant independent associations with advanced liver fibrosis in patients with HCV-1 infection included diabetes (OR/CI: 2.379/1.452-3.896, P = .001), α-fetoprotein (OR/CI: 1.023/1.012-1.035, P < .001), platelet count (OR/CI: 0.99/0.987-0.994, P < .001), and carriage of the rs8099917 non-TT genotype (OR/CI: 0.529/0.328-0.854, P = .009). In patients who had advanced liver fibrosis but not HCV-1 infection, factors that had significant independent associations with advanced liver fibrosis included age (OR/CI: 1.039/1.016-1.063, P = .001) and platelet count (OR/CI: 0.99/0.986-0.995, P < .001); additionally, IL-28B genetic variants were not associated with liver disease severity.Unfavorable IL-28B genetic variants were associated with advanced liver disease. The genetic effect is limited to patients with HCV-1 infection.

Interleukin 28B rs12979860 genotype and Human Immunodeficiency Virus type 1: Susceptibility, AIDS development and therapeutic outcome

Human Immunodeficiency Virus type 1 (HIV-1) infection and progression varies widely among individuals. Interferon-λ3 exerts anti-HIV function by activating JAK/STAT pathway-mediated innate immunity. Therefore, we aimed to investigate the association between single nucleotide polymorphisms of the interleukin 28B (IL28B) gene, and the risk of acquisition, AIDS development and therapeutic outcome of HIV-1 in a Moroccan population.A total of 266 HIV-1 seropositive and 158 HIV-1 seronegative subjects were enrolled. Genotyping of rs12979860 of the IL28B was performed using a predesigned TaqMan SNP genotyping assay. No significant association was found between IL28B rs12979860 polymorphism and susceptibility to HIV-1 infection and AIDS development (p > .05). However, in HIV-1 treated patients carrying CC genotype had a more pronounced high levels of CD4+ T-cell compared to subjects with TT genotype (p = .0004).Interestingly, regarding HIV-1 viral load no significant differences between IL28B genotypes in treated and untreated patients were observed (p < .05).IL28B rs12979860 polymorphism not influences the susceptibility to HIV-1 and the AIDS development. However, this polymorphism may affect the response to treatment as measured by CD4+ T cell counts.

IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study.

Background and purposeContradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients.MethodsA total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records.Results2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection.ConclusionThis large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3663-6) contains supplementary material, which is available to authorized users.

Association of IL28B rs8099917 genotype and female sex with spontaneous clearance of hepatitis C virus infection: a Japanese cross-sectional study.

Hepatitis C virus (HCV) infection is a serious global health problem. Previous studies have suggested that the interleukin 28B (IL28B) rs8099917 genotype is related to spontaneous clearance of HCV in Caucasian populations. Our objective was to investigate the association of the IL28B rs8099917 genotype with spontaneous clearance of HCV by community-dwelling Japanese. A cross-sectional community-based population study of 993 Japanese residents was conducted. Based on anti-HCV antibody and HCV RNA levels, 50 subjects were assigned to the spontaneous-clearance group, 155 to the chronic-infection group, and 788 to the control group. Logistic regression analysis was done to examine the roles of the IL28B rs8099917 genotype and sex. To analyze the interactions between these factors, an "IL28B rs809991 genotype × sex" interaction term was included in the multivariate analysis. Significantly more subjects in the spontaneous-clearance group than in the chronic-infection group had the favorable IL28B rs8099917 genotype and were female. Multivariate logistic regression analysis extracted the favorable IL28B rs8099917 TT genotype (odds ratio [OR] 9.39; 95% confidence interval [CI], 2.16-40.83, P = 0.003) and female sex (OR, 2.27; 95% CI, 1.16-4.45, P = 0.017) as factors contributing to the spontaneous clearance of HCV. No significant interaction was found between the IL28B rs8099917 genotype and sex (P for interaction = 0.428). Both the favorable IL28B rs8099917 genotype and female sex were associated with the spontaneous clearance of HCV in this Japanese population.

Hepatitis C viremia interferes with serum hepatitis B virus surface antigen and DNA levels in hepatitis B uremics.

Hepatitis B virus (HBV) and HCV might cause reciprocal interference. We aimed to elucidate the influence of HCV and interleukin-28B (IL-28B) genetic variants in the HBV DNA and HBsAg levels in uremic HBV carriers. Assessment of HCV and HBV viral loads, HBsAg levels and IL-28B genotype were performed in 229 HBsAg-positive patients from a cohort of 1,681 uremics. Patients with HCV viremia had significantly lower HBV DNA (2.58±0.80 vs. 3.16±1.48 log IU/mL, p=0.005) and HBsAg levels (1.33±1.35 vs. 2.23±1.31 log IU/mL, p=0.002) compared with those without. IL-28B rs8099917 genotype had no impact on HBsAg and HBV DNA levels. In multivariate regression analysis, HCV RNA levels had a more significant negative correlation with HBsAg levels [β -0.905; 95% confidence interval (CI) -1.477, -0.334; p=0.002] than with HBV DNA levels (β -0.586; 95% CI -1.206, 0.034; p=0.06). The serum HBV DNA and HBsAg levels had a positive correlation (r=0.43, p<0.001) among the 215 HBeAg-negative patients. However, the correlation was not observed in patients with HCV viremia (r=0.23, p=0.29). Linear regression analysis revealed that age (β -0.286; 95% CI -0.043, -0.014; p<0.001) and the HBV DNA level (β 0.373; 95% CI 0.239, 0.549; p<0.001) correlated independently with the HBsAg level among HBeAg-negative patients without HCV viremia, but not among those with concomitant HCV viremia. HCV viremia suppressed both HBsAg and HBV DNA levels. The HBsAg levels correlated with the HBV DNA levels only in patients without concomitant HCV viremia.

