Interleukin 28B Single Nucleotide Polymorphisms 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.

Kyushu and Okinawa Population Study (KOPS): a large prospective cohort study in Japan

PurposeThe Kyushu and Okinawa Population Study (KOPS) was established to investigate gene–environmental interactions in non-communicable diseases in Japan. Besides collecting blood samples and anthropometric measurements, we also obtained medical histories,...

Interleukin 28b Single Nucleotide Polymorphism (rs8099917) as a Predictive Factor of Response to Pegylated-IFN/Ribavirintherapy in Chronic HCV Patients

Abstract Background: For Interleukin 28b Single nucleotide poly-morphism (SNP) rs8099917, the favourable T allele is asso-ciated with a higher SVR after PEG-IFN alpha/RBV therapy while the G allele is a risk factor for non-response. Aim of Study: To assess the value of Interleukin 28b (SNP) rs8099917 as a predictor of SVR. Patients and Methods: This study is a retrospective con-trolled study and was performed on a total number of 240 patients who were treated by PEG-IFN alpha/RBV for 48 weeks and (SNP) rs8099917 was done for the all patients. Results: TT genotype was more prevalent in SVR group than TG and GG genotypes. Conclusion: IL-28b single nucleotide polymorphism (SNP) rs8099917 is a strong pretreatment predictor of response to pegylated interferon and ribavirin therapy in egyptian patients chronically infected with HCV genotype 4.

IL-28B variant as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy.

Single-nucleotide polymorphisms (SNPs) of the interleukin-28B (IL-28B) gene are associated with the effectiveness of interferon therapy for chronic hepatitis C infection. Whether the IL-28B genotype affects the course of treatment and the outcomes of patients with advanced hepatocellular carcinoma (HCC) is unknown. We detected the IL-28B SNP (rs8099917) using TaqMan PreDesigned SNP Genotyping Assays to assess the effects of the IL-28B genotype on treatment efficacy and prognosis of patients with advanced HCC treated with hepatic arterial infusion chemotherapy (HAIC) between September 2003 and January 2015. The study included 154 patients who received HAIC to treat advanced HCC, among which 27 (17.5%) had the minor genotype, IL-28B rs8099917 TG or GG, and the others had the major genotype, IL-28B rs8099917 TT. The objective response rates of patients with the minor or major genotype were 51.9% and 29.1% (P=0.022), respectively. Multivariate analysis revealed that the minor genotype remained associated with the response to HAIC (odds ratio, 2.620; P=0.026). The median overall survival of patients with major or minor genotypes was 14.1 and 16.9months, respectively, and the overall survival of patients with the major genotype was significantly shorter than that of patients with the minor genotype (P=0.027). Multivariate analysis revealed that the major genotype was an independent, unfavorable prognostic factor (hazard ratio, 1.720; P=0.024). Consistent results were obtained in selected populations after propensity score matching analysis. The IL-28B SNP (rs8099917) will serve as a useful predictor of the outcomes of patients with advanced HCC treated with HAIC.

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients.

BackgroundSingle-nucleotide polymorphisms (SNPs) that impact on the differential expression of interleukin 28B (IL28B) are implicated in the progression of viral-induced diseases. In this prospective longitudinal cohort study, we evaluated the association between IL28B SNPs rs12979860 and rs8099917 and the clinical outcome of bronchiolitis in pediatric patients.MethodsA total of 682 infants suffering from bronchiolitis, categorized based on the final clinical outcome as mild or severe, were genotyped for IL28B SNPs rs12979860 and rs8099917.ResultsWhen infants were categorized exclusively based on the final clinical outcome, no association was established between IL28B SNPs and the severity of bronchiolitis. However, when stratified by sex, the homozygotes for the minor alleles of rs12979860 (T) and rs8099917 (G) were associated with a mild disease in girls but not in boys.ConclusionSNPs rs12979860 and rs8099917 correlate with the severity of bronchiolitis and display a sex bias, where GG rs8099917 and TT rs12979860 genotypes are associated with a mild disease in girls but not in boys. These findings suggest that innate immunity and female sex links with the outcome of the diseases induced by respiratory viruses, such as RSV.

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection: An updated meta-analysis.

Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection.PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms “interleukin 28B”, “IFN-lambda-3”, “IFNL3”, “single nucleotide polymorphisms”, “SNPs”, “hepatocellular carcinoma”, “HCC”, “liver cancer”.A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57–0.88; OR = 0.82, 95% CI = 0.72–0.94, respectively). Egger test and Begg test revealed no‘ publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis.Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.

IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

Spontaneous viral clearance observed in some patients is one of the variants of the hepatitis C virus (HCV) infection natural history. We aimed to look at the complexity of factors affecting the spontaneous clearance of HCV (SC HCV). A total of 357 anti-HCV positive patients (309 with chronic hepatitis C and 48 patients with SC HCV) were included into the study. We studied the effects of the interleukin-28B (IL-28B) gene polymorphism, gender, age, the routes of virus transmission, past hepatitis C with jaundice, HCV genotype, and hepatitis B virus (HBV) and HIV co-infection on the outcome of HCV infection. Based on the study results, the SC HCV was found in 48 individuals (13.4%). The most significant positive factors affecting the SC HCV included IL-28B single nucleotide polymorphism (SNP) rs12979860 (CC) and SNP rs8099917 (TT) (OR 4.03, p<0.001) and (OR 3.14, p<0.002), female gender (OR 2.72, p<0.001), young age (OR 2.30, p<0.008), and past history of jaundice (OR 5.12, p<0.001). The markers of a past HBV infection were found significantly more often in SC. Positive predictors of the SC HCV include favorable IL-28B genotype, female gender, young age, a history of jaundice, markers of a past HBV infection, the absence of HIV infection, but not the viral genotype.

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients

BackgroundHost single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection.MethodsDNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR.ResultsThe distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant.ConclusionPatients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of “good” response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.

Identification of IL-28B Genotype Modification in Hepatocytes after Living Donor Liver Transplantation by Laser Capture Microdissection and Pyrosequencing Analysis.

The aim of this study is to elucidate the biogenetic modification of donor and recipient interleukin-28B (IL-28B) genotypes in liver graft biopsies after living donor liver transplantation (LDLT) for chronic hepatitis C virus- (HCV-) related, end-stage liver disease. Fifty liver graft biopsies were collected from recipients during LDLT treatment for HCV-related, end-stage liver disease. DNA was extracted from all 50 liver tissues, and the IL-28B single-nucleotide polymorphisms (SNPs) rs8099917 and rs12979860 were studied for allelic discrimination by real-time PCR analysis. Blood samples were obtained from donors and recipients on postoperative day 0 (POD0), POD7, and POD30. We randomly selected five liver biopsies and isolated the hepatocytes by laser capture microdissection (LCM) to evaluate genotype modifications resulting from LDLT. After LDLT, the IL-28B SNP rs8099917 was identified not only in the liver graft biopsies and donors' sera (TT = 41 : 43; GT = 9 : 5; GG = 0 : 2), but also in liver graft biopsies and recipients' sera on POD0 (TT = 41 : 44; GT = 9 : 4; GG = 0 : 2), POD7 (TT = 41 : 30; GT = 9 : 18; GG = 0 : 2), and POD30 (TT = 41 : 29; GT = 9 : 19; GG = 0 : 2). A significant difference was observed between the rs8099917 allele frequencies of liver graft biopsies and recipients' sera on POD30 (p = 0.039). In addition, a significant difference was also noted between the rs12979860 allele frequencies of liver graft biopsies and donors' sera (CT = 49 : 39; TT = 1 : 10) (p = 0.012) and of liver graft biopsies and recipients' sera on POD0 (CT = 49 : 39; TT = 1 : 11) (p = 0.002), POD7 (CT = 49 : 42; TT = 1 : 8) (p = 0.016), and POD30 (CT = 49 : 41; TT = 1 : 9) (p = 0.008). This phenomenon was confirmed by pyrosequencing of hepatocytes isolated by LCM. Following LDLT, the TT-to-GT IL-28B genotype modification predominated in rs8099917, and the CC-to-CT modification predominated in rs12979860. In conclusion, these modified phenomena suggested that the selected donor with a predictable and favourable IL-28B genotype will not confer a benefit on the recipient in the living donor liver transplantation setting.

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil.

