Outcome Of HCV Infection Research Articles

Maternal hepatitis C virus infection and three adverse maternal outcomes in the United States.

Hepatitis Virus C (HCV) infection rates have trended upwards among pregnant people in the USA since 2009. Existing evidence about HCV infections and maternal outcomes is limited; therefore, we used birth certificate data to investigate the association between HCV infection and maternal health outcomes. We used the 2017 US birth certificate dataset (a cross-section of 1.4 million birth records) to assess the association between prevalent HCV infection and gestational diabetes, gestational hypertension, and eclampsia. Potential confounding variables included prenatal care, age, education, smoking, presence of sexually transmitted infections (STIs), body mass index (BMI), and weight gain during pregnancy. We restricted our analysis to only women with a first singleton pregnancy. Odds ratios were estimated by logistic regression models and separate models were tested for white and Black women. Only 0.31% of the women in our sample were infected with HCV (n = 4412). In an unadjusted model, we observed a modest significant protective association between HCV infection and gestational diabetes (Odds ratio [OR]: 0.83; 95% CI: 0.76-0.96); but this was attenuated with adjustment for confounding variables (Adjusted odds ratio [AOR]: 0.88; 95% CI: 0.76, 1.02). There was no association between HCV and gestational hypertension (AOR: 1.03; 95% CI: 0.91, 1.16) or eclampsia (AOR: 1.15; 95% CI: 0.69, 1.93). Results from the race stratified models were similar to the non-stratified summary models. We observed no statistically significant associations between maternal HCV infection with maternal health outcomes. Although, our analysis did indicate that HCV may lower the risk of gestational diabetes, this may be attributable to confounding. Studies utilizing more accurately measured HCV infection including those collecting type and timing of testing, and timing of infection are warranted to ensure HCV does not adversely impact maternal and/or fetal health. Particularly in the absence of recommended therapy for HCV during pregnancy.

Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets.

The major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the "window-period" of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating with the different outcomes of virus infections was explored in this study. HCV chimera containing the entire HCV core and envelope proteins (CE1E2p7) and GBV-B RNA were intrahepatically injected into four marmosets in each group, respectively. Blood samples were taken from individual animals in an interval of 2 weeks. Viral load and specific T cell responses were detected in two groups of HCV chimera- and GBV-B-infected marmosets. HCV chimera-infected marmosets appeared to have a virally persistent infection over 6 months post inoculation of the virus. Of these, the specific IFN-γ-secretion T cell response slowly developed over 13 to 19 weeks and was maintained at a relatively low level with 40-70 SFC/106 PBMCs, while the specific Treg cell response was rapidly activated over 3 weeks and was maintained at a high level around 5% among lymphocytes. In contrast, GBV-B-infected marmosets presented spontaneous viral clearance within 6 months; the specific IFN-γ-secretion T cell response was quickly established over 5 to 7 weeks and was maintained at a high level with 50-130 SFC/106 PBMCs, while the specific Treg cell response was inactivated and maintained at a baseline below 3% among lymphocytes. In conclusion, the HCV structural proteins inducing immune suppression in the early phase of HCV infection contributed to the viral persistence, of which the activation of Treg cells might play an important role in the inhibition of an effective T cell antiviral response.

The world prevalence, associated risk factors and mortality of hepatitis C virus infection in hemodialysis patients: a meta-analysis.

The worldwide burden of HCV infection among hemodialysis patients has not been systematically examined. A systematic literature search was conducted in MEDLINE and Scopus to determine the worldwide prevalence of HCV infection, risk factors, and clinical outcomes among hemodialysis patients. Random-effect models and meta-regressions were used to generate pooled estimates and assess heterogeneity. Four hundred and seven studies with 1,302,167 participants were analyzed. The pooled prevalence of HCV infection was 21%. The highest prevalence was observed in Africa (28%) and low-income countries (48.5%). A significant prevalence decline was observed following the publication year and was also inversely related to GDP and total population of each country. Factors associated with HCV positivity included younger age, longer dialysis duration, more blood transfusions, and dialyzer reuse. The pooled unadjusted hazard ratio for all-cause mortality was 1.12 (95% CI 1.03-1.22), and the adjusted hazard ratio was 1.21 (95% CI 1.12-1.30) in HCV-infected compared to non-HCV infected patients. HCV infection among hemodialysis patients is a worldwideshared burden and is associated with a higher risk of death. Avoiding unnecessary blood transfusion and dialyzer reuse should be encouraged to prevent HCV transmission in hemodialysis units.

