Outcome Of HCV Infection Research Articles

Association of Interleukin-27 rs 153109 Single Nucleotide Polymorphism with Spontaneous Resolution of Hepatitis C Virus - Genotype 4a Infection in Egyptian Patients.

HCV is a major global health problem. IL-27 is a member of the IL-6/IL-12 cytokine family with a broad range of anti-inflammatory properties. Recent studies highlighted the effect of a SNP in the IL-27 promoter region on modulating the progression of infectious diseases and individual responses to therapy. The present study investigated the potential role of (-964 A/G) SNP in the promoter region of IL-27p28 gene (alleles rs153109) on the outcome of HCV infection among genotype 4a infected patients. HCV genotyping confirmed that all of the HCV-infected patients had genotype 4a infection. Genomic DNA was extracted from 111 patients with chronic HCV infection, 42 spontaneous resolvers (SR) and 16 healthy controls. IL- 27p28.rs153109 genotyping was assessed using PCR-RFLP then confirmed by DNA sequencing. The frequency of IL-27-p28.rs153109AA, AG, and GG genotypes among chronically infected subjects were 74.8 %, 25.2%, and 0% while among the SR, they were 57.1%, 35.7%, and 7.14%, respectively. Our data show the unique presence of G/G genotype in the SR group (3 patients; 7.14%). Moreover, the "G" allele frequencies among chronic and resolved subjects were 12.6% and 25.0%, respectively (p=0.0136). Importantly, subjects with the GG genotype were more likely to clear their HCV infection than those with the AA genotype (p=0.0118). HCV genotype 4a subjects with the IL-27-p28.rs153109 A/G and G/G genotype were more likely to clear their HCV infection. Therefore, we propose IL- 27p28.rs153109SNPas a genetic biomarker for predicting HCV infection outcome.

HCV infection status and risk factors in remunerated blood donors in Jiangsu province

To investigate the infection status of HCV in remunerated blood donors and risk factors in Jiangsu province. A Cross-sectional study was conducted among people aged >50 years. Questionnaires were used to collect the information about their demographic characteristics and risk behaviors, and venous blood samples were collected from them to detect HCV anti-body, HCV-RNA and other biochemical indicators. EpiData and Stata were used for data entry and statistical analysis. The overall HCV sero-prevalence rates were 22.55% and 61.05% among remunerated blood donors. Data from multiple stepwise regression analysis showed that alanine aminotransferase(ALT)(adjusted OR=1.38, 95%CI: 1.18-1.62)and aspartate aminotransferase(AST)(adjusted OR=1.30, 95%CI: 1.10-1.54)were associated with the outcomes of HCV infection, and fasting plasma glucose(adjusted OR=1.17, 95%CI: 1.01-1.35)were associated with HCV RNA viral loads. The prevalence of HCV infection in remunerated blood donors was high, clinical ALT, AST and fasting plasma glucose levels were associated with the risk for HCV infection and HCV RNA viral load.

Follow-up of patients with chronic hepatitis C and a sustained viral response.

Patients with chronic hepatitis C who achieve a sustained virological response (SVR) after antiviral treatment have improved survival and liver-related morbidity compared to non-SVR patients. However, long-term follow-up studies in SVR patients have shown that the regression of fibrosis varies and the risk of liver-related complications remains, even in the absence of cirrhosis. While patients with cirrhosis are still at risk of hepatocellular carcinoma, comorbidities such as diabetes, obesity or alcohol consumption may play a major role in the outcome of liver disease in SVR patients without cirrhosis. The risk of re-infection is high in patients with a persistent risk of contamination such as IV drug users or men who have sex with men. Thus, in the era of highly efficient DAAs regimens, monitoring after a cure of HCV infection remains a major challenge in SVR patients. This review describes long-term HCV infection and liver-related outcomes in SVR patients, as well as the profile of patients who are still at risk of progression, and monitoring techniques including non-invasive markers for the assessment of fibrosis.

Altered natural killer cells subsets distribution in children with hepatitis C following vertical transmission.

