Outcome Of Hepatitis C Virus Infection Research Articles

Genetic variants of Nuclear Factor-Kappa B were associated with different outcomes of Hepatitis C virus infection among Egyptian patients.

Hepatitis C virus (HCV) is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC). Nuclear factor kappa B (NF-κB) is a transcription factor that functions in health and disease. Genetic variants of the NF-κB gene can affect its function and are associated with chronic inflammatory changes and malignant transformation. This case-control study is aimed to determine the possible association between NF-κB genetic variants and different outcomes of HCV infection among Egyptian patients. 295 subjects were recruited with allocation of participants in the representative group according to results of serological and molecular tests. Patients in the case group (group A) were further divided into three subgroups; subgroup I, mild chronic HCV, subgroup II, cirrhosis, and subgroup III, HCC subgroups (59 for each subgroup), group B included participants who experienced spontaneous viral clearance (n=59). All were compared to matched healthy control subjects, Group C (n=59). All participants were genotyped for NF-κB polymorphisms, rs11820062 by TaqMan assay and rs28362491 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Risk analysis indicated that subjects carrying the rs11820062 A genotype are more susceptible to HCV infection (OR: 3.1; 95%, CI= 1.4-6.9). Subjects carrying the rs28362491 insertion genotype are at more risk of progression to cirrhosis when compared to healthy-controls and patients with mild chronic HCV (OR:7.7; 95% CI=2.4-24.3 and OR:5.1, 95% CI= 1.7-15.7, respectively) and also are at more risk of developing HCC when compared to healthy controls (OR:2.6; 95% CI= 0.94-7.3). Polymorphisms affecting NF-κB different genes would modulate HCV infection susceptibility and clinical disease progression among Egyptian patients.

Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis

Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2=100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2=79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2=10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. None.

Frequency of the Main Human Leukocyte Antigen A, B, DR, and DQ Loci Known to Be Associated with the Clearance or Persistence of Hepatitis C Virus Infection in a Healthy Population from the Southern Region of Morocco: A Preliminary Study.

Hepatitis C Virus (HCV) infection represents a significant global health challenge, with its natural course largely influenced by the host's immune response. Human Leukocyte Antigen (HLA) molecules, particularly HLA class I and II, play a crucial role in the adaptive immune response against HCV. The polymorphism of HLA molecules contributes to the variability in immune response, affecting the outcomes of HCV infection. This study aims to investigate the frequency of HLA A, B, DR, and DQ alleles known to be associated with HCV clearance or persistence in a healthy Moroccan population. Conducted at the University Hospital Center Mohammed VI, Marrakech, this study spanned from 2015 to 2022 and included 703 healthy Moroccan individuals. HLA class I and II typing was performed using complement-dependent cytotoxicity and polymerase chain reaction-based methodologies. The results revealed the distinct patterns of HLA-A, B, DRB1, and DQB1 alleles in the Moroccan population. Notably, alleles linked to favorable HCV outcomes, such as HLA-DQB1*0301, DQB1*0501, and DRB1*1101, were more prevalent. Conversely, alleles associated with increased HCV susceptibility and persistence, such as HLA-DQB1*02 and DRB1*03, were also prominent. Gender-specific variations in allele frequencies were observed, providing insights into genetic influences on HCV infection outcomes. The findings align with global trends in HLA allele associations with HCV infection outcomes. The study emphasizes the role of host genetics in HCV infection, highlighting the need for further research in the Moroccan community, including HCV-infected individuals. The prevalence of certain HLA alleles, both protective and susceptibility-linked, underscores the potential for a national HLA data bank in Morocco.

Treatment Outcomes of HCV Infection in People Living with HIV: A Case Series from a Single Center in Korea.

Limited information is available on the clinical course and treatment outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in Korea. A retrospective case series was conducted of patients with HIV-HCV coinfection who received interferon (IFN)-based or direct-acting antiviral (DAA) treatment for HCV at a tertiary care hospital between 2000 and 2023. Early virological response (EVR) was defined as a 2-log reduction in HCV RNA levels or undetectable HCV RNA levels at treatment week 12. A sustained virologic response (SVR) was defined as undetectable HCV RNA at 12 weeks after treatment completion. Of the 33 patients with HIV-HCV coinfection, 19 received anti-HCV treatment, of whom 12 received IFN-based treatment and 10 received DAA treatment. The median age at the time of anti-HCV treatment was 49 years (interquartile range, 42-57 years) and 15 patients (79%) were male. Of the 12 patients who received IFN-based anti-HCV treatment, 10 showed EVR and 8 achieved SVR. However, 2 patients who achieved SVR experienced recurrence of HCV infection during follow-up; therefore, the overall success rate of IFN-based treatment was 50% (6/12). All 10 patients (including 3 in whom IFN-based treatment failed) who received DAA treatment (5 with previous anti-HCV treatment and 5 treatment-naïve), achieved SVR and did not experience recurrence of HCV infection during follow-up; therefore, the overall success rate of DAA treatment was 100%. In Korean patients with HIV-HCV coinfection, treatment outcomes were better with DAA treatment than with IFN-based treatment.

KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection

In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in the outcome of individuals with chronic hepatitis C virus (HCV) infection in Egypt. The study was carried out under an IRB-approved protocol. Sequence-Specific-Primer-PCR (SSP-PCR) was used for KIR genotyping of germline DNA extracted from peripheral blood leukocytes or from the non-tumor liver of 83 HCC patients, 100 patients with chronic HCV infection without HCC, and 120 matched healthy controls. Out of the 83 HCC patients, only 7 (8.4%) were treated by interferon and/or interferon Ribavirin combination, while for the remaining patients 50 (60.2%) received no prior HCV therapy and 26 (31.3%) were treated with direct-acting antiviral (DAA). Our results showed that KIR haplotype AA that contains more inhibitory KIR genes and fewer activating genes was observed with a significantly lower frequency in HCC patients (6/83, 7.2%) compared to chronic HCV (27/100, 27.0%) (p = 0.0005, OR = 0.21 [0.08–0.53]) and healthy controls (29/119, 24.4%) (p = 0.001, OR = 0.24 [0.09–0.61]). In addition, the frequency of genotype 6 (G6) which contains all the KIR genes was significantly high in the HCC patients (16/83, 19.3%) compared to chronic HCV (8/100, 8.0%) (p = 0.02, OR = 2.7 [1.11–6.79]) and healthy controls (8/119, 6.7%) (p = 0.006, OR = 3.31 [1.35–8.16]). Activating KIR genes 2DS1 and 3DS1 were significantly higher in HCC patients (48/83, 57.83% and 45/83, 54.22%) compared to the chronic HCV patients (36/100, 36% and 34/100, 34%), p = 0.028, 0.027, respectively. Our results are contrary to a prior work on HCC from patients with HCV who were mostly treated by interferon-based therapies. In conclusion, KIR haplotype AA has an important role in host defense against HCC progression especially in patients treated by DAA, suggesting an important role of the KIR genotype status on the outcome of chronic HCV infection.

Genetic Polymorphism in Toll-Like Receptor 3 and Interferon Regulatory Factor 3 in Hepatitis C Virus-Infected Patients: Correlation with Liver Cirrhosis.

Host genetic factors could play a primary role in determining the risk for cirrhosis development in chronic hepatitis C virus (HCV)-infected patients. We designed this work to study the effect of single-nucleotide polymorphism (SNP) in Toll-like receptor 3 (TLR3) and interferon regulatory factor (IRF) on the risk of HCV-related cirrhosis. This study enrolled 139 Egyptian HCV-infected patients. They were divided into patients with cirrhotic (56) and noncirrhotic (83) liver. Genotyping of rs3775291 F459F (+1234C/T) and rs3775290 L412F (+1377C/T) in TLR3 and IRF3 rs2304204 (-925A/G) was performed by restriction fragment length polymorphism-polymerase chain reaction. Although there is no significant difference in genotype and allele distribution of +1377C/T of TLR3 gene between cirrhotic and noncirrhotic subjects, CC (odds ratio [OR] = 1.572, 95% confidence interval [CI]: 0.781-3.164); TT (OR = 1.463, 95% CI: 0.351-6.104) genotypes might be considered as risk factors for liver cirrhosis. On the contrary, the analysis revealed that only one genotype (CC) and one allele (C) were detected in +1234C/T SNP, with the total disappearance of CT/TT genotypes and T allele in all subjects. On the contrary, lower frequency has been found for the AG genotype of the IRF3 (-925A/G) gene in cirrhotic patients compared with noncirrhotic ones, indicating that AG is a protective genotype (OR = 0.509, 95% CI: 0.256-1.012). Our data stressed the association of AG genotype SNP in IRF3 (-925A/G) in protection against the worth outcome of HCV infection.

Toll-like Receptor Response to Hepatitis C Virus Infection: A Recent Overview.

Hepatitis C virus (HCV) infection remains a major global health burden, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that detect pathogen-associated molecular patterns and activate downstream signaling to induce proinflammatory cytokine and chemokine production. An increasing number of studies have suggested the importance of TLR responses in the outcome of HCV infection. However, the exact role of innate immune responses, including TLR response, in controlling chronic HCV infection remains to be established. A proper understanding of the TLR response in HCV infection is essential for devising new therapeutic approaches against HCV infection. In this review, we discuss the progress made in our understanding of the host innate immune response to HCV infection, with a particular focus on the TLR response. In addition, we discuss the mechanisms adopted by HCV to avoid immune surveillance mediated by TLRs.

Association of Vitamin D Gene Polymorphisms With HCV Infection Outcome.

Background: Vitamin D derivatives and their receptor (VDR) are immune-response modulators in many diseases including malignancies, metabolic conditions, and infections. We hypothesized that one or more variants of VDR single nucleotide polymorphisms (SNPs) are associated with hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. Materials and Methods: A total of 861 subjects were recruited and classified as spontaneous viral clearance (SVC, n = 127), chronic hepatic cirrhosis (CHC, n = 392), and HCC (n = 342). Standard routine laboratory tests were performed and clinical features noted. All individuals were genotyped for seven SNPs spanning the VDR using real-time PCR. Results: Genotype frequencies of SNPs rs7970376, rs11568820, rs4516035, rs2228570 (Fok1), rs1544410 (Bsm-1), and rs731236 (Taq1), but not rs739837, were variously altered in CHC and HCC compared with SVC, and in HCC compared to CHC (all p < 0.001). The most powerful was rs7970376, which brought an OR (95% CI) of 7.14 (4.64–10.98) for HCC compared to SVC (p = 0.001). The carriage of the AGTAC haplotype of five SNPs were linked to CHC compared to SVC at OR 2.88 [95% CI 1.2–6.9] (p = 0.017) and with HCC compared to CHC at OR 1.54 [95% CI = 1.04–2.27 (p = 0.031). Conclusion: SNPs in VDR may have a potential role in the outcomes of patients with HCV infection. VDR SNPs; rs7970376, rs11568820, rs4516035, rs2228570 (Fok1), rs1544410 (Bsm-1), and rs731236 (Taq1) could be used as molecular markers to predict the risk of HCC.

Assessment of Renal Function in Egyptian HCV Patients Treated with Combination Therapy of Sofosbuvir and Daclatasvir

BACKGROUND: According to the most recent Egyptian demographic health census, the estimated Hepatitis C virus (HCV) prevalence in the 15–59 age range was 14.7%. Globally, the incidence of renal impairment in HCV-positive individuals is 40% higher than in HCV-negative patients. HCV-induced renal impairment can range from mild-to-severe, and it frequently complicates the treatment outcome of HCV infection. AIM: This study aimed to explore the changes in renal function in Egyptian HCV patients treated with a combination of Sofosbuvir (SOF) and Daclatasvir (DCV). METHODOLOGY: Six hundred and eleven chronic HCV patients treated with SOF-DCV were enrolled. Patients were classified into three groups according to their baseline renal function: unimpaired group (estimated glomerular filtration rate [eGFR] ≥ 90 ml/min/1.73 m2), mildly impaired group (eGFR of ≥60–89 ml/min/1.73 m2), and moderately impaired group (eGFR of ≥30–59 ml/min/1.73 m2). Every month during treatment and at 24 weeks after treatment (sustained virological response 24), the eGFR level was evaluated. RESULTS: Our findings indicated that the eGFR level was significantly increased (p &lt; 0.001) in all groups during the treatment but subsequent decline (p &lt; 0.001) in all groups was documented after 6 months of treatment. Multivariate analysis identified baseline renal impairment (&lt;90 ml/min/1.73 m2, p &lt; 0.001) and baseline anemia (p &lt; 0.001) as independent risk factors for renal function deterioration at the end of treatment. CONCLUSION: Clinical physicians should closely monitor renal function in patients treated with SOF-DCV. Furthermore, anemia therapy prior to SOF-DCV treatment should be recommended.

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 &lt;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 &lt;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.

Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.

OBJECTIVESInjection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data on this topic are available in Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).METHODSWe used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of a questionnaire survey on lifetime risk factors for HCV infection were analyzed according to a self-reported history of injection drug use (PWID vs. non-PWID group).RESULTSAmong the 2,468 patients, 166 (6.7%) were in the PWID group, which contained younger patients (50.6±8.2 vs. 58.2±13.1 years) and a higher proportion of male (81.9 vs. 48.8%) than the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not significantly differ between the groups.CONCLUSIONSAs of 2019, PWID constituted a minority of HCV-infected people in Korea. The epidemiological characteristics, but not treatment uptake and outcomes, were different between the PWID and non-PWID groups. Therefore, active HCV screening and treatment should be offered to PWID in Korea.