HIV and viral hepatitis infections are major causes of chronic disease worldwide and have some similarities with regard to routes of transmission, epidemiology, front barriers faced during access of treatment, and strategies for a global public health response. The objective was to describe the HIV-1 subtypes, viral tropism and single-nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) from a case series of HIV/viral hepatitis coinfected patients from southern Brazil. Clinical and epidemiological data were evaluated by a review of medical records. Periodic blood draws were taken to determine the viral and host characteristics. This study included 38 patients with HIV/HBV or HIV/HCV coinfection; the median age was 49 years. Thirty-seven (97.4%) were on antiretroviral therapy, 32 (84.2%) had an undetectable viral load, a median CD4+ T-cell count of 452 cells/mm3. HIV-1 subtyping showed 47.4 and 31.6% of patients with subtypes C and B, respectively. Analysis of viral co-receptor usage showed a predominance of the R5 variant (64.7%), with no significant difference between the subtypes. Twenty patients with HIV/HCV coinfection were eligible to receive HCV therapy with pegylated-interferon-alpha plus ribavirin, and 10/20 (50%) of them achieved sustained virological response. SNPs of IL28B were evaluated in 93.3% of patients with HIV/HCV coinfection, and 17 (60.7%) presented the CC genotype. In the present case series, a higher frequency of HIV subtype C was found in coinfected patients. However such findings need to be prospectively evaluated with the inclusion of data from regional multicenter analyses.

The impact of genetic variation in IL28B, IFNL4 and HLA genes on treatment responses against chronic hepatitis C virus infection

Single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B), interferon lambda 4 (IFNL4) and the human leukocyte antigen (HLA) gene are associated with treatment responses in patients with chronic hepatitis C (CHC) virus infection treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). We compared the role of IL28B SNPs (rs12979860, rs12980275, and rs8099917), IFNL4 ss469415590 and HLA rs4273729 with treatment outcomes in patients with CHC virus. A total of 520 Iranian patients with CHC infection were enrolled. SNPs in IL28B, IFNL4 ss469415590 and HLA rs4273729 were genotyped by PCR-restriction fragment length polymorphism, TaqMan® Real-Time PCR and direct sequence. Out of 520 CHC treatment-naive patients, 42.9% were infected with HCV-1a, 15.4% with HCV-1b, 9.8% with HCV-2, and 31.9% with HCV-3a. Rapid virologic response (RVR), complete early virologic response (cEVR), and sustained virologic response (SVR) were 53.3%, 73.8%, and 66.7%, respectively. Multivariate logistic regression analysis showed that IL28B rs12980275 and IFNL4 ss469415590 in all HCV genotypes were associated with RVR. In addition, IL28B rs12979860 and RVR in all HCV genotypes and IL28B rs12980275, IFNL4 ss469415590, and HLA rs4273729 in HCV subtypes 1a, 1b, and 3a correlated with cEVR. In patient's achieving-SVR, IL28B rs12980275, and RVR in all HCV genotypes and IL28B rs12979860, IFNL4 ss469415590, and HLA rs4273729 in HCV subtypes 1a, 1b, and 3a were the powerful predictor factors. As the first report of its kind published in Iran, we indicated that beside IL28B SNPs and HLA rs4273729, IFNL4 ss469415590 was a powerful predictor factor for RVR, cEVR and SVR. Genotyping these SNPs may be a helpful priority in the treatment of patients with HCV infection, especially in countries where access to triple or double therapy with a viral protease inhibitor is limited.

IL28B rs12980275 and HLA rs4273729 genotypes as a powerful predictor factor for rapid, early, and sustained virologic response in patients with chronic hepatitis C.

Single-nucleotide polymorphisms (SNPs) in the Interleukin-28B (IL28B) gene and rs4273729 in the human leukocyte antigen (HLA) gene in chronic hepatitis C (CHC) virus infection are important for predicting treatment outcome. In this study, the distribution of IL28B SNPs (rs12979860 and rs12980275) and HLA rs4273729 in rapid virologic response (RVR), complete early virologic response (cEVR) and sustained virologic response (SVR) in HCV Iranian patients with CHC virus infection was assessed. IL28B genotyping and rs4273729 were performed using the amplification refractory mutation system (ARMS)-PCR and direct sequencing in 190 CHC virus infections, respectively. RVR, cEVR, and SVR were 53.2%, 78.9%, and 65.8%, respectively. Multivariate regression analysis demonstrated that the responses significantly predicted SVR in patients with age<40years (p=0.008), HCV genotypes (p=0.032), IL28B rs12979860 CC genotype (p<0.001), rs12980275 AA genotype (p<0.001), rs4273729 GG genotype (p<0.001), RVR (p<0.001) and cEVR (p=0.024). Three critical predictor factors based on RVR response were rs12979860 CC genotype (p=0.033), rs12980275 AA genotype (p<0.001) and rs4273729 GG genotype (p<0.001), while rs12980275 AA (p=0.003) and rs4273729 GG genotypes (p<0.001) predicted cEVR. For the first time in Iran, these results revealed that the rs12980275 and HLA rs4273729 are important for the treatment of CHC infection. These findings may help predict responses to CHC infection treatment and reduce the cost and side effects of therapy.