Natural killer (NK) cells number, phenotypes and function have been evaluated in many studies in adults with hepatitis C as compared with healthy controls or dynamically during interferon-based and interferon-free treatments. Overall, in adults with chronic infection number of circulating NK cells has been reported to be lower when compared to spontaneous resolvers and healthy subjects. Different studies yielded inconsistent findings due to patient and virus heterogeneity. To evaluate NK cells in children according to the different outcomes of the infection. In this cross-sectional study, we examined numbers and phenotypes of circulating NK cells from a homogenous cohort of Italian children with vertically acquired hepatitis C. We compared 31 children who developed chronic infection with nine who presented spontaneous clearance and 13 controls. CD56(+) CD3(-) NK cell numbers were consistently lower in the persistently infected group (P = 0.03 and 0.04). This decrease was due to depletions of CD56(dim) NK cells (P = 0.03 chronic infection vs. spontaneous clearance), while CD56(bright) NK cells were expanded (P = 0.03). No significant difference was found in the frequencies of CD56(+) CD16(+) and CD56(dim) CD16(-) cells. Perforin expression was higher in children with chronic infection (P = 0.03 vs. spontaneous clearance). Altered NK cells number and phenotypes could impact the outcome of HCV infection in children following vertical transmission. This study suggests for the first time that NK cells cytolytic function, featured by CD56(dim) cells, contributes to the elimination of HCV in children presenting spontaneous clearance.

HCC Burden in Egypt

Hepatocellular carcinoma (HCC) is the commonest primary cancer of the liver. Geographical distribution of HCC varies throughout the world with an incidence rate ranging from 2.1 in Central America to 35.5 in Eastern Asia. The burden of HCC has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. This may be attributed to high prevalence of HCV in Egypt. Egypt has a high incidence of HCC about 21% in cirrhotic Egyptian patients. HCV and HBV infections, diabetes and smoking are the main determinants of HCC development in Egypt. Occult HBV infection may influence the outcome of HCV infection leading to development of HCC. An active surveillance and secondary prevention programs for patients with chronic hepatitis are the most important steps to reduce the risk of HCC.

P104: Serum biomarker profile can predict the outcome of acute HCV infection

P104: Serum biomarker profile can predict the outcome of acute HCV infection

Modeling the effect of HIV coinfection on clearance and sustained virologic response during treatment for hepatitis C virus

BackgroundHIV/hepatitis C (HCV) coinfection is a major concern in global health today. Each pathogen can exacerbate the effects of the other and affect treatment outcomes. Understanding the within-host dynamics of these coinfecting pathogens is crucial, particularly in light of new, direct-acting antiviral agents (DAAs) for HCV treatment that are becoming available. Methods and findingsIn this study, we construct a within-host mathematical model of HCV/HIV coinfection by adapting a previously published model of HCV monoinfection to include an immune system component in infection clearance. We explore the effect of HIV-coinfection on spontaneous HCV clearance and sustained virologic response (SVR) by building in decreased immune function with increased HIV viral load. Treatment is modeled by modifying HCV burst-size, and we use clinically-relevant parameter estimates.Our model replicates real-world patient outcomes; it outputs infected and uninfected target cell counts, and HCV viral load for varying treatment and coinfection scenarios. Increased HIV viral load and reduced CD4+ count correlate with decreased spontaneous clearance and SVR chances. Treatment efficacy/duration combinations resulting in SVR are calculated for HIV-positive and negative patients, and crucially, we replicate the new findings that highly efficacious DAAs reduce treatment differences between HIV-positive and negative patients. However, we also find that if drug efficacy decays sufficiently over treatment course, SVR differences between HIV-positive and negative patients reappear. ConclusionsOur model shows theoretical evidence of the differing outcomes of HCV infection in cases where the immune system is compromised by HIV. Understanding what controls these outcomes is especially important with the advent of efficacious but often prohibitively expensive DAAs. Using a model to predict patient response can lend insight into optimal treatment design, both in helping to identify patients who might respond well to treatment and in helping to identify treatment pathways and pitfalls.

EFTUD2 Is a Novel Innate Immune Regulator Restricting Hepatitis C Virus Infection through the RIG-I/MDA5 Pathway.