IL-28B Polymorphisms Correlated with Treatment Response in HCV-4 Mono-Infected Patients: A Meta-Analysis

BackgroundThe role of interleukin 28B (IL-28B) polymorphisms played in hepatitis C virus (HCV) infection has been gradually explicit, especially in HCV genotype 1, 2 and 3. However, no confirmative conclusion was acquired in genotype 4 HCV patients. Thus we conducted this meta-analysis.MethodsWe searched the commonly used databases both in English and Chinese. Meta-analysis was performed in fixed/random effects models using STATA 12.0 or R software. Publication bias was examined through Egger's test and Begg's funnel plot.ResultsIn total, 11 studies were included in this meta-analysis, encompassing 1284 patients who were mono-infected with HCV-4 and received Peg-interferon (Peg-IFN) plus Ribavirin (Rbv). Around 53.0% patients would achieve sustained virologic response (SVR), 36.6% achieve rapid virologic response (RVR) and 62.4% achieve end of treatment response (ETR). Egyptian patients had a higher rate achieving SVR than non-Egyptian patients (56.3% vs. 47.8%). IL-28B rs12979860 CC genotype not only favored SVR (OR = 3.95, 95%CI = 3.03–5.16), regardless of citizenship, but also favored RVR (OR = 3.82, 95%CI = 2.46–5.95) and ETR (OR = 4.22, 95%CI = 2.81–6.34). IL-28B rs8099917 genotype TT also correlated with SVR (OR = 3.41, 95%CI = 1.92–6.07), but might not with RVR. IL-28B rs12980275 might still correlate with SVR, but warrant more studies to validate.ConclusionsThe favorable IL-28B rs12979860 genotype is a statistically significant predictor of SVR, RVR and ETR in HCV-4 monoinfected patients treated with Peg-IFN plus Rbv. Rs8099917 might predict SVR but not RVR. Egyptian HCV-4 patients would achieve better outcomes than non-Egyptian patients when treated with standard care.

Value of interleukin‐28B genetic polymorphism on retreatment outcomes of chronic hepatitis C genotype 1 relapsers by peginterferon alfa plus ribavirin

Chronic hepatitis C (CHC) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy remains the standard of care for CHC genotype 1 in many Asian countries, and single nucleotide polymorphism or genotype of the interleukin-28B (IL28B) gene is associated with the development of sustained virologic response (SVR). The predictive value of IL28B genotype for retreatment outcomes of patients with CHC was only partly clarified and deserves further investigation. A total of 75 CHC genotype 1 Taiwanese patients who relapsed after 24-week PEG-IFN/RBV combination therapy and received retreatment with a 48-week PEG-IFN/RBV therapy were consecutively enrolled since November 2009. The associations among IL28B rs8099917 genotype, virologic kinetics, and treatment outcomes were evaluated. Rapid virologic response (RVR) at week 4, end-of-treatment virologic response (EOT-VR) and SVR was 37%, 73%, and 52%, respectively. Relapse rate was 29%. None of patients had rs8099917 GG genotype. Patients with TT genotype (n = 54, 72%) had higher rates of RVR (50% vs 5%, P = 0.0002), end-of-treatment virologic response (85% vs 43%, P = 0.0001), and SVR (67% vs 14%, P = 0.0001) than those with GT genotype (n = 21, 28%). Combination of IL28B TT genotype and achieving RVR had 85% positive and 90% negative predictive values of SVR. About half of the Taiwanese CHC relapsers to a previous 24-week combination therapy achieve SVR after retreatment for 48 weeks. IL28B genotype influences on-treatment viral kinetics and SVR rate in these retreated patients. Baseline IL28B genotype and RVR can serve as early predictors for treatment success.

Clinical utility of host genetic IL‐28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin

Host interleukin-28B (IL-28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated. IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin. The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P < 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014). Host IL-28B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype.

Virological Predictors of Response to Retreatment in Hepatitis C Genotype 2 Infected Patients

Background/AimsThe impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown.MethodsOn-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin.ResultsForty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%).ConclusionsPeginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR.

