Performance of the tetra-primer PCR technique compared to PCR-RFLP in the search for rs12979860 (C/T) and rs8099917 (T/G) single nucleotide polymorphisms (SNPs) in the IFNL4 gene / Desempenho da técnica tetra-primer PCR em relação a PCR-RFLP na pesquisa de polimorfismos de nucleotídeos únicos (SNPs) rs12979860 (C/T) e rs8099917 (T/G) no gene IFNL4

Single nucleotide polymorphisms (SNPs, rs12979860 e rs8099917) in the Interferon Lambda 4 gene (IFNL4, formerly IFNL3and/or IL28B) has been associated with failure in the innate immune response, sustained virological response in hepatitis C, and HTLV-1-associated myelopathy (HAM) development. To search for these polymorphisms several methodologies can be employed, such as sequencing, real-time or quantitative polymerase chain reaction (qPCR), restriction fragment length polymorphism analysis in PCR products (PCR-RFLP), and tetra-primer PCR. The present study compared the performance of the tetra-primer PCR in relation to the PCR-RFLP, both optimized in the Research HTLV Laboratory of the Center of Immunology of Instituto Adolfo Lutz in São Paulo. One hundred DNA samples obtained from patients of STD/Aids Reference Centre in São Paulo, previously analyzed for IL28B SNPs by PCR-RFLP were selected for analysis, after confirming that they represent all IL28B SNPs patterns described in the literature. The results obtained showed concordance between the PCR-RFLP and the tetra-primer PCR SNPs results, and because of the low cost, easy to perform, and minor employment of biological specimen and reagents, the tetra-primer PCR is of choice to be used in routine. (AU)

Polimorfismos de nucleotídeos únicos (single nucleotide polymorphisms, SNPs rs12979860 e rs8099917) no gene que codifica o Interferon Lambda 4 (IFNL4, antigamente IFNL3 e/ou IL28B) têm sido associados às falhas na resposta imune inata e resposta virológica sustentada na hepatite C, e a mielopatia associada ao HTLV-1 (HTLV-1-associated myelopathy, HAM). A pesquisa destes polimorfismos pode empregar diversas metodologias: sequenciamento, reação em cadeia da polimerase em tempo real ou quantitativa (quantitative polymerase chain reaction, qPCR), análise de fragmentos de restrição enzimática em produtos de PCR (restriction fragment length polymorphism in PCR products, PCR-RFLP) e a tetra-primer PCR. Este estudo comparou o desempenho da tetra-primer PCR em relação a PCR-RFLP, ambas otimizadas no Laboratório de Pesquisa em HTLV do Centro de Imunologia do Instituto Adolfo Lutz de São Paulo. Foram selecionadas 100 amostras de DNA obtidas de pacientes do Centro de Referência e Treinamento em DST/Aids de São Paulo cujos SNPs na IL28B foram anteriormente determinados por PCR-RFLP e representaram todos os perfis descritos em literatura. Os resultados obtidos mostraram concordância entre elas, e pelo fato da tetra-primer PCR ter menor custo, ser de fácil execução, empregar menos tempo, insumos e material biológico, é a técnica de escolha para uso em rotina. (AU)

Respiratory syncytial virus: host genetic susceptibility and factors associated with disease severity in a cohort of pediatric patients.

BACKGROUND: Respiratory syncytial virus (RSV) infections are the leading cause of hospitalization in young children. We assessed the epidemiology, severity, clinical characteristics, molecular profile and genetic factors of RSV infections compared to acute respiratory illness (ARI) caused by other respiratory viruses. METHODS: Prospective cohort study was conducted from 2017 to 2018 with children under 2 years old hospitalized with ARI. Detection of respiratory viruses was carried out using RT-PCR. RSVs were genotyped via nucleotide sequencing, and host interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) were determined using SNP TaqMan® Genotyping Assays. RESULTS: A total of 468 children were included; 288 (61.5%) had an infection by a single virus: 202 (70.1%) cases by RSV followed by rhinovirus 36 (12.5%) and influenza 16 (5.6%). Of the RSV cases, 36% were genotyped with a higher prevalence of RSV B (62.1%). The RSV group presented median age of 2.7 months (1.6-6.8), higher frequency in: intensive care unit admission (p = 0.004), mechanical ventilation use (p = 0.018), wheezing (p < 0.001), antimicrobial use (p < 0.001) and low oxygen saturation (p < 0.001). Prematurity (27.2%) was the most frequent comorbidity. RSV patients without comorbidities demonstrated a higher frequency in the combination of IL28B rs12979860 CT/IL28B rs8099917 TG and IL28B rs12979860 TT/IL28B rs8099917 TT genotypes. Viral coinfection was detected in 27 (5.7%) children, with the most frequent being RSV and rhinovirus (14.2%). CONCLUSIONS: This study highlighted the burden of RSV infection in children under 2 years of age, without comorbidities, with a higher need for pediatric ICU admission. Some IL28B allele combinations had a significant association with RSV frequency of infections.