The elongation factor Tu GTP binding domain-containing protein 2 (EFTUD2) was identified as an anti-hepatitis C virus (HCV) host factor in our recent genome-wide small interfering RNA (siRNA) screen. In this study, we sought to further determine EFTUD2's role in HCV infection and investigate the interaction between EFTUD2 and other regulators involved in HCV innate immune (RIG-I, MDA5, TBK1, and IRF3) and JAK-STAT1 pathways. We found that HCV infection decreased the expression of EFTUD2 and the viral RNA sensors RIG-I and MDA5 in HCV-infected Huh7 and Huh7.5.1 cells and in liver tissue from in HCV-infected patients, suggesting that HCV infection downregulated EFTUD2 expression to circumvent the innate immune response. EFTUD2 inhibited HCV infection by inducing expression of the interferon (IFN)-stimulated genes (ISGs) in Huh7 cells. However, its impact on HCV infection was absent in both RIG-I knockdown Huh7 cells and RIG-I-defective Huh7.5.1 cells, indicating that the antiviral effect of EFTUD2 is dependent on RIG-I. Furthermore, EFTUD2 upregulated the expression of the RIG-I-like receptors (RLRs) RIG-I and MDA5 to enhance the innate immune response by gene splicing. Functional experiments revealed that EFTUD2-induced expression of ISGs was mediated through interaction of the EFTUD2 downstream regulators RIG-I, MDA5, TBK1, and IRF3. Interestingly, the EFTUD2-induced antiviral effect was independent of the classical IFN-induced JAK-STAT pathway. Our data demonstrate that EFTUD2 restricts HCV infection mainly through an RIG-I/MDA5-mediated, JAK-STAT-independent pathway, thereby revealing the participation of EFTUD2 as a novel innate immune regulator and suggesting a potentially targetable antiviral pathway. Innate immunity is the first line defense against HCV and determines the outcome of HCV infection. Based on a recent high-throughput whole-genome siRNA library screen revealing a network of host factors mediating antiviral effects against HCV, we identified EFTUD2 as a novel innate immune regulator against HCV in the infectious HCV cell culture model and confirmed that its expression in HCV-infected liver tissue is inversely related to HCV infection. Furthermore, we determined that EFTUD2 exerts its antiviral activity mainly through governing its downstream regulators RIG-I and MDA5 by gene splicing to activate IRF3 and induce classical ISG expression independent of the JAT-STAT signaling pathway. This study broadens our understanding of the HCV innate immune response and provides a possible new antiviral strategy targeting this novel regulator of the innate response.

Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection.

Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).

IFNL4 and IFNL3 associated polymorphisms strongly influence the spontaneous IFN-alpha receptor-1 expression in HCV-infected patients.

Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.

Serum biomarker profile can predict the outcome of acute HCV infection

Introduction: The natural course of acute hepatitis C virus infection is highly diverse varying between spontaneous clearance of the virus to evolution of chronic hepatitis C (HCV) virus infection. The aim of this study was to identify parameters during early time points of infection predicting the natural course of the infection by analysis of serum IP-10 levels and other cytokines and chemokines thus enabling identification of patients not achieving spontaneous viral clearance who might require antiviral treatment. We performed multianalyte profiling of 50 cytokines and chemokines in the serum using the BioPlex method. Serum samples from 26 patients with acute symptomatic HCV infection recruited within the German Hep-Net-acute HCV-III cohort were analyzed together with ten clinical parameters at the time of diagnosis of infection. To identify profiles characterizing spontaneous sustained viral resolvers we performed principal component analysis (PCA) using Qlucore Omics Explorer Software (Qlucore, Lund, Sweden).

IFN-λ: A New Class of Interferon with Distinct Functions-Implications for Hepatitis C Virus Research

Pegylated interferon-α and ribavirin (PEG-IFN/RBV) is widely used to treat chronic hepatitis C virus infection with notorious adverse reactions since the broad expression of IFN-α receptors on all nucleated cells. Accordingly, a Type III IFN with restricted receptors distribution is much safer as an alternative for HCV therapy. In addition, single nucleotide polymorphisms (SNPs) near the human IFN-λ3 gene, IL-28B, correlate strongly with the ability to achieve a sustained virological response (SVR) to therapy with pegylated IFN-α plus ribavirin in patients infected with chronic hepatitis C. Furthermore, we also discuss the most recent findings: IFN-λ4 predicts treatment outcomes of HCV infection. In consideration of the apparent limitations of current HCV therapy, especially high failure rate and universal side effects, prediction of treatment outcomes prior to the initiation of treatment and developing new alternative drugs are two important goals in HCV research.