Prevalence of interleukin-28B single nucleotide polymorphism genotypes in patients with hepatitis C infection in Isfahan, Iran.

Background:Hepatitis C infection is one of the most common causes of liver-related morbidity and mortality. Due to limited efficacy and side-effects of treatment, identification of the determinants of response to treatment is an important issue. Nowadays, genotyping of interleukin (IL)-28B is one of the strongest tests used for prediction of sustained virological response. The prevalence of IL28B genotypes varies across different ethnicities. This study presents data on IL28B single nucleotide polymorphism (SNP) (rs12979860) in a group of Iranian hepatitis C virus (HCV)-infected patients in Isfahan.Materials and Methods:One hundred patients already diagnosed for hepatitis C enrolled the study. Genomic DNA was extracted from whole blood samples. Specific primers were used to amplify IL28B gene (rs12979860). The rs129679860 SNP was genotyped by real-time polymerase chain reaction using TaqMan® probes.Results:The mean age of patients was 33.16 years (25–42 years). Ninety-nine subjects were male and 1 was female. The frequency of HCV genotypes was as follows: Genotype 3a: 53%, genotype 1a: 42%, genotype 1b: 2%, mixed genotype (1a + 3a): 1% and 2%: Nontypable.IL28B rs12979860 genotypes were TT in 17 patients (17%), CT in 41 patients (41%), and CC in the remaining 42 patients (42%).Conclusion:The prevalence of C allele is much higher in our population study than in African American HCV patients (62.5% and 40% respectively), which can explain better response to treatment in our patients.

Combined Effects of 2 Interleukin 28B Polymorphisms on the Therapeutic Outcome of Hepatitis C Patients With Circulating Cryoglobulins.

Chronic hepatitis C is commonly associated with extrahepatic manifestations. Cryoglobulins are observed in 40% to 60% of such patients and their presence seems to modify response to therapy. The new antivirals are greatly improving the sustained virological response (SVR); however, their high cost limits the use, leaving pegylated interferon plus ribavirin (PR) still the standard-of-care therapy worldwide. Since PR therapy is burdened with several side effects, pretreatment predictions of patients who are unlikely to respond to this regimen may avoid ineffective treatment. Variants of the interleukin-28B (IL28B) gene correlate with an SVR to PR, and combined IL28B polymorphisms may improve the prediction of treatment outcome.The potential role of both rs8099917 and rs12979860 IL28B single nucleotide polymorphisms (SNPs) combined with presence of cryoglobulins in predicting SVR to PR in hepatitis C virus (HCV)-chronically infected patients was analyzed in the present study.Single and combined IL28B SNPs (rs12979860 and rs8099917) were analyzed in 64 chronic HCV patients treated with PR showing circulating cryoglobulins and compared to 108 noncryoglobulinemic subjects to verify the predictive value on the SVR.The association of rs12979860CC or rs8099917TT with SVR was confirmed in the noncryoglobulinemic group but not in cryoglobulinemic patients. Moreover, the combined determination of both SNPs improved the prediction of SVR in noncryoglobulinemic patients but not in the cryoglobulinemic subgroup.We report that both single and combined determination of IL28B rs12979860 and rs8099917 SNPs in chronic HCV patients with circulating cryoglobulins treated with PR may have a reduced predictive value of SVR.

The genotype CC of IL-28B SNP rs12979860 is significantly associated with a sustained virological response in chronic HCV-infected Pakistani patients.

To evaluate the association of genetic variation in interleukin 28B (IL-28B) gene and viral factors with treatment outcome in chronic hepatitis C virus (HCV)-infected patients in Pakistan. Patients with chronic HCV infection who received interferon plus ribavirin combination therapy were enrolled in the study. The viral loads were checked at the third and sixth month of treatment and 6 months after the completion of the treatment. Genotyping of single-nucleotide polymorphism (SNP) rs12979860 of IL-28B gene was performed by the restriction fragment length polymorphism method and direct sequence analysis. A total of 111 patients successfully completed antiviral therapy and the follow-up period. Early virological response (EVR) and a sustained virological response (SVR) were achieved in 92 and 91 patients, respectively. Patients infected with HCV genotype 3a had a higher SVR rate compared with other HCV genotypes. A higher C allele frequency (81.9%) was observed in patients with SVR than those with non-SVR (P = 0.00001). The odds ratio of achieving SVR was more than 10-fold greater for the CC genotype than the CT/TT genotypes of SNP rs12979860 (OR 10.351, 95% CI 1.925-55.653, P = 0.006). Other positive predictors observed for SVR were female gender and EVR. The CC genotype of IL-28B SNP rs12979860 is an independent predictive factor for SVR in chronic HCV-infected patients in Pakistan.

Associations between responses to interferon therapy and genetic variation in interleukin-28B and the core region of hepatitis C virus genotype 3a.

The single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) and mutations in the core region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. However, whether this IL-28B SNP affects responses to INF therapy for HCV genotype 3a is not known. The aim of this study is to investigate whether this IL-28B SNP (rs8099917) and specific missense mutations in the HCV core region affect the response to IFN therapy for HCV genotype 3a. Patients (n = 19; median age 44.5) infected with HCV genotype 3a who received IFN therapy were studied. Of the 19 patients, 12 (63.1%) achieved sustained virological response. Of those 12 patients, 11 had the TT genotype (11/16; 68.7%), and one had the TG genotype (1/3; 33.3%). The difference in the sustained virological response rate between IL-28B genotype groups was not significant (P = 0.5232). HCV core region was well conserved; however, polymorphisms at position 72 were identified. Of the 19 HCV samples; 15 carried a glutamic acid at position 72, and these were defined as E type; the others (4/19) were defined as non-E type. Notably, there was a significant difference in the sustained virological response rate between E type and non-E-type; 12 of the 15 patients with E-type achieved sustained virological response, but none of the four patients with non-E-type achieved sustained virological response (P = 0.009). A glutamic acid at position 72 in the core region of HCV genotype 3a was associated with a good response to IFN therapy. J. Med. Virol. 87:1361-1367, 2015. © 2015 Wiley Periodicals, Inc.

Gene polymorphisms of interleukin 28B and the risk to chronic hepatitis B virus infection in Thai

In this study, we aimed to evaluate the effect of two single nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) (rs12979860C/T and rs8099917G/T) on chronic hepatitis B virus (CHB) infection in Thai population. We studied 375 subjects: 83 CHB with hepatocellular carcinoma (HCC) patients, 128 CHB without HCC and 164 individuals with self-limited HBV infection, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan allelic discrimination assay. Results revealed significant risk of IL28B rs8099917T allele associated with CHB without HCC compared with self-limited HBV [odds ratio (OR) (95% confidence interval (CI)) = 2.56 (1.08-6.28), P = 0.019]. The effect of this T allele was similar to that of an autosomal recessive gene in the presence of TT genotype compared with GG and GT genotype [OR (95% CI) = 2.70 (1.11-6.77), P = 0.016, P (logistic regression) = 0.048]. The two locus haplotype analysis of the two IL28B SNP loci did not show any association with CHB (P > 0.05). In conclusion, these results suggested a IL28B rs8099917T allele predispose for susceptibility to chronic HBV infection but not leading to HCC in Thai population.

IL28B genetic variations are associated with treatment response of patients with chronic hepatitis C in a Chinese Han population.