HCV infection characteristics, treatment uptake and outcomes in patient with diabetes mellitus

BackgroundThe interplay between HCV, DM, and DAA therapy is poorly understood. We compared HCV infection characteristics, treatment uptake, and treatment outcomes in patients with and without DM. MethodsA retrospective cohort study was conducted using data from The Ottawa Hospital Viral Hepatitis Program. Statistical comparisons between diabetes and non-diabetes were made using χ2 and t-tests. Logistic regression analyses were performed to assess predictors of DM and SVR.ResultsOne thousand five hundred eighty-eight HCV patients were included in this analysis; 9.6% had DM. Patients with DM were older and more likely to have cirrhosis. HCC and chronic renal disease were more prevalent in the DM group. Treatment uptake and SVR were comparable between groups. Regression analysis revealed that age and employment were associated with achieving SVR. Post-SVR HCC was higher in DM group.ConclusionThe high prevalence of DM in our HCV cohort supports screening. Further assessment is required to determine if targeted, early DAA treatment reduces DM onset, progression to cirrhosis and HCC risk. Further studies are needed to determine if optimization of glycemic control in this population can lead to improved liver outcomes.

Implementation of Microelimination Strategy in Eradication of Chronic Hepatitis C Infection in Patients with Hemophilia in the Northern region of Serbia: Is Eradication Possible?

BackgroundTreating HCV in people with hemophilia prevents the development of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) and greatly increases the quality of life for people living with hemophilia. There are many obstacles in reaching the WHO goal of globally eradicating HCV by 2030, mainly its scale, complexity, and implementation. That is why many countries have implemented a micro-elimination strategy: a pragmatic elimination approach in populations with the most efficacy. The aim of this publication is to present the morbidity and mortality rates, the clinical course and treatment outcomes of chronic HCV infection in people with hemophilia (PwH), as well as to show an example of a successfully conducted HCV micro-elimination strategy among people with hemophilia in the Province of Vojvodina.MethodsA retrospective, single-center study, performed using medical documentation of all registered PwH in the Clinical Center of Vojvodina from 1994. until 2020. It included 74 hemophilia patients, out of which 32 were patients with hemophilia and chronic HCV infection.ResultsThe mean age of HCV-positive positive people with hemophilia (PwH) was 42.3 years, with the duration of infection of 30–35 years. Co-infection with HIV was observed in 6.25% of cases. Furthermore, 18.75% of patients had spontaneous HCV elimination, and 75% were treated with antiviral protocols. Cirrhosis developed in 21.87% with an incidence rate of 0.6 per 100 patient-years. After treatment with Pegylated IFN and ribavirin (RBV), 58.3% achieved SVR. Side effects of IFN-based therapy regimens were recorded in 20.8% of treated (PwH). In 37.5% PWH, DAA protocols were administered, and these patients achieved SVR. HCV- PwH have a statistically higher mortality rate than non-infected people with hemophilia. Among the HCV-positive PwH, hemophilia-related deaths were 6.25%, and HCV-related deaths were 9.37%. Currently, in the Registry of PwH in Vojvodina, there are no patients with active HCV infection.ConclusionThe micro-elimination strategy in the subpopulation of PwH was successfully implemented in Vojvodina by hematologists and infectious diseases specialists in close collaboration.