Role of Interleukin-10, Interleukin-12 in the Response Prediction during Combined PEG Interferon-alpha 2a and Ribavirin Therapy in Patients with Chronic Hepatitis C

Background: Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%-25% in rural communities. Sustained virological response in genotype 4 Egyptian patients treated with PEG-IFN alfa-2a and ribavirin was estimated around 60%. It is of major interest for both patient care and economic approach to predict failure of response. Several factors have been shown to influence response to antiviral treatment. Cytokines play an important role in the pathogenesis, progression and treatment outcome of HCV infection. Aim: The current study was designated to assess serum interleukin-10 and interleukin-12 levels in CHC genotype 4 patients and investigate their benefit as predictors of antiviral response. Methods: This study was conducted on a total number of 70 participants admitted to Hepatology and Gastroenterology Department in NHTMRI (National Hepatology & Tropical Medicine Research Institute). The participants of this study were divided into two groups as following; Group I: 20 healthy subjects (as controls), while the cases in Group II: 50 patients with chronic hepatitis C (CHC) genotype 4. Results: Our results showed that IL-12 and IL-10 levels were higher in patients with HCV infection than in control participants and were significantly higher in the group of the sustained responders, compared with non-responders. Serum IL-10 level showed a sensitivity and specificity of 76.7% and 73.3% respectively while serum IL-12 level showed sensitivity and specificity of 90% and 75% respectively. Conclusion: These results demonstrate the beneficial role ofIL-10, IL-12 in achieving an SVR during IFN-alpha and ribavirin therapy

A New Twist to a Chronic HCV Infection: Occult Hepatitis C.

Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990–2014). Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12–18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

IFNL3 genotype is associated with differential induction of IFNL3 in primary human hepatocytes.

Lambda interferons (IFNLs) have potent antiviral activity against HCV, and polymorphisms within the IFNL gene cluster near the IFNL3 gene strongly predict spontaneous- and treatment-related HCV infection outcomes. The mechanism(s) linking IFNL polymorphisms and HCV control is currently elusive. IFNL induction was studied in primary human hepatocytes (PHH) from 18 human donors, peripheral blood mononuclear cells (PBMCs) from 18 human donors, multiple cell lines and induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-hepatocytes) from 7 human donors. After stimulation with intracellular RNA and infectious HCV, quantitative PCR (qPCR) primers and probes were designed to distinguish and quantify closely related IFNL messenger (m)RNAs from IFNL1, IFNL2 and IFNL3. PHH demonstrated the most potent induction of IFNLs, although had lower pre-stimulation levels compared to PBMCs, monocytes and cell lines. PHH stimulation with cytoplasmic poly I:C induced >1,000-fold expression of IFNL1, IFNL2 and IFNL3. PHH from donors who were homozygous for the favourable IFNL3 allele (IFNL3-CC) had higher IFNL3 induction compared to PHH from IFNL3-TT donors (P=0.03). Baseline IFNL mRNA expression and induction was also tested in iPSC-hepatocytes: iPSC-hepatocytes had significantly higher baseline expression of IFNLs compared to PHH (P<0.0001), and IFNL3 induction was marginally different in iPSC-hepatocytes by IFNL genotype (P=0.07). Hepatocytes express IFNLs when stimulated by a synthetic viral RNA that signals the cell through the cytoplasm. IFNL induction may be greater in persons with the favourable IFNL3 allele. These data provide insight into the strong linkage between IFNL3 genetics and control of HCV infection.

Clinical significance of the CCR5delta32 allele in hepatitis C.