This study aimed to investigate the association between interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) and sustained virological response (SVR) in Chinese Han patients with chronic hepatitis C (CHC) and to analyze the correlations between IL28B SNPs and their personal, virological and clinical characteristics. Altogether 631 Chinese Han individuals, including 297 CHC patients treated with pegylated interferon α plus ribavirin, 14 spontaneous responders to hepatitis C virus (HCV) and 320 healthy controls were enrolled in the study. Two main SNPs of IL28B, rs12979860 and rs8099917, were genotyped using an SNaPshot Multiplex Assay. Associations between IL28B, treatment outcomes and the patients' characteristics were assessed by multivariate logistic regression. The proportion of individuals with the rs12979860 CC or rs8099917 TT genotype was similar in the healthy controls and the CHC patients, although all spontaneous responders presented with both genotypes. Patients with IL28B genotypes had a significantly high rate of rapid virological response (RVR) and SVR. Multivariate analysis revealed that the IL28B SNP rs12979860 CC genotype, being aged <40 years and having a non-genotype 1 (G1) were independent predictors for SVR. The rs12979860 CC genotype and rs8099917 TT genotypes were predictors for RVR. The rs12979860 CC and rs8099917 TT genotypes were more prevalent in patients with a non-G1 genotype than those with G1 genotype. IL28B rs12979860 CC genotype is a significant predictor for SVR and RVR in Chinese Han patients with CHC. Non-G1 HCV genotype is associated with favourable IL28B genotypes.

Importance of virological response in the early stage of telaprevir-based triple therapy for hepatitis C.

To investigate the efficacy of virological response (VR) to telaprevir (TVR)-based triple therapy in predicting treatment outcome of hepatitis C. This prospective, multicenter study consisted of 253 Japanese patients infected with hepatitis C virus (HCV) genotype 1b. All received 12 wk of TVR in combination with 24 wk of pegylated-interferon-α (IFN-α) and ribavirin. Serum HCV RNA was tested at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. VR was defined as undetectable serum HCV RNA. Sustained virological response (SVR) was VR at 24 wk after the end of treatment and was regarded as a successful outcome. Of 253 patients, 207 (81.8%) achieved SVR. The positive predictive value of VR for SVR was 100% at week 2, after which it gradually decreased, and was over 85% to week 12. The negative predictive value (NPV) gradually increased, reaching 100% at week 12. The upslope of the NPV showed a large increase from week 4 (40.6%) to week 6 (82.4%). There was a moderate concordance between the SVR and VR at week 6 (kappa coefficient = 0.44), although other VRs had poor concordance to SVR. Multiple logistic regression analysis extracted VR at week 6 (P < 0.0001, OR = 63.8) as an independent factor contributing to SVR. In addition, the interleukin-28B single nucleotide polymorphism and response to previous pegylated-IFN-α and ribavirin therapy were identified as independent factors for SVR. VR at week 6, but not at week 4, is an efficient predictor of both SVR and non-SVR to TVR-based triple therapy.

Impact of interleukin-28B polymorphism on HCV-1 infected patients treated with response-guided therapy

Summary Background Single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were associated with sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) infected patients treated with a standard 48-week regimen of peginterferon and ribavirin combination. Whether IL28B SNP genotype would be the influential prognosticator for patients treated with response-guided therapy (RGT) is still not well understood. Aims To investigate the impact of IL28B rs809917 genotype on HCV-1 infected patients treated with RGT. Methods A total of 128 consecutive treatment-naive HCV-1 infected patients between July 2006 and July 2011 were analyzed. For rapid virological response (RVR) patients, we allowed an abbreviated 24-week regimen regardless of baseline viral loads; otherwise, a 48-week regimen was implemented (for patients with early virological response). The IL28B rs8099917 SNP genotypes were determined accordingly. Results A total of 117 patients (91.4%) were of rs8099917 TT genotype and 11 (8.6%) were of GT/GG genotype. Eighty-two of the 128 (64.1%) patients achieved SVR, occurring in 54 of 67 RVR patients (80.6%) and 28 of 61 non-RVR patients (45.9%, p p = 0.008) and low relapse rates (28.2% vs. 70.0%; p = 0.006). The multivariate analysis showed that RVR (odds ratio, 4.51; 95% confidence interval, 1.87–10.90; p = 0.001) and rs8099917 TT genotype (odds ratio, 6.91; 95% confidence interval, 1.53–31.17; p = 0.012) were independent factors associated with SVR. Conclusion For HCV-1 infected patients who were treated with RGT, the IL28B unfavorable genotype predicted a higher relapse rate; RVR and IL28B favorable genotype were independent factors associated with SVR in patients treated with RGT.