The effects of IL28B rs12979860 and rs8099917 polymorphism on hepatitis B infection.

OBJECTIVE: The purpose of this study was to evaluate the relationship of IL28B rs12979860 and rs8099917 polymorphisms with the clinical, histological, and virological outcomes of patients with chronic hepatitis B (CHB) also the treatment responses of patients who received Nucleos(t)ide analogs (NAs) therapy. METHODS: This study included 152 CHB patients who were underwent liver parenchymal biopsy. The IL28B rs12979860 and rs8099917 polymorphism were genotyped using the TaqMan assay. RESULTS: The IL28B rs12979860 CC and IL28B rs8099917 TT were identified as the genotypes with the highest frequency in all patients. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency. The frequency of IL28B rs8099917 TG genotype was significantly different between patients with hepatitis B, who has histologically defined liver cirrhosis and no-fibrosis (p=0.02). In addition, a statistically significant correlation was found between the presence of IL28B rs8099917 G allele and virological unresponsiveness to NAs treatments in CHB patients (p=0.028). CONCLUSION: The presence of the IL28B rs8099917 G allele in CHB patients might be associated with the risk of developing cirrhosis and virological unresponsiveness to NAs treatments.

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients.

In various genome-wide correlation studies, interleukin (IL)28B gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of IL28B (rs12979860) in patients with chronic hepatitis C and assess the IL28B polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of IL-28B (rs12979860) was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (p < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore IL-28B (rs12979860) SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.

Association of Interleukin-28B Polymorphisms (rs12979860 C/T, rs12980275 A/G, rs8099917 T/G) and Risk of Hepatocellular Carcinoma in an Iranian Population.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The association of interleukin 28B (IL-28B) polymorphisms and HCC has been investigated in several populations. However, the findings are controversial. This study aimed to address the association between IL-28B polymorphisms (rs 8099917 T/G, rs12979860 C/T, rs12980275 A/G) and the risk of HCC in an Iranian population. METHODS: We have evaluated the association between IL-28B polymorphisms (rs 8099917 T/G, rs12979860 C/T, rs12980275 A/G) and HCC in 180 Iranian individuals (60 patients with HCC and 120 healthy matched controls) using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Single nucleotide polymorphism (SNP) association analysis and also haplotypes were estimated using the SNPstats online software. RESULTS: There was no significant association between these three polymorphisms of IL-28B and HCC (P>0.05). Moreover, haplotype analysis showed no significant association between the haplotypes and HCC. CONCLUSION: There was no association between IL-28B polymorphisms and HCC in an Iranian population.

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

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

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

BACKGROUND: Autoimmune 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. AIM: Our aim was to investigate for the first time the incidence and clinical significance of PD1.3 and IL28B rs12979860 in AIH. METHODS: Two 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. RESULTS: The 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. CONCLUSIONS: The 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.

IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy.

BACKGROUND: Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. RESULTS: Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. CONCLUSION: Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients.

WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan-genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first-in-class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV-4. METHODS: Samples were collected at week zero. One hundred and thirty-one patients who reached the end of treatment (at week 12) were divided into three groups, according to their interleukin 28B genotype: Group A included 31 patients (CC genotype), group B included 79 patients (CT genotype) and group C had 21 patients (TT genotype). All patients received treatment for 3 months in the form of sofosbuvir plus daclatasvir with ribavirin (in case of cirrhotic patients) or without ribavirin (in case of non-cirrhotic patients). RESULTS AND DISCUSSION: Sustained virological response rate was significantly higher in patients with IL28B (CC genotype) vs. (non-CC genotype) (100 vs.88%) (p < 0.0001).These patients also showed lower rates of post-treatment relapse and non-response, compared with the CT and TT patients (0% vs. (7.59% and 28.5%, respectively) (p < 0.0001). Also, patients with CC genotype showed higher sustained virological response than non-CC genotypes on both cirrhotic (100% vs. 68.75%) and non-cirrhotic patients (100% vs. 91.66%) (p ≤ 0.0001). WHAT IS NEW AND CONCLUSION: Our results suggest that IL28B genotype contributes to the prediction of response to sofosbuvir plus daclatasvir.

Predictive power of Interleukin-28B gene variants for outcome of Hepatitis C Virus genotype 4 in Egyptians: A systematic review and meta-analysis.

BACKGROUND: An advanced liver fibrosis did not abolish an Egyptian ethnicity as a favourable predictor for hepatitis C genotype 4 (HCV-GT4) outcome, that raises genetic issues. PATIENTS AND METHODS: Multiple databases were searched from inception up to 1 April, 2020 for all studies included Egyptians, whose were genotyped for Interleukin-28B (IL-B28) in the setting of HCV. The pooled odds ratios (ORs) were based on a fixed or random effect model as appropriate. RESULTS: In total, 33 studies included 5,538 Egyptians from 9 governorates. Of these, 4088 patients had chronic HCV-GT4, 373 resolvers (spontaneously cleared the virus), and 1077 non-infected subjects. The pooled prevalence of CC and CT/TT rs12979860 genotypes among chronic HCV-GT4 were 32%, and 68%, respectively. The pooled sustained virologic response (SVR) was achieved in 54% of 2,622 patients received Pegylated-interferon and Ribavirin. Compared with chronic HCV-infected patients, the favorable CC genotype was over-represented in the healthy subjects (30% vs. 45%), and HCV resolvers (28% vs. 59%). The CC genotype carriers were two-times more likely to resist HCV infection (vs. CT/TT: OR=1.93, P<0.001), three-times (OR=3.31, P<0.001) to clear the virus spontaneously, and six-times to achieve interferon-induced SVR (ORcorrected=6.03; P<0.001). The rs8099917 TT carriers were associated with a higher rate of SVR (vs. wild GT/GG, 74% vs. 38%), with 3-fold probability achieving SVR (ORcorrected=3.42, P<0.001). CONCLUSIONS: Polymorphisms near the IL-28B gene protect against infection and persistence of HCV, and predict SVR.

IL-27 along with IL-28B ameliorates the pulmonary redox impairment, inflammation and immunosuppression in benzo(a)pyrene induced lung cancer bearing mice.

AIMS: The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8+ T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue. MAIN METHOD: BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysis, cell cytotoxicity assay, real-time PCR assay etc. were performed to evaluate the modulatory role of IL-27 and IL-28B. KEY FINDINGS: We observed that IL-27 and IL-28B were able to suppress the expression of lung cancer-associated NFkB, COX-2, and iNOS. The expression of TNF-α, PCNA and some matrix remodeling enzymes were also modulated upon IL-27 and IL-28B treatment. Although the population of lung residing CD8+ T cells in tumor bearing lung tissue were unresponsive but the activity of systemic CD8+ cells was increased. SIGNIFICANCE: Results hinted that IL-27 along with IL-28B were able to ameliorate various hallmarks ranging from angiogenesis to inflammation associated with the BaP-induced lung carcinogenesis. From this study, we propose that IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer.

Association between IL28B Polymorphisms and Outcomes of Hepatitis B Virus Infection: A meta-analysis.