Association of HLA Class II Alleles with Outcome of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis

Context: Hepatitis C Virus (HCV) infection is a major cause of chronic cirrhosis and hepatocellular carcinoma. Approximately 30% of infected persons with HCV spontaneously clear the viral infection; but, some of the remaining patients develop chronic HCV. Studies show that HLA molecules play an important role in the outcome of HCV infection by influencing the efficiency of the antiviral immune response to HCV infection. It is now known that polymorphisms in HLA loci are associated with HCV susceptibility or clearance. The purpose of the present study was to systematically review the studies that reported the association of HLA class II alleles (HLA-DQ and HLA-DR) with the outcome of HCV infection. Evidence Acquisition: Studies were identified by searching electronic databases, including PubMed and Scopus. A total of 12,265 relevant studies were identified by the electronic search, of which a total of 19 eligible papers were identified that were meta-analyzed for the association between HLA class II alleles and the outcome of HCV infection. Results: Subjects carrying HLA-DQB1*0301, HLA-DQB1*0501, HLA-DRB1*1303, HLA-DRB1*1201, HLA-DRB1*0401, HLA-DRB1*0101, and HLA-DRB1*1101 alleles were significantly associated with higher spontaneous clearance of HCV infection. Conclusions: The data from the current study confirm that several polymorphisms in HLA-DQ and HLA-DR loci are correlated with the clearance of HCV infection. Identifying these polymorphisms may contribute to a better understanding of immune mechanisms of HCV clearance or persistence.

Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population.

BackgroundKIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of KIR/HLA-C genes and the outcomes of HCV infection in a high-risk Chinese population.MethodsIn this case-control study, four single nucleotide polymorphisms (SNPs) of KIR/HLA-C genes (KIR2DS4/KIR2DS1/KIR2DL1 rs35440472, HLA-C rs2308557, HLA-C rs1130838, and HLA-C rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs.ResultsAfter logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229–1.987, P < 0.001; OR = 2.134, 95% CI: 1.180–3.858, P = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all P trend < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function.Conclusion KIR2DS4/KIR2DS1/KIR2DL1 rs35440472-A and HLA-C rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.

Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion.

Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.

Genetic variant of RXR involved in the vitamin D metabolic pathway was linked to HCV infection outcomes among a high-risk Chinese population.

Genetic variation of related genes in Vitamin D (VD) metabolic pathway played an important role in antiviral immune response and chronic hepatitis C virus (HCV) infection. Retinoid X receptor (RXR) is one of the key genes in the metabolism pathway of VD. This study aims to investigate the effect of single nucleotide polymorphisms (SNPs) in RXR on the outcomes of HCV infection. Three SNPs (RXRɑ-rs4842194, rs1045570 and RXRβ-rs2076310) were genotyped using Sequenom MassARRAY platform in 515 spontaneous clearance subjects, 830 persistent infection subjects, and 1062 uninfected subjects. Multivariate stepwise regression analyss was used to identify the prediction factors for HCV infection outcomes. The USCS Brower and RNAfold web serves were performed to further explore the potential biological functions of positive SNPs. The results of logistic regression analysis after adjusting for age, gender and types of high-risk population showed that subjects with RXRβ rs2076310-T (recessive model: adjusted OR=1.598, 95%CI=1.126-2.267, P=0.009; additive model: adjusted OR=1.196, 95%CI=1.011-1.416, P=0.037) had a significantly increased possibility of HCV infection chronicity. Rs2076310, age, types of high-risk population and aspartate aminotransferase were independent predictors of chronic HCV infection (P<0.05). And the area under the receiver operating characteristic curve of combined effects of these factors was 0.679. Bioinformatics analysis indicated that rs2076310 could affect the gene expression level by affecting the transcriptional regulatory activity of the corresponding gene region. These findings indicated that genetic variation of RXRβ was associated with the risk of HCV infection chronicity among a high-risk Chinese population.

Low Mannose Binding Lectin, but Not L-Ficolin, Is Associated With Spontaneous Clearance of Hepatitis C Virus After Infection.

Some individuals can spontaneously clear the hepatitis C virus (HCV) after infection, whereas others develop a chronic infection. The exact mechanism of this phenomenon is unknown. We aimed to evaluate the association of plasma levels of MBL, L-ficolin, and cytokines with outcome of HCV infections in two groups of patients who cleared HCV spontaneously (CHS), and who developed chronic HCV infections (CHC). Altogether, 86 patients and 183 healthy controls were included. Of 86 patients, 36 had CHS and 50 had CHC. Concentrations of plasma MBL and L-ficolin were measured in patients and controls. Twenty plasma cytokines and adhesion molecules, including GM-CSF, ICAM-1, IFN-γ, IFN-α, IL-1α, IL-1β, IL-10, IL-12p70, IL-13, IL-17A, IL-4, IL-8, IP-10, MCP-1, IL-6, MIP-1α, MIP-1β, sE-Selectin, sP-Selectin, and TNF-α, were determined in all patients and randomly selected 45 controls. The level of MBL was significantly lower in subjects with CHS than in healthy controls (median: 293.10 vs. 482.64 ng/ml, p = 0.008), whereas the level of MBL was significantly higher in patients with CHC than in controls (median: 681.32 vs. 482.64 ng/ml, p = 0.001). No such differences in plasma L-ficolin were observed. Plasma levels of all cytokines and adhesion molecules, except ICAM-1, were significantly higher in patients than in controls. Moreover, patients with CHC had significantly higher levels of IFN-γ, IFN-α, IL-1α, IL-10, IL-13, IL-4, IL-6, and TNF-α than those with CHS. These findings implicate that lower levels of plasma MBL, together with lower levels of above mentioned cytokines may play a part in virus clearance of HCV infection.

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection

Introduction: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. Methods: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. Results: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. Conclusions: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.

HCV and HEV: two players in an Egyptian village, a study of prevalence, incidence, and co-infection.

The highest recorded hepatitis C virus (HCV) prevalence worldwide is in Egypt. A high prevalence of hepatitis E virus (HEV) in chronic liver disease has been reported. The aim of this study was to study prevalence, incidence, and outcome of HCV infection in an Egyptian Nile Delta village and the relation between HEV infection and HCV-related chronic hepatic affection. This prospective cohort study included 2085 Nagreej village residents. Mass HCV screening was conducted and testing for HEV antibodies among HCV-infected patients performed. The annual incidence of HCV was recorded. Five hundred five (24.22%) of the tested villagers were positive for HCV RNA. Prevalence escalated with age and male sex. The main recorded risk factors were a history of surgery, dental procedures, hospitalization, blood transfusion, and antischistosomal treatment. HEV IgG antibody was positive in 71.4% of individuals with chronic HCV and 96.1% with advanced liver disease (cirrhosis ± hepatocellular carcinoma (HCC)). After 1 year, 29 of the 1390 HCV Ab negative villagers had a positive HCV PCR, placing an annual incidence of new HCV infections at 2.09%. The Egyptian HCV prevalence remains high with infection particularly among the elderly. The annual incidence in a small Nile Delta village is 2.086%. HCV-HEV co-infection may lead to a worse prognosis among Egyptians with chronic liver disease.Electronic supplementary materialThe online version of this article (10.1007/s11356-020-09591-6) contains supplementary material, which is available to authorized users.

Innate Immunity in Hepatitis C Virus Infection.

Activation and viral control of the innate immune response are hallmarks of hepatitis C virus (HCV) infection and are major determinants of spontaneous clearance or progression to chronic infection and liver disease. In this review, we provide a contemporary overview of how HCV is sensed by the host cell to trigger innate immune activation and the mechanisms deployed by the virus to evade this response. Type I and III interferons (IFNs) are crucial mediators of antiviral innate immunity against HCV, and we specifically highlight the importance of IFN-λ host genetics for the outcome of HCV infection. Last, we focus on the proinflammatory responses elicited by HCV infection and describe our current understanding of how interleukin (IL)-1β signaling and cross talk between the IL-1β and IFN signaling pathways lead to sustained inflammation and increased risk of liver pathology.

Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients.

Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma. An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) activity is crucial to prevent NAFLD installation. The present study aims to investigate the associations between two common PPARGC1A polymorphisms (rs8192678 and rs12640088) and the outcomes of HCV infection in a North African context. A series of 592 consecutive Moroccan subjects, including 292 patients with chronic hepatitis C (CHC), 100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay. PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection (adjusted ORs = 0.76 and 0.79 respectively, P > 0.05, for both). Furthermore, multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression (OR = 0.71; 95% CI 0.20-2.49; P = 0.739; OR = 1.28; 95% CI 0.25-6.54; P = 0.512, respectively). We conclude that, in the genetic context of South Mediterranean patients, rs8192678 and rs12640088 polymorphisms of PPARGC1A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV.