Effect of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis.

This study aimed to explore the role of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis (CM).Patients were assigned into 4 groups (n = 40/group): group A (HIV/AIDS with CM), group B (HIV/AIDS with tuberculosis), group C (HIV/AIDS), and group D (CM). The levels of IL-10 and associated indicators were measured and the correlations were analyzed by Pearson correlation and partial correlation method. In plasma and cerebrospinal fluid (CSF), no significant difference was observed on IL-10 level between group A and other groups (P > 0.050). R values for IL-10 and relevant indicators in blood were as follows (P < 0.050): group A, IFN-γ (-0.377), IL-12 (0.743), IL-4 (0.881), and IL-6 (0.843); group B, IL-12 (0.740), IL-4 (0.573), and IL-6 (0.900); group C, IL-12 (0.402) and IL-4 (0.896); group D, IL-12 (0.575), IL-4 (0.852), and CD8 (0.325). R values for IL-10 and related indicators in CSF were as follows (P < 0.050): group A, TNF-α (0.664), IL-4 (0.852), white blood cells (WBCs, 0.321) and total protein (TP, 0.330); group B, TNF-α (0.566), IL-4 (0.702), and lactate dehydrogenase (LDH, 0.382); group D, IFN-γ (0.807) and IL-4 (0.441). IL-10 level was positively correlated with IL-4, IL-6, IL-12, TNF-α, WBC, and TP in blood or CSF, and negatively correlated with IFN-γ in blood, suggesting that IL-10 affected both pro-inflammatory and anti-inflammatory activities in the pathogenesis of HIV/AIDS with CM.

Causal relationships between metabolic-associated fatty liver disease and iron status: Two-sample Mendelian randomization.

BACKGROUND & AIMS: Dysregulated iron homeostasis plays an important role in the hepatic manifestation of metabolic-associated fatty liver disease (MAFLD). We investigated the causal effects of five iron metabolism markers, regular iron supplementation and MAFLD risk. METHODS: Genetic summary statistics were obtained from open genome-wide association study databases. Two-sample bidirectional Mendelian randomization analysis was performed to estimate the causal effect between iron status and MAFLD, including Mendelian randomization inverse-variance weighted, weighted median methods and Mendelian randomization-Egger regression. The Mendelian randomization-PRESSO outlier test, Cochran's Q test and Mendelian randomization-Egger regression were used to assess outliers, heterogeneity and pleiotropy respectively. RESULTS: Mendelian randomization inverse-variance weighted results showed that the genetically predicted per standard deviation increase in liver iron (Data set 2: odds ratio 1.193, 95% confidence interval [CI] 1.074-1.326, p = .001) was associated with an increased MAFLD risk, consistent with the weighted median estimates and Mendelian randomization-Egger regression, although Data set 1 was not significant. Mendelian randomization inverse-variance weighted analysis showed that genetically predicted MAFLD was significantly associated with increased serum ferritin levels in both datasets (Dataset 1: ß = .038, 95% CI = .014 to .062, p = .002; Dataset 2: ß = .081, 95% CI = .025 to .136, p = .004), and a similar result was observed with the weighted median methods for Dataset 2 instead of Mendelian randomization-Egger regression. CONCLUSIONS: This study uncovered genetically predicted causal associations between iron metabolism status and MAFLD. These findings underscore the need for improved guidelines for managing MAFLD risk by emphasizing hepatic iron levels as a risk factor and ferritin levels as a prognostic factor.

An enlightening role for cytokine storm in coronavirus infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).

Diagnostic role of CXCL13 and CSF serology in patients with neurosyphilis.

BACKGROUND: Considering the unknown prevalence of neurosyphilis in West China, and the confusing diagnosis of neurosyphilis, the role of CSF_CXCL13 and syphilis serology was studied to provide a more accurate reference for the clinical detection and diagnosis of neurosyphilis. METHODS: A retrospective data set I was used to investigate the prevalence of neurosyphilis, as well as the laboratory characteristics of 244 patients. Besides, to explore the diagnostic value of CSF_CXCL13 and syphilis serology for neurosyphilis, another 116 CSF_serum paired samples (data set II) were collected from 44 neurosyphilis and 72 non-neurosyphilis/syphilis patients. RESULTS: About 6.25% (156 out of 2494) syphilis was neurosyphilis. When Treponema pallidum infection occurs, syphilis serology (sero_TRUST ≥1:16 and sero_TPPA titre ≥1:10240) can be good predictors of neurosyphilis, as well as syphilis CSF serology (CSF_TPPA ≥1:320, CSF_TRUST and venereal disease research laboratory). The sensitivity of serology in neurosyphilis can be complemented by CSF_CXCL13, which could be the therapy monitor of neurosyphilis. CONCLUSION: Due to the lack of ideal biomarkers for neurosyphilis, the importance of syphilis serology cannot be ignored, and their combination with CSF_CXCL13 or other biomarkers should be further investigated.

Pyrotinib in vitro metabolite profiling via rat, dog and human hepatocytes using liquid chromatography-quadrupole/orbitrap mass spectrometry.

RATIONALE: Pyrotinib is an irreversible EGFR/HER2 inhibitor that has shown antitumor activity and tolerance in the treatment of breast cancer. Studies focused on its metabolic pathways and major metabolites are insufficient. In the evaluation of drug safety and therapeutic use, metabolite characterization is critical. The metabolism of pyrotinib in vitro was studied utilizing rat, dog and human hepatocytes in this study. METHODS: Pyrotinib (10 µM) was incubated with hepatocytes in Williams' E medium. The metabolites were examined and profiled using ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry. The metabolite structures were deduced by comparing their precise molecular weights, fragment ions and retention times with those of the parent drug. RESULTS: A total of 16 metabolites, including 6 novel ones, were discovered and structurally described under the present conditions. Oxidation, demethylation, dehydrogenation, O-dealkylation and glutathione (GSH) conjugation were all involved in the metabolism of pyrotinib in hepatocytes. The most predominant metabolic route was identified as GSH conjugation (M5). CONCLUSIONS: This study generated valuable metabolite profiles of pyrotinib in several species, which will aid in the understanding of the drug's disposition in various species and in evaluating the contribution of metabolites to overall effectiveness and toxicity of pyrotinib.

Fluorescence and visual immunoassay of HIV-1 p24 antigen in clinical samples via multiple selective recognitions of CdTe QDs.

Human immunodeficiency virus (HIV) infection inflicts significant economic and social burdens on many countries worldwide. Given the substantial morbidity and mortality from HIV infection, there is an urgent need for accurate and early detection of the virus. In this study, immunofluorescence and visual techniques are described that detect the HIV-1 p24 antigen, which relied on selective recognition of Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+ using cadmium telluride quantum dots (CdTe QDs). After the sandwich immunoreactions were accomplished, the alkaline phosphatase (ALP) hydrolyzed L-ascorbic acid 2-phosphate (AAP) to form ascorbic acid (AA) that further reduces Ag+ and Cu2+ to Ag NPs and Cu+, respectively. This method was highly sensitive and selective and could detect as low as 1 pg/mL of p24 antigen by naked eyes and had a good linearity in the concentration range 1-100 pg/mL. When using Ag+ and Cu2+ as media, the limit of detection (LOD) of the new method was 0.3 pg/mL and 0.2 pg/mL, respectively. Compared with clinical electrochemiluminescence immunoassay (ECLIA) results and clinical data, this method demonstrated good consistency for the quantification of HIV-1 p24 antigen in 34 clinical serum samples. In addition, this method could accurately distinguish HIV from other viruses and infections such as hepatitis B virus, systemic lupus erythematosus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, lipemia, and hemolysis. Therefore, our dual-mode analysis method may provide additional solutions to identify clinical HIV infection. An immunofluorescence and visualization dual-mode strategy for the detection of p24 antigen was constructed based on immune recognition reaction and a phenomenon that cadmium telluride quantum dots (CdTe QDs) can selectively recognize Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+.

Acute HIV infection in a large teaching hospital in western China: Clinical, virological, and molecular epidemiological characteristics.

OBJECTIVE: To provide information on clinical, virological, and molecular epidemiological characteristics for early identification, diagnosis, and treatment of acute HIV infection (AHI). METHODS: A retrospective study was conducted with patients with AHI from 2012 to 2017 in West China Hospital. RESULTS: A total of 47 patients with AHI were found using a fourth-generation kit. Thirteen (27.66%) of these patients were negative if tested by third-generation tests. Median age of patients with AHI was 26 and 91.49% of them were males. Homosexual contact was responsible for 46.81% of AHI transmission. Among the individuals with AHI, 80.85% were outpatients. Common symptoms/signs were fever, headache, rash, cough and sputum, and sore throat. The syphilis coinfection rate was 17.24%. Most of the AHI was distributed in Fiebig stages IV (61.70%) and II (27.66%) with different clinical and virological characteristics. The increasing trend of cut-off index values was obvious in the course of AHI, helpful for auxiliary diagnosis. The main genetic forms of AHI were CRF07_BC and CRF01_AE, and a rare subtype CRF55_01B in Sichuan province was found. The drug resistance mutation rate was relatively high (17.65%) and five different mutations were identified. CONCLUSIONS: Fourth-generation assays are strongly recommended for screening AHI compared to third-generation ones. Different clinical and virological characteristics in different Fiebig stages were found. Young individuals and outpatients were the majority of patients with AHI and this deserves special attention. Attention should also be paid to the rare CRF55_01B in Sichuan province and surveillance of HIV resistance ought to be strengthened.

Epidemiological, clinical characteristics and drug resistance situation of culture-confirmed children TBM in southwest of China: a 6-year retrospective study.

BACKGROUND: Sichuan is a province located in southwestern China, which have a higher incidence of tuberculosis (TB). This study aimed to analyze the epidemiological and clinical characteristics, as well as drug resistance in culture-confirmed children with Tuberculosis meningitis (TBM) in Southwest of China. METHODS: We performed a retrospective study on children (< 14 years old) with cerebrospinal fluid (CSF) culture-confirmed TBM between January 2013 and December 2018 at Public Health Clinical Center of Chengdu (PHCCC). Mycobacterium tuberculosis (MTB) drug sensitivity testing (DST) was performed using the MicroDST™ method. The age, gender, family history of tuberculosis, status of Bacillus Calmette-Guérin (BCG) vaccination, residential areas information, clinical, laboratory, and radiological features were recorded. Data were analyzed using SPSS Statistics Client 25.0, and the change in drug resistance rate was examined using the Cruskal-Wallis test. RESULTS: Among 319 patients clinically diagnosed with TBM, 42 (13.2%) were Mycobacterial culture positive. Their median age was nine years, and the distribution was equal among female and male patients. Among 42 patients who were enrolled in the study, 1/42 (2.38%) passed away. Children with TBM were concentrated in the minority areas of western Sichuan, where 34/42 (81.0%) patients with TBM belonged to ethnic minorities, and only 2/42 (4.76%) received BCG vaccination in the past. Chest X-rays changes were observed in all patients. Fever and headache were the most common presenting symptom. Thirty-five (83.3%) patients suffered from neck stiffness, and 30/42 (71.4%) had high CSF pressure. DST results showed that the resistance rate was high; resistance to any anti-tuberculosis drug (ATD) was observed in 13 (31.0%) patient isolates, while multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were found in 2 (4.8%) and 1 (2.4%) patients, respectively. CONCLUSIONS: TBM among children in Southwest China was mainly concentrated in the minority areas of western Sichuan and more than 95% of patients did not receive BCG vaccination at birth. The most common symptoms were fever, headache, and neck stiffness and all patients had positive chest X-ray findings. In addition, high rates of drug resistance were found.

The evaluation of low cut-off index values of Elecsys® HIV combi PT assay in predicting false-positive results.

OBJECTIVE: To analyze the results of different cut-off index (COI) values of Elecsys® HIV combi PT assay and to assess the role of COI in reducing the frequency of false-positive results. METHODS: We conducted a retrospective study of samples analyzed by Elecsys® HIV combi PT assay, a 4th-generation ECLIA, between 2016 and 2017. A total amount of 379 122 samples were collected for HIV (Human Immunodeficiency Virus) screening. RESULTS: A total of 379 122 samples were analyzed. 2528 (0.67%) were positive by Elecsys® HIV combi PT. Of these, 468 were false-positive results, and most of them (94.87%) were in samples with 1 < COI < 15. The false-positive rate was 0.12%. Patients with false-positive samples were more distributed in elder (P < .001) and female (P < .001) than true-positive specimens. The median COI in true-positive specimens was (385.20), which is significantly higher than false-positive specimens (2.08). The consistency between Elecsys® HIV combi PT assay and 3rd-generation and positive predictive value (PPV) increased with higher COI values. Cancer, infection, and neurological diseases were considered the potential confounding factors of HIV false-positive results (19.44%, 11.11%, and 6.62%, respectively). CONCLUSION: Samples with low COI values, especially those contain confounding factors, need to be further scrutinized to determine whether the confounding factors may cause false-positive problem. In addition, the hypothesis that low COI values may predict false-positive results is valid.

Gender-dependent pharmacokinetics of olaparib in rats determined by ultra-high performance liquid chromatography/electrospray ionization tandem mass spectrometry.

The aim of the present study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method for the determination of olaparib in rat plasma. The plasma samples were processed using one-step protein precipitation with acetonitrile and then separated on Waters Acquity BEH C18 column (50 × 2.1 mm, particle size 1.7 µm) using water containing 0.1% formic acid and acetonitrile as mobile phase with optimized gradient elution. Mass spectrometric detection was carried out by selective reaction monitoring mode via positive ESI mode with precursor-to-product transitions of m/z 435.3 > 367.1 and m/z 443.1 > 375.2 for olaparib and 2 H8 -olaparib (internal standard). The method was linear over the concentration range 0.1-2000 ng/ml with correlation coefficient >0.9987. The lower limit of quantitation was 0.1 ng/ml. The method showed excellent accuracy and precision, negligible matrix effect and high extraction recovery. The validated method was subsequently utilized to determine the concentration of olaparib in rat plasma and further applied to the pharmacokinetic study of olaparib in rat plasma. Our results demonstrated that olaparib showed gender-dependent pharmacokinetics in rats. Compared with that in males, olaparib showed high plasma exposure, long half-life, low clearance and high bioavailability in females.

Molecular Evolution of Clinical Pathogenic Streptococci.

The genus Streptococcus comprises a wide variety of pathogenic and commensal gram-positive bacteria, many of which the pathogenic species cause severe, invasive infections that account for a high burden of morbidity and mortality. Here, we reviewed the evolution of representative virulence factors, capsule in Streptococcus pneumoniae, M protein in Streptococcus pyogenes (GAS), biofilm in Streptococcus agalactiae (GBS) and some oral Streptococcus, as well as the effect caused by evolution, antibiotic resistance and vaccine escape. Thanks to the rapid development of whole genome sequence (WGS) data, the impact of genetic recombination to the Streptococcus evolution has been proved. As to adaptive evolution caused by antibiotics, vaccine and so on, continuous surveillance is an essential to monitor evolution of Streptococcus causing disease. This knowledge is invaluable to the development of preventative and control strategies against this important pathogen.

Long noncoding RNA GAS5 does not regulate HBV replication.

Hepatitis B virus (HBV) infection remains a severe health burden worldwide. Emerging long noncoding RNAs (lncRNAs) are hijacked to enhance virus replication or employed by the host to stimulate immune responses to clear the virus. LncRNA growth arrest-specific transcript 5 (GAS5) can regulate RNA virus by suppressing the replication of both hepatitis C virus and human immunodeficiency virus. In this study, we explored the changes of HBV replication by overexpressing or knocking down GAS5 in HepAD38 cell and HepG2 cell transfected with pHBV1.2. We found HBV can induce the expression of GAS5. However, GAS5 had no effect on extracellular HBsAg and HBeAg, nor intracellular HBV RNA and HBV DNA. In addition, GAS5 possessed similar expression levels between stable HBV-producing cell lines and hepatoma cell lines. Furthermore, GAS5 showed no difference between healthy subjects and patients with chronic HBV in multiple GEO microarray data sets by GEO2R analysis. Taken together these results, GAS5 does not modulate the replication of HBV but it inhibits cell proliferation in HepAD38. This provides insights into the possible roles of GAS5 in HBV infection.

[Clinical Epidemiological Characteristics of Newly Reported HIV/AIDS in a Certain General Hospital from 2001 to 2017].