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

To examine the association between the interleukin 28B (IL-28B) genotype and treatment response in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT). We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT. Between February 2010 and April 2013, 278 patients infected with HCV were enrolled in this study. All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin. In addition, 180 μg of peginterferon alpha-2a or 1.5 μg/kg peginterferon alpha-2b per week plus weight-based ribavirin (600-1000 mg/d) were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients. In all of the patients, the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay. HCV RNA was measured using the COBAS TaqMan HCV test. Female patients were dominant in the PNALT group (P < 0.0001). Among 72 HCV genotype 1-infected patients with PNALT, the early virologic response (EVR) rates (P < 0.01) and the sustained virologic response (SVR) rates (P < 0.01) were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype. In HCV genotype 1-infected patients with PNALT, multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type (P < 0.05) and having an EVR (P < 0.01). The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT. The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

Effects of IL28B rs12979860 CC Genotype on Metabolic Profile and Sustained Virologic Response in Patients With Genotype 1 Chronic Hepatitis C

Patients with genotype 1 chronic hepatitis C (G1 CHC) frequently develop steatosis and insulin resistance (IR), caused by metabolic and viral factors. These accelerate the progression of liver disease and reduce the response to therapy. A sustained virologic response (SVR) to therapy in patients with G1 CHC is associated strongly with polymorphisms near the interleukin-28B (IL28B) gene, but the interaction between IL28B genotype and IR, and their combined effects on SVR, have not been defined. We tested the association between the IL28B rs12979860 single-nucleotide polymorphism and metabolic features, including IR, and evaluated their effects on SVR. We performed genotype analysis of IL28B rs12979860 for 434 white G1 CHC patients who underwent consecutive biopsy analysis at 3 tertiary centers. Metabolic profile analyses included assessments of lipid levels and IR by the homeostasis model assessment. Patients with the CC polymorphism in IL28B had higher levels of total and low-density lipoprotein cholesterol, lower levels of triglycerides, and a lower prevalence of IR and moderate-severe steatosis (P < .05) than patients without this genotype. By multiple logistic regression analysis, body mass index (odds ratio [OR], 1.223; P < .001), level of triglycerides (OR, 1.007; P = .006), the CC polymorphism in IL28B (OR, 0.378; P = .001), and levels of HCV RNA greater than 850,000 IU/mL (OR, 1.803; P = .01) were associated with IR. The CC polymorphism in IL28B (OR, 8.350; P < .001) and IR (OR, 0.432; P = .005), but not steatosis (OR, 0.582; P = 0.25), was associated with an SVR. In white patients with G1 CHC, the IL28B rs12979860 CC genotype is associated with reduced IR. IL28B rs12979860 genotype and IR by the homeostasis model assessment strongly affect the outcome of antiviral therapy.

Interleukin 28B rs12979860 (CT/TT) Genotype Is Associated with Milder Hepatic Damage in the Natural Evolution of HCV/HIV Coinfection

Hepatitis C virus (HCV)/human immunodefficiency virus (HIV) coinfection is a major health problem, affecting mostly to individuals with exposure to blood products, as hemophiliacs or intravenous drug users, or those exposed to high-risk sexual practices. Genotyping of interleukin 28B (IL-28B) rs12979860 polymorphism is a useful tool for guiding therapeutic decisions in this disease. On the contrary, there is not enough information on the pathogenic role of this polymorphism in the natural history of the disease. The objective of this study is to describe the relationships between the CT/TT genotype of this polymorphism with viral loads and also with a number of biomarkers of liver function in coinfected patients naïve for treatment for HCV. Seventy-five HCV/HIV coinfected patients were retrospectively recruited in our Hospital from 2010 to 2011. Logistic regression analysis adjusting by [Age], [Sex], [HCV viral genotype], [HCV viral load], [HIV viral load], and [CD4 T cells levels] revealed the IL-28B rs12979860 (CT/TT) genotype as a protective factor against alanine aminotransferase (ALT) levels (>100 IU/L), aspartate aminotransferase (AST) levels (>75 IU/L), and AST-to-platelet ratio index (APRI) score for liver fibrosis (>1.5) [OR, (95% CI), p]: ALT [0.026 (0.001-0.576) 0.021]; AST [0.001 (0.000-0.297) 0.019]; APRI [0.031 (0.002-0.41) 0.008]. Stepwise regression analysis considering the same adjusting variables showed the same results. In consequence, the IL-28B rs12979860 (CT/TT) genotype, which is a marker of poor response to HCV treatment, could be mediating on the contrary a certain protective effect against the hepatic damage caused by this virus in patients coinfected by HIV.

Influence of the Combination of Low-Density Lipoprotein Receptor and Interleukin 28B Genotypes on Lipid Plasma Levels in HIV/Hepatitis C-Coinfected Patients

Influence of the Combination of Low-Density Lipoprotein Receptor and Interleukin 28B Genotypes on Lipid Plasma Levels in HIV/Hepatitis C-Coinfected Patients

IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: Role in the course of chronic viral hepatitis and the development of HCC

A single nucleotide polymorphism (rs12979860 C/T) 3kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory. A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n=199), hepatitis B (n=75), alcohol (n=110), and other causes (n=28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis respectively. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls. A significant difference (p=0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C=99, C/T=137, T/T=38) and those with non-viral cirrhosis (C/C=72, C/T=58, T/T=8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C=23, C/T=50, T/T=12 among OLT patients with cirrhosis complicated by HCC, and C/C=79, C/T=78, T/T=14 among patients with cirrhosis not complicated by HCC (p<0.005). IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC.