Hepatitis C Virus Core Antigen Levels Research Articles

An amino acid substitution in HCV core antigen limits its use as a reliable measure of HCV infection compared with HCV RNA.

Hepatitis C virus (HCV) is a viral pathogen that causes chronic hepatitis, which can lead to cirrhosis and hepatocellular carcinoma. Detection of HCV RNA is the standard method used to diagnose the disease and monitor antiviral treatment. A quantification assay for the HCV core antigen (HCVcAg) has been proposed as a simplified alternative to the HCV RNA test for predicting active HCV infection, with the aim of achieving the global goal of eliminating hepatitis. The objective of this study was to determine the correlation between HCV RNA and HCVcAg, as well as the impact of amino acid sequence heterogeneity on HCVcAg quantification. Our findings demonstrated a strong positive correlation between HCV RNA and HCVcAg across all HCV genotypes (1a, 1b, 3a, and 6), with correlation coefficients ranging from 0.88 to 0.96 (p < 0.001). However, in some cases, samples with genotypes 3a and 6 exhibited lower HCVcAg levels than expected based on the corresponding HCV RNA values. Upon the core amino acid sequence alignment, it was observed that samples exhibiting low core antigen levels had an amino acid substitution at position 49, where threonine was replaced by either alanine or valine. Core mutation at this position may correlate with one of the epitope regions recognized by anti-HCV monoclonal antibodies. The present findings suggest that the utilization of HCVcAg as a standalone marker for HCV RNA might not provide adequate sensitivity for the detection of HCV infection, especially in cases where there are variations in the amino acid sequence of the core region and a low viral load of HCV RNA.

Hepatitis C Virus Core Antigen as an Alternative to RNA in the Assessment of Response to Treatment with Direct-acting Oral Antivirals

Background: Affordable and effective diagnostic and treatment monitoring algorithms are urgently needed to achieve the global elimination of hepatitis C virus (HCV) infection. Methods: A total of 274 patients were treated with direct-acting antivirals (DAAs) in the Spanish Hospital of Albacete between 2004 and 2020. This study compared the enzyme-immunoassay technique for HCV core antigen (HCVcAg) with the determination of RNA of HCV (HCV RNA) by polymerase chain reaction (PCR) in monitoring treatment with DAA, setting the lower limit of detection of HCVcAg &lt; 3 fmol/L and RNA &lt; 10 IU/mL. In all cases, the P value of differences associated with the contrast test was less than or equal to 0.05. Results: We evaluated the viral loads of our patients before treatment, during their treatment, and after its completion. The HCV RNA quantification at diagnosis was 2309327 IU/mL. The mean HCVcAg load was 5972 fmol/L. There was a strong correlation between HCVcAg levels and RNA levels with a Spearman rho of 0.832 (P &lt; 0.01). The HCVcAg sensitivity at diagnosis was 99%, but the specificity could not be calculated because there were no true negatives or false positives at this point. Twelve weeks after treatment, in patients with treatment failure, we obtained a mean of 19084 IU/mL for RNA, while for HCVcAg, the mean was 103 fmol/L. At this time point, we also found a strong correlation between HCVcAg levels and HCV RNA levels with a Spearman rho of 0.775 (P &lt; 0.01). Finally, the virological cure was achieved in 99% of our patients. The results for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 99.87%, 86.33%, and 100%, respectively. Conclusions: HCVcAg determination is an excellent alternative to HCV RNA in the assessment of treatment response. This is particularly relevant in lower- and middle-income countries and resource-limited settings where the high cost of labor, equipment, and reagents can prohibit molecular testing.

Hepatitis C core antigen: a simple predictive marker for treatment response to the new direct-acting antiviral drugs in chronic HCV Egyptian patients

BackgroundSuccessful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new direct-acting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays. Our main objectives were to correlate between serum levels of HCVcAg and HCV RNA loads in chronic HCV patients as well as to explore the potential value of HCVcAg assay in predicting treatment response to the new DAAs. The study enrolled a total of 280 chronic HCV-infected patients scheduled to start the new regimen for treatment of chronic HCV by all-oral, interferon-free DAAs. According to the viral load, the studied individuals were arranged into three groups corresponding to mild, moderate, and sever viremia. Serum level of HCVcAg was determined by ELISA technique and HCV RNA viral loads were quantified using the real-time PCR system. The assays were performed three times for all participants: prior to initiation of treatment, at the end of treatment (week 12), and 3 months post-treatment cessation (week 24).ResultsA statistically significant difference between HCV RNA and HCVcAg baseline levels among different viremia groups was detected (P < 0.001). There was a significant positive correlation between HCV RNA and HCVcAg baseline values among all the studied cases (P < 0.05) with a correlation coefficient of 0.752, 0.976, and 1.00 respectively for mild, moderate, and severe viremia groups. 92.9% (260/280) of the studied patients achieved sustained virologic response, 3.6% (10/280) were non-responders, and 3.6% (10/280) had recurrent viremia/relapse as regards RT-PCR results.ConclusionHCVcAg is a promising alternative to HCV RNA assay. The ELISAs for HCVcAg proved excellent correlations with HCV RNA levels. Moreover, HCVcAg can be introduced as a simple and highly specific tool for monitoring the new DAA regimens particularly in low-resource settings.

Improving Diagnosis of Hepatitis C Virus Infection Using Hepatitis C Core Antigen Testing in a Resource-Poor Setting.

INTRODUCTION: We compared the hepatitis C virus (HCV) core antigen test with the HCV RNA assay to confirm anti-HCV results to determine whether the HCV core antigen test could be used as an alternative confirmatory test to the HCV RNA test. METHODS:Sera from 156 patients were analyzed for anti-HCV and HCV core antigen using a chemiluminescent microparticle immunoassay (Architect i2000SR) and for HCV RNA using the artus HCV RG RT-PCR Kit (QIAGEN) in a Rotor-Gene Q instrument. RESULTS: The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 77.35%, 100%, 100%, and 89.38%, respectively. HCV core antigen levels showed a good correlation with those from HCV RNA quantification (r =0.872). However, 13 samples with a viral load of less than 4000 IU/mL were negative in the HCV core antigen assay. All gray-zone reactive samples were also RNA positive and were positive on repeat testing.CONCLUSIONS: The Architect HCV core antigen assay is highly specific and has an excellent positive predictive value. At the present level of sensitivity (77%), the study is still relevant in a low-income setting in which most of the HCV-positive patients would go undiagnosed, since HCV RNA testing is not available and/or not affordable. HCV core antigen testing can also help determine the true burden of infection in a population, considering the fact that almost 50% of the anti-HCV positive cases are negative for HCV RNA.

Clinical Utility of Enzyme-Linked Immunosorbent Assay for Hepatitis C Core Antigen Quantification in Diagnosis and Monitoring Patients Treated with Direct-Acting Antivirals in A Resource Limited Setting

Background: Hepatitis C virus core antigen (HCV-cAg) assay has been proposed as a more economical alternative to HCV RNA detection. Aim of the work: To evaluate the clinical utility of ELISA for HCV-cAg quantification in diagnosis and monitoring treatment outcomes in patients treated with direct acting antivirals (DAAs) for chronic hepatitis C. Patients and Methods: A prospective study on 40 subjects recruited from hepatology department and outpatient clinic in Ain Shams University Hospitals. Group I included 20 patients with positive anti-HCV antibody. Group II included 20 healthy subjects. The patient group received a combination of sofosbuvir 400 mg and daclatasvir 60 mg once daily for 12 weeks. The levels for both HCV-cAg and HCV RNA were evaluated at baseline and 12 weeks after completion of therapy. Results: Baseline HCV-cAg levels showed good correlation with HCV viral load (r=0.808, p 8 IU/ml. Conclusion: ELISA for HCV-cAg can replace the high sensitivity HCV RNA molecular assay to confirm the presence of HCV infection and to monitor treatment outcome.

Clinical Utility of Enzyme-Linked Immunosorbent Assay for Hepatitis C Core Antigen Quantification in Diagnosis and Monitoring Patients Treated with Direct-Acting Antivirals in A Resource Limited Setting

Background: Hepatitis C virus core antigen (HCV-cAg) assay has been proposed as a more economical alternative to HCV RNA detection. Aim of the work: To evaluate the clinical utility of ELISA for HCV-cAg quantification in diagnosis and monitoring treatment outcomes in patients treated with direct acting antivirals (DAAs) for chronic hepatitis C. Patients and Methods: A prospective study on 40 subjects recruited from hepatology department and outpatient clinic in Ain Shams University Hospitals. Group I included 20 patients with positive anti-HCV antibody. Group II included 20 healthy subjects. The patient group received a combination of sofosbuvir 400 mg and daclatasvir 60 mg once daily for 12 weeks. The levels for both HCV-cAg and HCV RNA were evaluated at baseline and 12 weeks after completion of therapy. Results: Baseline HCV-cAg levels showed good correlation with HCV viral load (r=0.808, p 8 IU/ml. Conclusion: ELISA for HCV-cAg can replace the high sensitivity HCV RNA molecular assay to confirm the presence of HCV infection and to monitor treatment outcome.

Vitamin D derivatives inhibit hepatitis C virus production through the suppression of apolipoprotein

Supplementation with vitamin D (VD) has been reported to improve the efficacy of interferon-based therapy for chronic hepatitis C. We found that 25-hydroxyvitamin D3 (25-(OH)D3), one of the metabolites of VD, has antiviral effects by inhibiting the infectious virus production of the hepatitis C virus (HCV). In this study, to clarify the underlying mechanisms of the anti-HCV effects, we searched VD derivatives that have anti-HCV effects and identified the common target molecule in the HCV life cycle by using an HCV cell culture system. After infection of Huh-7.5.1 cells with cell culture-generated HCV, VD derivatives were added to culture media, and the propagation of HCV was assessed by measuring the HCV core antigen levels in culture media and cell lysates. To determine the step in the HCV life cycle affected by these compounds, the single-cycle virus production assay was used with a CD81-negative cell line. Of the 14 structural derivatives of VD, an anti-HCV effect was detected in 9 compounds. Cell viability was not affected by these effective compounds. The 2 representative VD derivatives inhibited the infectious virus production in the single-cycle virus production assay. Treatment with these compounds and 25-(OH)D3 suppressed the expression of apolipoprotein A1 and C3, which are known to be involved in infectious virus production of HCV, and the knockdown of these apolipoproteins reduced infectious virus production. In conclusion, we identified several compounds with anti-HCV activity by screening VD derivatives. These compounds reduce the infectious virus production of HCV by suppressing the expression of apolipoproteins in host cells.

Evaluation of a Hepatitis C Virus Core Antigen Assay in Plasma and Dried Blood Spot Samples

Simplified, affordable tools to diagnose active hepatitis C virus (HCV) infection are needed to scale up treatment. This study evaluated the analytical performance of HCV core antigen (HCVcAg) detection in samples of plasma and dried venous blood spots (DBSs). Paired plasma and DBS samples were prepared from remnant diagnostic samples, and plasma HCV RNA and HCVcAg were quantified. Sensitivity and specificity for HCVcAg (>3 fmol/L) at two HCV RNA thresholds (≥15 and ≥3000 IU/mL) were calculated. Of 120 paired samples tested, 25 had nonquantifiable HCV RNA and 95 had quantifiable HCV RNA. The median HCV RNA level in plasma was 5.6 log10 IU/mL (interquartile range: 5.2 to 6.2). The median HCVcAg levels in plasma and DBS samples were 2.3 log10 fmol/L (interquartile range: 0.1 to 3.1) and 1.1log10 fmol/L (interquartile range: 0.0 to 1.9), respectively. For diagnosing HCV RNA ≥3000 IU/mL, the sensitivity and specificity of HCVcAg in plasma were 97.7% (95% CI, 91%-100%) and 100% (95% CI, 87%-100%), respectively. The sensitivity and specificity of HCVcAg in DBS were 88.6% (95% CI, 80%-94%) and 97% (95% CI, 82%-100%), respectively. The data from this study demonstrate good sensitivity and specificity of HCVcAg inplasma at an HCV RNA threshold of ≥3000 IU/mL. The level of HCVcAg quantified in plasma was higher than that in DBS.

Evaluation Of An Enzyme Immunoassay For Hepatitis C Virus Core Antigen As A Diagnostic Test For Detection Of Hepatitis C Virus Infection In Comparison To Real-Time RT-PCR

Hepatitis C virus (HCV) is a global public health care problem. Diagnosis of HCV infection was mainly based on the detection of anti-HCV antibodies as a screening test with serum samples and detection of HCV RNA by using RT-PCR, which considered as a golden standard test. In this study, we compared the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from 100 patients were analyzed for anti-HCV and HCV core antigen both with the ELISA and with the molecular HCV RNA assay consisting of a real time-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 76.1%, 86.2%, 80%, and 82.5%, respectively. The HCV core antigen levels showed a poor correlation with those from the HCV RNA quantification (r = 0.321, p= 0.079). In conclusion, the core antigen detection test can be more valuable in HCV diagnosis than anti-HCV antibodies but it cannot replace HCV RNA in confirmation of the diagnosis of HCV because the sensitivity of the HCV core antigen detection assay is significantly lower than that of PCR-based methods.

HEPATITIS C VIRUS (HCV) CORE ANTIGEN AS AN ALTERNATIVE TO PCR FOR HCV, RNA QUANTIFICATION TO EARLY DIAGNOSIS OF HCV INFECTION AMONG BLOOD DONORS

Background: Safety blood transfusion is based on reliable donor screening for transmissible infections such as the hepatitis C virus (HCV) infection. HCV-RNA by polymerase chain reaction (PCR) test is a gold standard test for HCV infection but with three major limitations: liability of RNA molecules, higher costs, and longer turnaround time as compared with HCV core antigen (HCVcAg) testing. Objective: To evaluate HCV core Ag as an alternative to PCR for HCV RNA to early diagnosis of HCV infection among blood donors. Patients and Methods: 4222 blood donors collected between March 2015 and July 2016 at Blood Bank Center of Najran Hospitals, Southwestern Saudia Arabia. Anti-HCV, HBsAg, syphilis and HIV were screened by third generation ELISA. Those reactive to HbsAg, syphilis and/or HIV were excluded. HCV core Ag and HCV RNA by RT-PCR were performed on 76 positive HCV-Ab sera. Results: Among total 4222 blood donors (3837 males (90.88%) and 385 females (9.12%)), 76 (1.8%) were positive for HCV-Ab (72 males; 94.74% and 4 females; 5.26%). HCV core Ag was ≥ 11 fmol/L in 65 cases (85.53%) of HCV Ab positive patients (61 males; 93.85% and 4 females; 6.15%), 3 cases with HCVcAg levels in grey zone (3-11 fmol/L) and 8 cases with HCVcAg ≤ 3 fmol/L all of both were males. HCV RNA was detected in 71/76 (93.42%) of donors with positive HCV-Ab and in 3 of 8 (37.5%) of those with positive HCV-ab and negative HCVcAg. HCVcAg has sensitivity, specificity, PPV and NPV of 97.14, 100, 100 and 99.76 values respectively at a cutoff 2.82 fmol/L compared to HCV RNA test. Conclusion: Higher sensitivity and specificity of HCVcAg with rapid turn around time of the results, and its lower price suggested that can be used alternatively to HCV RNA test in early diagnosis of HCV infection.

Low-Dose Pegylated Interferon α-2b Plus Ribavirin for Elderly and/or Cirrhotic Patients with Genotype 2 Hepatitis C Virus.

Background/AimsThis study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks.MethodsLow-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured.ResultsThe patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively.ConclusionsLow-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

The Correlation between Hepatitis C Core Antigen and Hepatitis C Virus RNA Levels with Respect to Human Immunodeficiency Virus Status, Hepatitis C Virus Genotype and Interferon-Lambda-4 Polymorphism

Objectives: Serum hepatitis C virus (HCV) core antigen (HCVcAg) concentrations correlate with HCV RNA levels in HCV monoinfected patients. Data in HCV/HIV coinfected patients are still limited. We aim to compare the use of HCVcAg measurement with respect to HIV status, HCV genotypes, interferon-lambda-4 (IFNL4) polymorphism and clinical parameters. Methods: We analyzed an untreated cohort of 104 patients with HCV monoinfection and 85 patients with HCV/HIV coinfection. Serum HCVcAg was measured by a commercial chemiluminescent microparticle immunoassay. The presence of IFNL4 polymorphism ss469415590 was identified by real-time PCR. Results: log₁₀ HCVcAg levels were significantly correlated with corresponding log₁₀ HCV RNA levels (r = 0.889, p < 0.001), but not with ALT levels and liver stiffness. The correlation between HCV RNA and HCVcAg was particularly high in coinfected patients and those with high viremia. Mean log₁₀ HCVcAg concentration was significantly higher in coinfected patients than in monoinfected patients. Patients harboring the TT/TT genotype of ss469415590 had significantly higher levels of log₁₀ HCVcAg than those with the non-TT/TT genotype. HCVcAg levels were similar across HCV genotypes. Conclusions: HCVcAg concentrations had an excellent correlation with HCV RNA levels, particularly in HCV/HIV-coinfected individuals and might be associated with IFNL4 polymorphism. HCVcAg testing could be used as an alternative to HCV RNA assays in resource-limited settings.

Impact of a single nucleotide polymorphism upstream of the IL28B gene in patients positive for anti-HCV antibody in an HCV hyperendemic area in Japan.

The influence of genetic variation at the interleukin-28B (IL28B) locus on the natural course of hepatitis C virus (HCV) infection has not been fully investigated. The goal of this study was to examine whether an IL28B polymorphism (rs8099917) is associated with natural clearance of HCV and with disease parameters of HCV infection in an HCV hyperendemic area of Japan. The patients were 502 anti-HCV antibody-positive residents who participated in liver disease screening program from 2002 to 2004. Patients who underwent interferon-based therapy or had hepatocellular carcinoma were excluded. Of these patients, 149 were negative for HCV RNA (prior infection) and 353 were positive for HCV RNA or HCV core antigen (HCV carriers). In multivariate analysis, the IL28B TT genotype was a predictor for prior HCV infection. In addition, nine of the patients with prior HCV infection were positive for anti-HCV antibody with positive for HCV core antigen or HCV RNA before 2001, and these nine patients all had the IL28B TT genotype. Furthermore, the IL28B TT genotype was associated independently with higher HCV core antigen levels in HCV carriers. In contrast, the IL28B genotype did not affect the biochemical markers, such as alanine aminotransferase, hepatic fibrosis markers, and α-fetoprotein, and the degree of hepatic fibrosis assessed by transient elastography in HCV carriers. We concluded that IL28B polymorphism (TT genotype) is associated with spontaneous clearance of HCV and conversely with high viral loads in HCV carriers. In contrast, the IL28B genotype does not affect disease progression such as hepatic fibrosis.

Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C

BackgroundHepatitis C virus (HCV) core antigen has been proposed as a surrogate marker of HCV replication. HCV core antigen detection and quantification can thus theoretically be used instead of nucleic acid testing (NAT) to diagnose infection and manage antiviral therapy, with several advantages compared to HCV RNA assays. HCV core antigen can now be easily detected and quantified by means of a chemiluminescent microparticle immunoassay on the Abbott Architect device. ObjectiveThe aim of the present study was to evaluate the clinical performance of the Architect HCV Ag assay for the detection and quantification of HCV core antigen in patients with chronic HCV genotype 1–6 infections. ResultsThe Architect HCV Ag assay had a specificity of 100% (95%CI: 97.8–100%). HCV core antigen levels were not influenced by the HCV genotype. The lower limit of detection of 3fmol/L corresponded to approximately 1000IU/mL of HCV RNA, regardless of the real-time PCR assay used. HCV core antigen and HCV RNA levels correlated for HCV genotype 1–4 (r=0.89 and r=0.88 for the m2000 and the CAP/CTM v2.0 assay, respectively). ConclusionsThe Architect HCV Ag assay is highly specific and easy to perform. It represents a valuable screening, diagnostic and monitoring tool, especially in the era of new all-oral, interferon-free antiviral strategies that do not require high analytical sensitivity.

Hepatitis C virus core antigen, an earlier and stronger predictor on sustained virological response in patients with genotype 1 HCV infection

BackgroundEarlier kinetics of serum HCV core antigen (HCVcAg) and its predictive value on sustained virological response (SVR) were investigated in patients with genotype 1 HCV infection during antiviral treatment.MethodsIn a multi-centered, randomized and positive drug-controlled phase IIb clinical trial on type Y peginterferon α-2b ( NCT01140997), forty-eight CHC patients who participated in pharmacokinetics were randomly divided into 4 cohorts and treated with PegIFNα (type Y peginterferon α-2b 90 μg, 135 μg, 180 μg and PegIFNα-2a 180 μg, respectively, once a week) and ribavirin (< 75 kg, 1000 mg daily and ≥ 75 kg, 1200 mg daily) for 48 weeks, and then followed up for 24 weeks. 32 patients infected with genotype 1 HCV and completed the whole process were included in this study. HCV RNAs were detected at baseline, and weeks 4, 12, 24, 48 and 72 using Cobas TaqMan. ARCHITECT HCVcAg was performed at 24, 48, 72, 96, 120 and 144 h in addition to the above time points. The receiver operating curves (ROCs) were performed to study the predictive values of HCVcAg decline on SVR.ResultsFollowing antiviral treatment, serum HCVcAg levels rapidly declined within the first week and correlated well with corresponding HCV RNA at baseline, weeks 4, 12, 24, 48 and 72 (rs = 0.969, 0.928, 0.999, 0.983, 0.985 and 0.946, respectively, P < 0.001). All of the areas under the receiver operating curves (AUROCs) were more than 0.80 and showed good predictive power on SVR at 24, 48, 72, 96, 120 and 144 h. The144 h was the best predictive time point of HCVcAg decline on SVR because of its largest AUROC (more than 0.90).ConclusionsEarly kinetics of serum HCVcAg predicts SVR very well in genotype 1 CHC patients during antiviral treatment, and its reduction value at 144 h is an earlier and stronger predictor on SVR than rapid virological response and early virological response. (TRN: NCT01140997).

An unbalanced PD-L1/CD86 ratio in CD14++CD16+ monocytes is correlated with HCV viremia during chronic HCV infection

Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus (HCV) infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets-CD14(++)CD16(-), CD14(++)CD16(+) and CD14(+/dim)CD16(+)-in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD14(++)CD16(+) monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14(++)CD16(+) monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor (TLR) ligand binding and HCV JFH-1stimulation. These findings indicates the compromised immune status of the CD14(++)CD16(+) monocytes during chronic HCV infection and provides new insights into the specific role of the CD14(++)CD16(+) monocytes and their significance in chronic HCV infection.

C 型肝炎地域流行既往者の長期追跡成績

We examined the natural course and clinical characteristics of 138 HCV carriers according to HCV genotypes. Stored serum samples obtained from patients were examined for HCV core antigen levels and HCV genotypes. Genotype 1b was found in 79 (57.2%), genotype 2a in 8 (5.8%), genotype 2b in 46 (33.3%) and genotype 1b+2b in 5 (3.6%) patients.119 patients followed 20 years or more after infection excluding genotype 1b+2b were classified into two groups : genotype 1b and non-genotype 1b (2a and 2b : 2a/2b). The numbers of patients were 70 and 49 in the genotype 1b and genotype 2a/2b groups, respectively. Patients with genotype 2a/2b had significantly higher HCV core antigen levels 20 years after infection than those with genotype 1b. However, patients with genotype 1b had significantly higher ZTT and type IV collagen than those with genotype 2a/2b.HCV core antigen levels in cases with genotype 1b did not increase 10 years or more after infection ; on the other hand, those with genotype 2a/2b increased significantly.