OBJECTIVE: To determine the clinical epidemiological characteristics of newly reported human immunodeficiency virus/acquired immunodeficiency syndrome （HIV/AIDS）in southwestern China from 2001 to 2017. METHODS: Clinical data of newly diagnosed HIV/AIDS from 2001 to 2017 in the West China Hospital of Sichuan University were reviewed and analyze. RESULTS: A total of 1 520 228 patients were screened for HIV, including 285 983 outpatient and emergency patients and 1 234 245 inpatients. About 4 037 (0.27%) patients were confirmed with HIV/AIDS. The confirmation rate increased from 2001 to 2013, followed by a slight decline from 2014 to 2017. The male to female sex ratio of confirmed HIV/AIDS was 3.49:1 from 2001 to 2017, ranging from 1.65:1 to 5.08:1. The majority of patients were identified as Han (88.23%), had low education (58.66%), and married (54.75%). Peasants/herdsman comprised 26.33% of the patients. The proportion of young (15-29 years old), and middle-aged (≥50 years old) patients and those who were unmarried and had high education (senior high school and above) increased over time. Heterosexual transmission remained stable at about 60% while homosexual transmission increased by about 15% ( χ 2=14.436, P＜0.005) since 2008. Transmissions through drug abuse( χ 2=71.633, P＜0.005) and blood( χ 2=16.672, P＜0.005) decreased. Of the 899 female newly reported HIV/ADIS patients, 77.20% were infected through heterosexual relationship. In comparison, of the 3 138 male patients, 61.41% were infected through heterosexual and 18.10% through homosexual relationships. Homosexual transmissions decreased with age, but heterosexual transmissions increased with age. Mother-to-child transmissions were concentrated in those between 0 and 15 years old (100%). CONCLUSION: Newly diagnosed HIV/AIDS cases increased over the years in the West China Hospital of Sichuan University, in particular in those of young and middle-aged, highly educated and unmarried. Heterosexual transmissions remain the main route.

High prevalence of syphilis, HBV, and HCV co-infection, and low rate of effective vaccination against hepatitis B in HIV-infected patients in West China hospital.

To investigate the epidemiological features and risk factors of HBV, HCV, and syphilis infection among HIV-infected patients in West China Hospital. A retrospective study was conducted with HIV-infected patients from 2014 to 2016 in West China hospital, SCU. Serum makers for HBV, HCV, and syphilis were detected. Among 894 HIV-infected patients, the prevalence of HIV/HBV, HIV/HCV, HIV/syphilis co-infections was 14.4%, 5.7%, and 18.9% respectively. HIV/HBV/HCV, HIV/HCV/syphilis, and HIV/HBV/syphilis triple co-infection was 7 (0.7%), 12(1.3%), 29(3.2%) respectively. The rate of effective vaccination against HBV was only 7.7% in HIV-infected patients. Age (OR = 0.243 95% CI: 0.114 -0.518), ethnicity (OR = 3.654 95% CI: 1.849-7.218) and education level (OR = 0.140 95% CI: 0.033-0.606) are risk factors affecting HIV/HCV co-infection. A high prevalence of HIV/syphilis, HIV/HBV, and HIV/ HCV co-infection can be observed in west China. The rate for HIV-infected patients who were effectively vaccinated against HBV was fewer than 10%.

BCP/PC mutation prevalence and their association with HBV replication in HIV/HBV co-infected patients.

The high prevalence (14.3%) of HIV/HBV co-infections reported in west China makes it necessary to screen concurrent HBV infection in HIV carriers. HBV B genotype was shown to be dominant in 54 cases of HIV/HBV co-infection, accounting for 81.48% of the total. The total drug resistance rate observed was 3.70%. A1762T, G1764A and G1896A mutations were common mutations identified in the BCP/PC region. However, the prevalence of the G1896A mutation was significantly high among the HBeAg negative HIV/HBV co-infected patients, and may be associated with high HBV replication. Mutations in the PC region are related to the loss in synthesis of HBeAg and may accelerate HBV replication in HIV positive patients.

M2BPGi as a potential diagnostic tool of cirrhosis in Chinese patients with Hepatitis B virus infection.

BACKGROUND: M2BPGi is a novel serum glycobiomarker of liver fibrosis. In this study, we aimed to evaluate the efficacy of M2BPGi for predicting liver fibrosis and disease progression in Chinese hepatitis B virus (HBV) infected patients. METHODS: We enrolled 228 HBV infected patients with different status of liver fibrosis diagnosed using FibroScan. We analyzed the diagnostic accuracy of M2BPGi, and compared it with AST-to-platelet ratio (APRI), FIB-4 index, AST to ALT ratio (AAR), and RDW to platelet ratio (RPR). We performed receiver operating characteristics curve (ROC) to evaluate the diagnostic performance of M2BPGi for significant fibrosis and cirrhosis. RESULTS: Median M2BPGi values in each fibrosis stage were: 0.88 cut-off index (COI) in F0-1, 1.165 in F2-3, and 1.92 in F4 (P<.01), respectively. For F≥2, the sensitivity, specificity, accuracy of M2BPGi were 72.28%, 73.23%, 66.67%, while 55.07%, 93.71%, 82.02% for F≥4. For predicting significant fibrosis (≥F2), M2BPGi showed comparable performance to FIB4 index (P<.01), APRI (P<.01) and RPR (P<.01) with area under the ROC curve (AUC) of 0.788. M2BPGi was superior to other surrogate markers for diagnosing cirrhosis (F4) with the highest AUC of 0.811 (P<.01). CONCLUSIONS: M2BPGi levels increased with the progression of liver fibrosis in HBV infected patients. M2BPGi can be served as a potential glycobiomarker to assess the stage of liver fibrosis, especially for the diagnosis of cirrhosis.

Pronounced decline of serum HBsAg in chronic hepatitis B patients with long-term effective nucleos(t)ide analogs therapy.

AIMS: This study aims to investigate the kinetics of serum HBsAg levels in chronic hepatitis B patients with long-term nucleos(t)ide analogs (NAs) therapy. METHODS: This was a retrospective clinical study. Serum HBsAg in serial samples of 94 patients, who received at least 8 years of NAs therapy, were measured using Elecsys® HBsAg II Quant Assay. RESULTS: In this cohort, serum HBsAg levels reduced from 3.80 log10 IU/mL at baseline to 2.72 log10 IU/mL at year 8 (p < .001), and the percentage of patients with HBsAg <1000 IU/mL increased from 14.9% at baseline to 55.3% at year 8 (p < .001). The reduction of serum HBsAg did not differ significantly between patients stratified by baseline virological parameters and type of antiviral agents. But as compared to patients without HBeAg seroconversion, HBsAg levels were significant lower in patients with HBeAg seroconversion (3.19 vs. 2.47 log10 IU/mL at year 8, p = .001). As compared to patients with slow (0-1 log10 IU/mL) or steady HBsAg(≤0 log10 IU/mL) decline at year 1, patients with a rapid HBsAg (≥1 log10 IU/mL) decline had a significantly lower HBsAg levels from year 2 to 8. However, Cox regression analysis showed that only absolute HBsAg levels at year 1 was an independent predictor of subsequent HBsAg <1000 IU/mL at year 8 of antiviral therapy(HR 0.242, p = .004). CONCLUSION: Pronounced HBsAg declines could be achieved in patients after long-term effective therapy with NAs, and on-treatment low serum HBsAg level at year 1 might be a predictor of serum HBsAg <1000 IU/mL at year 8.

Predictive Value of Hepatitis B Core-Related Antigen (HBcrAg) During the Natural History of Hepatitis B Virus Infection.

BACKGROUND: The natural history of HBV infection includes immune tolerance (IT), immune clearance (IC), HBeAg-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. As the current biomarkers for discriminating the four phases still have some weaknesses, additional serological indicators are needed. Hepatitis B core-related antigen (HBcrAg) encoded with the precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg), and a 22-KDa precore protein (p22cr) and has been demonstrated to have a close association with the natural history of hepatitis B infection. However, no specific cutoff values and diagnostic parameters have been identified to evaluate the diagnostic efficacy. This study aimed to clarify the distribution of HBcrAg levels and evaluate the diagnostic performance during the natural history of HBV infection in a Western Chinese population. METHODS: In this study, 294 samples were collected from treatment-naive HBV infection patients in different phases (IT = 64; IC = 72; ENQ = 100, and ENH = 58). We detected the HBcrAg values and analyzed the relationship between HBcrAg and HBV DNA. HBsAg and other clinical parameters were quantitatively detected. RESULTS: The HBcrAg levels of IT, IC, ENQ, and ENH were 9.30 log U/mL, 8.80 log U/mL, 3.00 log U/mL, and 5.10 log U/mL, respectively (p < 0.0001). Receiver operating characteristic curve analysis demonstrated that the areas under the curves (AUCs) for HBcrAg and quantitative HBsAg at cutoff values of 9.25 log U/mL and 4.355 log IU/mL for distinguishing the IT phase from the IC phase were 0.704 and 0.694, with a sensitivity of 53.13% and 79.69% and specificity of 76.39% and 59.72%, respectively. AUCs of HBcrAg and quantitative HBsAg at cutoff values of 4.15 log U/mL and 2.395 log IU/mL for discriminating between the ENQ and ENH phases were 0.931 and 0.653, with a sensitivity of 87.93% and 91.38% and specificity of 84.00% and 39.00%, respectively. CONCLUSIONS: HBcrAg levels varied significantly among the four natural phases of HBV infection and had higher predictive performance than quantitative HBsAg for distinguishing between ENQ-patients and ENH-patients and a similar performance as HBsAg for the discrimination between IT and IC phases, which indicated that HBcrAg could be a potential serological marker for HBV infection.

Performance Evaluation of a Novel Chemiluminescence Assay Detecting Treponema Pallidum Antibody as a Syphilis Screening Method.

BACKGROUND: Syphilis is a major concern to global public health with increasing incidence. So its screening test should have sufficient sensitivity and specificity. We evaluated the performance of the Lumipulse G TP-N assay detection for syphilis screening and compared it with the InTec ELISA test kit for TP, which is widely used. METHODS: Samples of several patient groups including 133 clinical and serologically characterized syphilitic sera, 175 samples containing potentially interfering agents, and 2290 unselected samples submitted for routine screening were detected by both the Lumipulse G TP-N assay and the InTec ELISA test kit for TP. Inconsistent samples were confirmed by RecomLine Treponema IgG, IgM immunoblot. RESULTS: Coefficient of variations of the Lumipulseo G TP-N assay at both levels were below 5% and of the InTec ELISA test kit for TP both over 5%. The sensitivity of the Lumipulse G TP-N assay and the InTec ELISA test kit for TP were 100% for all stages of syphilis. The two methods had consistent analytical specificity of 100% (95% CI: 97.21 - 100.00), while the clinical specificity was 100% (95% CI: 99.79 - 100.00) and 99.82% (95% CI: 99.51 - 99.94), respectively. Between them, Spearman's correlation coefficient was 0.455 and kappa value was 0.986. The overall sensitivity and specificity of the Lumipulse G TP-N assay was higher than the InTec ELISA test kit for TP (sensitivity: 100.0 versus 99.5, specificity: 100.0 versus 99.8). CONCLUSIONS: The automated Lumipulse G TP-N assay demonstrated excellent diagnostic sensitivity and specificity when evaluated as a screening test for syphilis. Thus, it can be an alternative to the treponemal screening test.

Clinical Evaluation of the Newly Developed HISCL-5000 Analyzer on Detection of Hepatitis B Virus Markers in West China Hospital.

BACKGROUND: Detection of serum hepatitis B virus (HBV) markers is important for rapid screening and diagnosis of HBV infection. In this study, the newly launched HISCL-5000 analyzer (Sysmex Corporation, Kobe, Japan) was appraised in parallel with the MODULAR E170 (Roche Diagnostics, Penzberg, Germany), with regard to the detection of serological HBV markers in China for comparing and evaluating their results and capability. METHODS: In this study, a total of 5,662 clinical serum samples were tested with the two automated systems. Among them, 1,266 samples were assessed for HBsAg, 1,000 for anti-HBs, 1,301 for HBeAg, 1,007 for anti-HBe, and 1,088 for anti-HBc. Reproducibility performance of HISCL-5000 was assayed four times per day for five days consecutively. For qualitative results between the two analyzers, the concordance rates and kappa coefficients were calculated. Spearman's rank correlation analysis was performed for quantitative results. RESULTS: The HISCL-5000 detection mode showed excellent reproducibility with total CVs of less than 5.0%. Concordance between the two analyzers was 99.92% for HBsAg, 95.90% for anti-HBs, 100% for HBeAg, 99.30% for anti-HBe, and 98.62% for anti-HBc. Kappa values between the qualitative results of five HBV markers were 0.998, 0.906, 1.0, 0.983, and 0.969, respectively. For anti-HBs, linear regression analysis demonstrated a good correlation between HISCL-5000 and MODULAR E170 with an R2 value of 0.887. Spearman's correlation coefficients of 0.892, 0.644, -0.609, and -0.700 were observed for the other four markers, HBsAg, HBeAg, anti-H1Be, anti-HBc, respectively. CONCLUSIONS: The newly launched HISCL-5000 displayed high agreement with the more matured MODULAR E170 on screening and diagnosing HBV infection in a clinical laboratory of West China Hospital.