BACKGROUND: Interleukin (IL) 28B polymorphisms encoding pro-inflammatory and anti-inflammatory cytokines trigger diverse clinical outcome of hepatitis virus infection. However, there is controversy concerning the association of IL28B polymorphisms with the outcome of hepatitis B virus (HBV) infection, with several studies obtaining inconsistent results. We performed a meta-analysis to evaluate the role of 3 single nucleotide polymorphisms (SNPs) rs12979860, rs12980275 and rs8099917 in the progression of HBV infection, overall and by ethnicity. METHODS: Searched PubMed, Embase and Wiley Online Library electronic databases using 'interleukin 28B', 'IL 28B', 'IL 28B polymorphism', 'hepatitis B virus', 'HBV', and performed meta- analysis for rs12979860, rs12980275 and rs8099917 in Asian and Caucasian populations under the dominant recessive and allele model. RESULTS: Eighteen studies were found in total and used for this meta-analysis, including 5587 cases and 4295 controls. The IL28B polymorphism rs12979860 had no association with HBV persistence (CC vs CT + TT: OR = 0.86, 95% CI = 0.76-1.00; TT vs CT + CC: OR = 1.14, 95% CI = 0.76-1.70; T vs C: OR = 1.03, 95% CI = 0.94-1.13). Similarly, neither rs12980275 nor rs8099917 had associations with HBV persistence (rs12980275 in AA vs AG + AA: OR = 1.15, 95% CI = 0.96-1.38; rs8099917 in TT vs GT + GG: OR = 1.15, 95% CI = 0.96-1.39). There was also no significant association of IL28B polymorphisms with persistent HBV infection in Asians or Chinese. There was no evidence of an association of rs12979860 with the HBV-related hepatocellular carcinoma susceptibility (T vs C: OR = 1.53, 95% CI = 0.96-2.43). CONCLUSION: IL28B polymorphisms had no association with the outcome of HBV infection overall, nor in the Asians and the Chinese. These 3 SNPs might not be relevant to the development of HBV infection.

Association between Hepatitis C Virus Viremia and the rs12979860, rs2228145 and rs1800795 SNP (CT/AC/GG) Genotype in Saudi Kidney Transplant Recipients.

BACKGROUND: Hepatitis C virus (HCV) is a major health problem, particularly in high-risk groups such as kidney transplant recipients, where it can adversely affect graft survival and increase the relative risk for mortality. Recently, the role of genetic variation among HCV patients in determining the outcome of infections has been under investigation. OBJECTIVE: To investigate the association of single-nucleotide polymorphisms (SNPs) rs12979860 (located within the interleukin-28B locus), rs2228145 (interleukin-6 receptor) and rs1800795 (interleukin-6 promoter) with HCV viremia in renal transplant patients. MATERIALS AND METHODS: In this analytical cross-sectional study, 149 kidney transplant recipients, 82 males (median age: 41 years) and 67 females (median age: 45 years), were screened for HCV RNA in blood using real-time polymerase chain reaction and genotyped by sequencing (rs12979860) and restriction fragment length polymorphism (rs2228145 and rs1800795). RESULTS: HCV RNA was detected in 17 (11.41%) of the 149 patients. There was no statistically significant association between the studied SNPs and HCV viremia. However, a combination of the CT/AC/GG genotype was significantly associated with HCV viremia (odds ratio: 5.4). The genotype AA of rs2228145 in the IL-6 receptor was associated with viremia levels of >105 copies/ml (odds ratio: 5.96). CONCLUSION: To the best of the authors' knowledge, this is the first study that has shown that the CT/AC/GG genotype has an impact on HCV viremia in kidney transplant patients. Therefore, such SNP genotypes may potentially be used to identify transplant patients at risk of HCV infection.

"Here Today, Gone Tomorrow" or "Here Today, Stay a Long While": The Divergent Paths of Two Host Factors Important in Viral Infections.

Host factors are critically important in governing the susceptibility and severity of most viral infections. The importance of these host factors is governed by the prevalence of the virus and the availability of effective therapeutic and/or preventive measures. This commentary highlights two such host factors that were initially judged to be important but over time have moved in opposite directions: hepatitis C virus and the IL28B locus as well as HIV and the Δ32-CCR5 mutation.

Persistence rate of cervical human papillomavirus infections and abnormal cytology in Rwanda.