English

Quantitative tests for the detection of hepatitis C virus ribonucleic acid (HCV-RNA) levels and HCV core antigen have been mainly used for the management of patients with HCV infection. The aim of this study was to evaluate the correlation between HCV core antigen and HCV RNA levels in patients reactive for anti-HCV antibodies. Three hundred and twenty-five anti-HCV reactive sera samples were included in the study. HCV core antigen and HCV RNA levels were determined using the Architect HCV Ag test and Abbott RealTimeTM HCV RNA test (RT-PCR), respectively. The correlation coefficient between the levels of HCV core antigen and HCV RNA test results was calculated using Spearman&rsquo;s rank test, and linear regression analysis was applied. One hundred and sixteen of the 325 samples were detected positive by both methods. Three additional samples by RT-PCR, and 4 samples by Architect HCV Ag, the negative samples were found positive by the other method. All of these contradictory results were obtained from the low level HCV RNA or HCV core antigen including samples. A correlation coefficient (r) was determined as 0.899 between the levels of HCV core antigen and HCV RNA (p&lt;0.0001). The sensitivity, specificity, positive predictive value and negative predictive value of the HCV core antigen test were 97.48, 98.06, 96.67 and 98.54%, respectively, using the HCV RNA test as a reference. The Architect HCV core antigen test exhibits a good correlation with the HCV RNA test. It can be used as an alternative method, especially when the HCV RNA test is unavailable. &nbsp; Key words: Anti- hepatitis C virus, Architect hepatitis C virus Ag test, hepatitis C virus RNA.

Prediction of efficacy to pegylated interferon‐α‐2b plus ribavirin in patients with genotype 2 hepatitis C virus using viral response within 2 weeks

Rapid virological response (RVR), defined as serum hepatitis C virus (HCV) RNA negativity at 4 weeks, is the most useful predictor of sustained virological response (SVR) to standard pegylated interferon (PEG IFN) plus ribavirin therapy for patients infected with genotype 2 HCV. The aim of the present study was to predict SVR using viral response within 2 weeks of therapy initiation. Of 64 HCV genotype 2 patients with a high viral load treated with standard PEG IFN-α-2b plus weight-based ribavirin for 24 weeks, 58 patients whose adherence was more than 67% were analyzed. RNA and core antigen levels were measured at four time points: the day of therapy initiation, the following day, and at 1 and 2 weeks. SVR was achieved in 73% (47/64) of patients. Univariate analysis of SVR contributing factors showed significant differences with age, bodyweight, white blood cell count, platelet count, fibrosis marker levels, baseline core antigen level and viral response. The area under the receiver-operator curve (AUC) of the core antigen level at 1 week (AUC, 0.940) was the highest among the significant SVR predicting factors. Setting 100 fmol/L as the cut-off value for core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for predicting SVR were 100%, 86%, 96%, 100% and 97%, respectively, and for predicting RVR were 66%, 93%, 97%, 46% and 72%, respectively. The HCV core antigen level at 1 week after therapy initiation is the most useful predictor for SVR.

25-hydroxyvitamin D3suppresses hepatitis C virus production

Because the current interferon (IFN)-based treatment for hepatitis C virus (HCV) infection has a therapeutic limitation and side effects, a more efficient therapeutic strategy is desired. Recent studies show that supplementation of vitamin D significantly improves sustained viral response via IFN-based therapy. However, mechanisms and an active molecular form of vitamin D for its anti-HCV effects have not been fully clarified. To address these questions, we infected HuH-7 cells with cell culture-generated HCV in the presence or absence of vitamin D(3) or its metabolites. To our surprise, 25-hydroxyvitamin D(3) [25(OH)D(3) ], but not vitamin D(3) or 1,25-dihydroxyvitamin D(3) , reduced the extra- and intracellular levels of HCV core antigen in a concentration-dependent manner. Single-cycle virus production assay with a CD81-negative cell line reveals that the inhibitory effect of 25(OH)D(3) is at the level of infectious virus assembly but not entry or replication. Long-term 25(OH)D(3) treatment generates a HCV mutant with acquired resistance to 25(OH)D(3) , and this mutation resulting in a N1279Y substitution in the nonstructural region 3 helicase domain is responsible for the resistance. 25(OH)D(3) is a novel anti-HCV agent that targets an infectious viral particle assembly step. This finding provides insight into the improved efficacy of anti-HCV treatment via the combination of vitamin D(3) and IFN. Our results also suggest that 25(OH)D(3) , not vitamin D(3) , is a better therapeutic option in patients with hepatic dysfunction and reduced enzymatic activity for generation of 25(OH)D(3) .