BackgroundThe CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection.Methods CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance.ResultsCarriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35–0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99–1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4).ConclusionsThe CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

Study of toll-like receptor 7 expression and interferon α in Egyptian patients with chronic hepatitis C Infection and Hepatocellular Carcinoma

BackgroundHepatitis C virus is considered to be one of the most important devastating causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. Toll-like receptor 7 (TLR7) is a pathogen-recognition receptor that is expressed on innate immune cells. It recognizes viral RNA which induces its activation with a subsequent increase in IFN-α transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence. The aim of the workWas to investigate the expression of TLR7 in peripheral blood of patients with chronic HCV infections and patients with HCC, comparing it with normal individuals, and correlating it with both serum levels of IFN-α and viral load. ResultsThe results of this study showed a significant decrease in TLR7 expression in patients with chronic HCV and no detection at all in patients with HCC, in addition a significant negative correlation was observed between levels of TLR7expression and interferon α when compared to viral load. ConclusionDown regulation of TLR7 expression in HCV and HCC patients may contribute to the decrease of IFN-α and increase in viral load. These results raise the possibility that by targeting TLR7 with high affinity pharmacological stimulants may be able to control HCV infection by induction of IFN-α and direct activation of antiviral mechanisms in hepatocytes. Additionally, they provide insight about the potential use of TLR7 as a new set of molecular markers for prognosis and outcomes of chronic HCV infection and HCC.

Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females

Toll-like receptors 7 (TLR7) play a crucial role in provoking an immune response in HCV infection. We aimed to investigate whether single nucleotide polymorphisms (SNPs) of TLR7, including rs179009, rs179010 and rs179012, affect the outcomes of HCV infection among the Chinese population. A total of 1767 Chinese Han individuals were enrolled. The distribution of SNP frequencies among three groups with different outcomes of HCV infection was assessed, including healthy controls, cases with spontaneous clearance and cases with viral persistence. Then TLR7 mRNA expression and the production of IFN-α and IL-6 after TLR7 agonist Imiquimod stimulation in vitro were determined. Our results suggested that rs179009 GG genotype was significantly associated with a higher risk of the susceptibility to HCV infection among female subjects (OR=2.42, 95% CI=1.24–4.71, P=0.01). Haplotype GCG was significantly associated with a high risk for HCV susceptibility (OR=1.50, 95% CI=1.11–2.03, P=0.01) as compared with the reference haplotype ACG among females. In the functional research of rs179009, a lower IFN-α level was observed in GG genotype than in AA genotype (P=0.032). Our data indicate that TLR7 rs179009 GG genotype and haplotype GCG were associated with an increased risk of the susceptibility to HCV infection among Chinese females, which may be due to the impaired IFN-α response.

Hepatitis. Chronic HCV infection, diabetes and liver-related outcomes.

There is increasing interest in the role that diabetes has in liver-related outcomes in patients with chronic HCV. Elkrief and colleagues have furthered this discussion by indicating that diabetes may be considered a prognostic factor for major liver-related outcomes in patients with chronic HCV infection, including death and transplantation.

The allele 4 of neck region liver-lymph node-specific ICAM-3-grabbing integrin variant is associated with spontaneous clearance of hepatitis C virus and decrease of viral loads

L-SIGN is a C-type lectin expressed on liver sinusoidal endothelial cells involved in the capture of hepatitis C virus and trans-infection of adjacent hepatocyte cells. The neck region of L-SIGN is highly polymorphic, with three to nine tandem repeats of 23 residues. This polymorphism is associated with a number of infectious diseases, but has not been explored in HCV. We therefore investigated the impact of L-SIGN neck region length variation on the outcome of HCV infection. We studied 322 subjects, 150 patients with persistent HCV infection, 63 individuals with spontaneous clearance and 109 healthy controls. In healthy subjects, we found a total of nine genotypes, with the 7/7 genotype being the most frequent (33%) followed by the 7/6 (22.9%) and the 7/5 (18.3%). The frequencies of the alleles were as follows: 7-LSIGN (56.4%), 6-LSIGN (20.2%), 5-L-SIGN (18.3%) and 4-L-SIGN (5%). The frequency of the 7/4 genotype was higher in spontaneous resolvers (14.3%) as compared with the persistent group (4%) (OR = 0.25, 95% CI = 0.07–0.82, p 0.022). In addition, we found that 4-L-SIGN was associated with spontaneous resolution of HCV infection (OR = 0.30, 95%CI, 0.12–0.74, p 0.005). Interestingly, patients with 4-L-SIGN had lower viral loads when compared with carriers of the 5 (p 0.001), 6 (p 0.021) and 7-alleles (p 0.048). The results indicate that neck region polymorphism of L-SIGN can influence the outcome of HCV infection and the four-tandem repeat is associated with clearance of HCV infection.