Predictive Value of RNA Protein Kinase and Interferon-γ for HCV Clearance in Patients with Hepatitis C

Objective — To analyze and study the predict value of serum levels of RNA-dependent protein kinase (PKR), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and interferon gamma (INF-γ) for HCV clearance in patients with HCV infection. Methods — A total of 92 patients with chronic HCV infection (case group), 33 patients with HCV spontaneous resolvers (SR group) and 100 healthy persons (control group) during the same period from January 2018 to October 2019 in our hospital's infection department were collected as the study Object. The basic data and routine biochemical indicators of the three groups of subjects were detected and compared, and the levels of serum PKR, TNF-α, INF-γ and IL-10 were detected by enzyme-linked immunosorbent assay. The ROC work curve analysis was used to evaluate the predictive value of the above immune indicators for HCV clearance in patients with hepatitis C. Results — Compared with the control group and the case group, the serum PKR, TNF-α and IFN-γ levels in the SR group increased, while the IL-10 levels decreased, the difference was statistically significant. Predictive analysis of HCV clearance in chronic hepatitis C patients found that the area under the ROC curve of PKR and IFN-γ were 0.784 (95% CI: 0.704-0.864, P <0.001) and 0.645 (95% CI: 0.538-0.751, P = 0.014), and the optimal cut-off points are 7.00 ng / mL and 101.00 pg / mL, respectively. Conclusion — Both PKR and IFN-γ have a certain predictive value for the clearance of HCV in patients with chronic hepatitis C, which can be used as a potential biomarker for predicting the outcome of HCV infection.

CD8+ T Cell Responses during HCV Infection and HCC.

Chronic hepatitis C virus (cHCV) infection is a major global health burden and the leading cause of hepatocellular carcinoma (HCC) in the Western world. The course and outcome of HCV infection is centrally influenced by CD8+ T cell responses. Indeed, strong virus-specific CD8+ T cell responses are associated with spontaneous viral clearance while failure of these responses, e.g., caused by viral escape and T cell exhaustion, is associated with the development of chronic infection. Recently, heterogeneity within the exhausted HCV-specific CD8+ T cells has been observed with implications for immunotherapeutic approaches also for other diseases. In HCC, the presence of tumor-infiltrating and peripheral CD8+ T cell responses correlates with a favorable prognosis. Thus, tumor-associated and tumor-specific CD8+ T cells are considered suitable targets for immunotherapeutic strategies. Here, we review the current knowledge of CD8+ T cell responses in chronic HCV infection and HCC and their respective failure with the potential consequences for T cell-associated immunotherapeutic approaches.

The relation between interleukin 28B gene polymorphisms (rs8099917 and rs12980275) and the response of treatment of Hepatitis C Virus genotype 4 patients to Sofosbuvir and Daclatasvir therapy

Background: The main line of treatment of hepatitis C in Egypt is direct acting antiviral drugs (DAAs) Objectives: the current study aimed to explore the effect of IL28B genetic polymorphism on HCV infection progression and response to the new treatment in difficulty to treat individuals with HCV genotype 4. Methods: we collected blood samples from 50 healthy individuals as a control and 150 HCV- patients receiving SOF/DCV with ribavirin combination. IL28B (rs8099917, rs12980275) genotyping was implemented using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method to detect its impact on HCV disease outcome. Results: Out of patients, 141(94%) were responders to treatment and 9 (6%) were non- responders. A total of 112 (74.7%) of patients belonged to mild to moderate stages of liver fibrosis and 38(25.3%) had moderate to severe stages. There was a significant increase in severity of fibrosis among non-responders (p value .0.05). significant differences between the different genotypes of IL28B rs12980275 are not detected among the study population. Conclusion: TT genotype of IL28B (rs8099917) may be a protective factor against infection and associated with probability of achieving SVR to combined SOF and DCV therapy in genotype 4 HCV patients. However, GG genotype is negatively associated with HCV infection outcome. IL28B rs12980275 variants had no association with HCV infection.

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

The Pathogen Recognition Receptors (PRRs) is an active protein in the immune system. The PRRs that secreted in the liver and we addressed were L-ficolin, MBL and H-ficolin. Previous studies revealed that both MBL and L-ficolin were hampered the HCV entry and infectivity. However, H-ficolin impact still needs to be addressed more so as determining their role during HCV infection. For these purposes, we aimed to determine the effect of different level in the serum of these proteins on the HCV infection and treatment outcome. Initially, we selected (25) HCV positive patients and (25) HCV negative control patients from the Trent Cohort and Regional Haemophiliac Study and to present the differences in serum concentrations of MBL, H- and L-ficolin. The level of these proteins was measured by ELISA method and compared with each other based on the detected SNPs by PCR and sequencing methods in the responsible genes. Our results showed that the polymorphism at position -221 in the MBL2 promoter significantly reduce the level of MBL protein more than the SNP at position -551. Interestingly, a new deletion of six nucleotides [AGGAAG] detected in the promoter at position -319 to -324 that succeeded by four other mutations at position -328, -336, -349 and -427 in most of the analyzed sequences. The 6bp deletion was statistically decreasing the concentration of MBL below 1µg.mL-1, precisely among non-responder patients. In conclusion, the existence of the new deletion in the promoter region of MBL2 gene and the additional newly detected polymorphisms, reduce the level of MBL protein and as a result impacts on the response to treatment among HCV-infected patients.

Peculiarities of the Expression of Immunohistochemical Marker HCV nS3 in the Autopsy Brain of the Patients Died in the Outcome of Chronic Infection, Caused by Hepatitis C Virus

Background . Brain lesion is one of the most common extrahepatic manifestations of chronic HCV infection. To date, its main clinical and neurometabolic features have been established. However, the morphological picture of HCV-associated cerebral changes and peculiarities of viral molecular markers expression in brain matter remain poorly understood. This significantly limits the possibilities of pathological diagnosis of this disease. Aims . To study the morphological picture of brain lesion during chronic HCV infection and to determine the peculiarities of immunohistochemical (IHC) expression of the HCV NS3 antigen in brain matter. Materials and methods . The study was performed on autopsy brain of 40 patients who died in the outcome of HCV infection and 15 patients died without signs of mental pathology. Complex of pathomorphological and ICH methods was used. Results . It was demonstrated that morphological picture of brain lesion in chronic HCV infection is represented by nonspecific dystrophic, inflammatory and proliferative changes, the severity of which varies significantly depending on the brain departments (p < 0.001). Expression of the NS3 marker is found in all studied brain regions and shows the highest intensity in white matter of cerebral hemispheres and in brain stem (p < 0.05). The ICH reaction of NS3 is manifested in microglia cells, vascular endothelium, inflammatory infiltrate cells and in periventricular ependyma cells. Using correlation analysis method it was found that NS3 expression formed the strongest correlations with such categories as CD68 expression, microgliosis, and axonal degeneration. This allows considering they are the main factors by which HCV realizes its deleterious effect on the brain. Conclusion . Characteristic morphological changes of the brain in chronic HCV infection were studied. The features of ICH expression of the NS3 in various parts of the brain are established. The results can be used to improve pathological diagnosis of brain lesion in chronic HCV infection.

Impact of Toll-like Receptors 2(TLR2) and TLR 4 Gene Variations on HCV Susceptibility, Response to Treatment and Development of Hepatocellular Carcinoma in Cirrhotic HCV Patients

ABSTRACTBackground and Aims: Genetic polymorphisms of Toll-like receptors (TLRs) have been proposed to affect susceptibility to HCV infection and progression to end-stage liver disease. This study was conducted to clarify the association of SNPS of TLR2 and TLR4 with clinical outcome of hepatitis C, response to treatment and development of HCC.Methods: The current study examined 3295 individuals from 725 families that were categorized into groups comprising chronic HCV (CH), spontaneous viral clearance (SC) and control subjects. Treated patients were classified into responders (RT) and non-responders (NRT). In addition, patients with liver cirrhotic (LC), and hepatocellular carcinoma (HCC) were also included. All subjects were genotyped for five single nucleotide polymorphisms (SNPs) of TLR2 and four SNPs of TLR4 and their haplotypes using allelic discrimination real-time PCR.Results: Results demonstrated strong association with allele A of rs13105517 of TLR2 and allele C of rs10116253 of TLR4 with CH in comparison to SC group. However, The peak of risk of HCC was observed with allele C of rs3804099 of TLR2 and C allele of rs10116253 TLR4 (p < 0.001).A strong association was found with allele T of rs1816702 of TLR2 and allele A of rs5030728 of TLR4 in non responder group in comparison to responders (p < 0.001). Haplotypes CAGT of TLR4 and ATAC of TLR2 showed significant association with CH and HCC groups in comparison to other groups.Conclusions: This study shows an association of minor alleles of TLR2 and TLR4 with outcome of HCV infection, response to therapy and development of HCC in cirrhotic patients.

CD40 polymorphisms were associated with HCV infection susceptibility among Chinese population

BackgroundCD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population.MethodsThree single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis.ResultsAfter adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR = 1.368, 95%CI = 1.070-1.749, P = 0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR = 1.397, 95%CI = 1.078-1.809, P = 0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR = 1.337, 95%CI = 1.069-1.673, P = 0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR = 1.351, 95%CI = 1.060-1.702, P = 0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P > 0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P<0.001). In haplotype analyses, compared with the CC haplotype, CT, TC and TT was correlated with an increased risk to infect HCV (P = 0.029, P = 0.047 and P<0.001, respectively).ConclusionsIn conclusion, CD40 polymorphisms were significantly associated with the susceptibility to HCV among Chinese populations.

MICROGLIOSISINWHITEMATTER OF THE BRAIN IN CHRONIC HCV-INFECTION: MORPHOLOGICAL STUDY

The course of a chronic HCV infection in 50% of cases is followed by affection of the brain. Its most frequent manifestations are various cognitive and psychogenic and neurological disorders. It is considered they are based on the activation of HCV infected microglial cells and related to this exitotoxic injury of neurons. According to the data of literature similar changes of microglia in white matter play an important role in a pathogenesis of HIV-associated subcortical dementia. Despite active studying the role of microglia in HCV infection, structural changes and tissue reactions of these cells in nervous tissue remain unexplored. In this regard the purpose of this research was comprehensive immunomorphological research of microglia cells in white matter of different departments of brain in HCV infection. Object of a research was autopsy samples of white brain matter from 40 patients died in the outcome of a chronic HCV infection. 20 people deceased without infectious and mental pathology made up the control group. After histological processing by standard methodic microscopic sections of white matter samples were prepared and stained with review and elective stainings. The immunohistochemical research was conducted using antibodies to virus protein NS3 and antibodies to CD68 microglia cells. The evaluation of microglia cells reactive changes in nervous tissue was performed with submitted earlier methodic. Statistical processing of results was carried out by dispersive Kruskal-Wallis analysis using the SSPS application programs. Level of significance p was accepted equal 0,05. It was established that during chronic HCV infection in white matter of the brain occurs productive changes of microglia cells. They are presented with diffuse and focal anizomorphic microgliosis which expressiveness differs depending on departments of the brain develop (p=0,000). The highest rates of a microgliosis are defined in white matter of brain hemispheres and a brainstem (р=0,05). Morphological features of microgliosis during HCV infection include glial knots formation, phagocytic transformation of microglia with prevalence of amoeboid cells, granular globes appearance, rod microglia congestions in a hippocampus and also degenerative changes in perifocal white matter. These changes of a microglia can be considered as a morphological equivalent of infected with HCV microglia cells activation. The revealed changes indicate that the microgliosis is typical morphological feature of brain injury during chronic HCV infection, and it plays an important role in the pathogenesis of the HCV-associated damage of central nervous system.

Association of PD-1 gene with outcome of hepatitis C virus infection.

Primary hepatitis C virus infection might be spontaneously cleared or become chronic. Polymorphisms in immune regulatory genes might influence the outcome. The aim of this study was to determine the frequency of genotypes and alleles of PD-1.3 and PD-1.5 gene loci in HCV infected patients and their association with the disease outcome. In this study 167 patients with chronic hepatic C and 42 individuals whose infection was spontaneously cleared, and a healthy control group comprising of 300 participants were included. The presence of chronic or spontaneously cleared infection amongst the participants was determined in advance by serologic and molecular methods. Genomic DNA was extracted using salting out method. PD-1 gene polymorphisms assay was performed using PCR-RFLP method. The frequency of alleles of PD-1.3 gene locus was significantly higher in the spontaneously cleared HCV infected group (P = 0.03) as well as the healthy control group (P = 0.04) in comparison to the chronic infected participants. In the case of PD-1.5 locus, there was no association between the frequency of inherited genotype or alleles and HCV infection outcome amongst the three groups. Haplotype analysis showed no statistically significant differences in the frequencies of different haplotypes between the three studied groups. Our finding collectively inferred that individuals with A allele at PD-1.3 locus might clear HCV infection more frequently than those with T allele. Instead, polymorphisms at PD-1.5 locus as well as haplotypes emerged from PD-1.3 G/A and PD-1.5 C/T might not be significant in the HCV infection outcome.

Epidemiology, transmission, diagnosis, and outcome of Hepatitis C virus infection.

Hepatitis C infection is one of the main causes of chronic liver disorders worldwide. Nearly three percent (3%) of the world population has an HCV infection. Prevalence of HCV infection was higher in some groups such as injected drug users (IDUs) and HIV positive populations. Acute hepatitis has proven asymptomatic in most cases, and delay of diagnosis might lead to late onset of hepatocellular carcinoma and cirrhosis. Some host characteristics such as age, gender, body mass index, and viral properties are associated with HCV outcome hepatitis. Although disease progression is typically slow, some risk factors such as alcohol abuse and coinfection of patients with HBV and HIV can worsen the disease. On the other hand, viral overload is one of the main causes of prediction of HCV infection outcome. Prevalence of HCV infection will increase if we do not consider means of transmission, virus behaviors, and immunologic responses. Rapid diagnostic tests can help us to create preventive strategies among undeveloped villages and prisoners. Screening and training of the high-risk population such as IV drug users, dialysis patients, and hemophiliacs must be one of main HCV preventive programs. The present review is intended to help health policymakers to design suitable preventive and management programs.

Impact of Apo E gene polymorphism on HCV therapy related outcome in a cohort of HCV Egyptian patients.

The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to HCV combined therapy. Material and methods: The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). Results: Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value < .001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9–12.1, P-value < .001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0–2.0, P-value < .05). Meanwhile the protective E2 allele was absent in all infected participants. Conclusion: This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.

Down regulation of TRIF, TLR3, and MAVS in HCV infected liver correlates with the outcome of infection.

In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-β (TRIF), and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF, and TRAF6 outcome of HCV infection. The 46 chronic hepatitis C (CHC) patients were screened for LFT (Liver function test), HBsAg, Anti HCV, viral load, histology, and expression of TLR3, MAVS, TRIF, and TRAF6 genes. Out of 46 CHC patients, 7 were on therapy. The 12 healthy controls were screened for LFT, HBsAg, Anti HCV and gene expressions. The gene expressions were studied in liver tissue and measured using semi-quantitative analysis of Western blots. It has been observed that the expression of TRAF6 was independent of HCV infection. The expression of TRIF, TLR3, and MAVS were significantly (P < 0.05) down regulated in CHC (N = 46) compared to healthy controls (N = 12), in high viral load (N = 21) compared to low viral load (N = 25), in HAI (Histology activity index) 1-4 (N = 12), 5-8 (N = 16), 9-12 (N = 8), 13-18 (N = 5) compared to HAI 0 (N = 5) cases. The significant reduction in the expression of TRIF, TLR3, and MAVS was observed in non-responder (N = 3) compared to responder (N = 4) after treatment (P < 0.05). The HCV viral load was positively correlated with the disease severity. The down regulation of TRIF, TLR3, and MAVS expressions in CHC correlates with the disease severity and the outcome of HCV infection.

Association of Genotype and Haplotype of IL-28B Gene with Hepatitis C Infection Outcome in Iran: Spontaneous Clearance Versus Chronic Infection

Background: Spontaneous viral clearance occurs in 10% to 40% of individuals after hepatitis C virus infection. Some polymorphisms in IL-28B gene may influence the outcome of HCV infection. The present study aimed at investigating the genotype and allele frequency of IL-28B rs12979860 and rs8099917 SNPs in HCV infected patients in addition to determining their association with disease outcome. Methods: A total of 302 patients with chronic hepatic C infection and 36 individuals whose infection was spontaneously cleared were included in this case-control study. The presences of chronic or spontaneously cleared infection in participants were determined by serologic and molecular methods. Genomic DNA of the participants was extracted using salting out method. IL-28B/IFN-λ3 gene polymorphisms were conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of CC genotype (P = 0.001) and C allele (P = 0.0007) of IL-28B gene at rs12979860 SNP was significantly higher in participants with spontaneously cleared HCV infection compared to that of those who were chronically infected. In the case of rs8099917 SNP of IL-28B, no correlation was found between frequency of genotype (P = 0.17) or allele (P = 0.12) and HCV infection outcome. The results of haplotype analysis showed the association of CT (P = 0.012) and TT (P = 0.013) haplotypes with spontaneous clearance and chronic infection, respectively. Conclusions: The findings implied that individuals with CC or CT genotype at rs12979860 SNP but rs8099917 SNP was not in association with spontaneous clearance of HCV in an Iranian population with HCV infection.

HLA Class II Genotyping in Chronic HCV Patients

Background: Response to therapy for HCV infection varies among individuals. Studies suggest that this variation may be linked to HLA profile. Objectives: We aimed to identifying the HLA class II DR and DQ genotypes in HCV patients with self limiting versus chronic infection undergoing treatment to reveal any association with HLA. Methodology: Three groups of Patients have been enrolled in the study: Group A 30 patients with self-limiting HCV infection. Group B 30 patients with Sustained virological response. Group C 30 chronic HCV patients non responders to therapy. Samples were subjected to HLA genotyping for 19 HLA-DRB (DRB1*01-16, DRB3-5) and 5 HLADQB (DQB1*02-06) alleles by PCR amplification. Results revealed a significantly higher detection of HLA-DRB1*11(60%, p=0*002) in subjects with self limiting infection in comparison to chronic cases, HLA DRB3 (93.3%, p=0.01) and HLA-DQB1*03 (66.7%, p=0*001). While, HLA-DRB4 detection was significantly higher in chronic HCV patients (80%,p=0*0002)and in patients that failed to respond to treatment (86.7%, p=0.008).Findings revealed that HLA-DRB1*11, DRB3 and DQB1*03 had significantly higher association with subjects with self limiting disease and sustained viral response to treatment. While the HLA- DRB4 showed higher association with non responders to therapy. Conclusion our results confirms that HLA class II type might affect outcome of HCV infection and response to treatment.

Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients

BackgroundHepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC), a common primary liver malignancy, and the third leading cause of cancer-related death. The HCC risk increases with the severity of liver inflammation, and the clinical course of HCV infection depends on a balance between pro- and anti-inflammatory cytokines. The former includes interleukin (IL)-6, while the latter includes IL-10. However, the exact pathogenic mechanisms underlying IL-6 and IL-10 effects remain unclear. MethodsThe present study evaluated 174 chronic HCV Tunisian patients. Polymorphisms of IL-6 (rs1880242, rs1474847, rs2069840, rs1800797, rs1800796, rs2069845, rs2069827, rs1474348, rs1800795), and IL-10 (rs1800896, rs1800871, rs1800872, rs1554286, rs1878672, rs1518111) were determined by real-time PCR. ResultsNotable differences between chronic HCV-infected patients and HCC patients were observed for the three IL-10 SNPs; rs1800871 (−819T/C), rs1800872 (−592A/C), and rs1878672. Carriage of IL-6 rs1800796 G/G genotype, IL-6 rs1474358 C-allele, and IL-6 rs1800797 A-allele was more frequent in chronic HCV-infected patients than in HCC patients. On the other hand, IL-6 rs1474358 GG genotype had a favourable factor for HCC establishment. ConclusionIL-10 and IL-6 SNPs markedly influence the clinical outcomes of HCV infection. These SNPs could be used as biomarkers for early detection and molecular therapy for preventing HCC, and prognostic factors for predicting the clinical outcomes of HCC.