OBJECTIVES: In this study, we determined the incidence and persistence of human papillomavirus (HPV) strains and of squamous intraepithelial lesions (SIL) or worse cytology in 237 HIV-positive and HIV-negative Rwandan women and whether the interleukin (IL)-28B single nucleotide polymorphism (SNP) at rs12979860 correlated with susceptibility to and persistence of HPV infection. METHODS: Cervical samples were collected at baseline and after 9, 18 and 24 months for a 40-HPV DNA screening test and a ThinPrep Pap test. Genotyping of the IL-28B SNP rs12979860 was performed using real-time polymerase chain reaction (PCR). RESULTS: Chronic high-risk (HR) HPV infections occurred in 56% of HIV-positive women, while no HIV-negative women developed HPV chronicity. High-grade SIL (HSIL) or cancer was diagnosed in 38% of HIV-positive women with persistent HR-HPV infections. HIV and HR-HPV positivity at baseline were factors associated with an increased risk of HPV persistence. Additionally, HR-HPV positivity at baseline was associated with an increased risk of developing HSIL or worse cytology. The unfavourable T/x genotype at rs12979860 is common among Africans, and women with this genotype were found to be more commonly infected with HPV. CONCLUSIONS: HPV screening in Rwanda may help to identify women at risk of developing cervical cancer and polymorphism in IL-28B may be associated with risk of contracting  HPV infection.

IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment.

BACKGROUND: Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment. METHODS: A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics. RESULTS: A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001). CONCLUSIONS: An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA.

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.

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

INTRODUCTION: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: 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.

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

AIM: 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. BACKGROUND: HCV is considered essentially hepatotropic and is a major health problem around the world. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Relationship between interleukin-28B single nucleotide polymorphism and spontaneous clearance and antiviral efficacy of hepatitis C virus infection in Huzhou area of Zhejiang Province / 中华传染病杂志

Objective To analyze the effect of single nucleotide polymorphism ( SNP) rs8099917 of interleukin-28B ( IL-28B) on spontaneous virus clearance and the efficacy of antiviral therapy in hepatitis C virus (HCV) infected patients in Huzhou area of Zhejiang Province.Methods A total of 268 HCV-infected patients were enrolled.The high sensitive HCV RNA quantification , HCV genotype and the IL-28B rs8099917 SNP were detected at baseline.One hundred and sixty-three patients received pegylated interferon α-2a ( Peg-IFNα-2a) and ribavirin (RBV) combined antiviral therapy (referred as PR treatment) for 48 weeks, who were followed up for 24 weeks.The remaining 44 patients were treated with sofosbuvir and daclatasvir for 12 weeks. The virological response of patients with different IL-28B rs8099917 genotypes was monitored.The count data was compared by χ2 test.Results The distributions of IL-28B rs8099917 SNP were 84.33%for TT genotype and 15.67%for GT genotype, while the GG genotype was not detected.Of the 135 patients with acute HCV infection, 61 cases had spontaneous viral clearance , 74 cases were converted to chronic infection.The spontaneous clearance rates were 47.11% for TT genotype and 28.57% for GT genotype.There was no significant difference of the spontaneous clearance rate between TT and GT genotype (χ2 ＝1.072, P＝0.30). In 163 chronic hepatitis C (CHC) patients with PR treatment, the rate of sustained virological response (SVR) after 24 weeks follow-up was 86.50%(141 cases).SVR rate in patients with TT genotype was significantly higher than those with GT genotype (91.67%vs 47.36%, χ2 ＝28.212, P＜0.05).There was no statistically significant difference of the SVR rates between genotype 1b and 2a (χ2 ＝1.525, P＞0.05).In 44 patients received sofosbuvir and daclatasvir treatment , both SVR rates of TT genotype and GT genotype were 100%. Conclusions In Huzhou area of Zhejiang Province , there is no significant correlation between IL-28B rs8099917 genotype and spontaneous clearance in patients with acute HCV infection , but the genotype of IL-28B rs8099917 is valuable for the prediction of PR treatment efficacy , the SVR rate of the TT genotype is superior to the GT genotype.The SVR rate can reach 100% in patients received combination therapy of sofosbuvir and daclatasvir independent of polymorphism of IL-28B.