Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Hepatitis B Surface Antigen Serum Level Is Correlated with Fibrosis Severity in Treatment-Naïve, Chronic Hepatitis B Patients in Côte d’Ivoire (West Africa)?

HBsAg serum level (quantification) may be useful for managing hepatitis B virus (HBV) infection patients. However few studies especially in Africa have evaluated the association between HBsAg serum level and liver fibrosis severity. The objective of this study was to estimate the correlation between HBsAg serum level and liver fibrosis severity with treatment naive chronic hepatitis B patients in Cote d’Ivoire. Methodology: It is a prospective study covering from February 1st, 2014 to April 30st, 2015 at Centre Hospitalier et Universitaire de Yopougon and a private medical office in Abidjan, Cote d’Ivoire. Inclusion criteria for patients were: HBsAg positive, known HBeAg status, serum HBsAg levels, serum HBV DNA levels, complex serum markers and absence of HCV, HDV, or HIV co-infection, drinking more than 30 g/day for men and 20 g/day in women over 10 years, metabolic disease and/or hepatic overload. Pearson’s Chi-square test (r2), Anova, Spearman, T-Student, Pearson’s (r) correlations and Mann Withney’s Test were carried out as appropriate. A p value < 0.05 was taken as significant. Results: We recruited, 105 patients (77 men) of whom the medium age was 39.01 ± 9.72 years. Predominant hepatitis B viral genotype was E (93%). Less than 10% patients had an inactive HBV in HBeAg-negative. Patients had an average high HBsAg serum level (mean 12111.2 ± 10617.4 IU/ml) as well as the one viral load (mean 4.4 e7 ± 7.5 e7). Serum ALAT levels averaged at the upper limit of normal value. The average liver fibrosis score was 0.34 ± 0.22 and the degree of viral activity was 0.19 ± 0.20. Half of our patients had no fibrosis (35.24%) or had mild fibrosis (20.95%). No significant association was observed between HBsAg serum level and patient age (p = 0.3994), genre (p = 0.8075) or serum ALT levels (p = 0, 0787). In multivariate analysis, there’s a significant correlation (r = 0.239, p = 0.014) between HBV DNA levels and HBsAg serum level. There’s a significant correlation (r = 0.923, p < 0.0001) between HBsAg serum level and the dosage of alpha-fetoprotein. HBsAg serum level was not associated with the fibrosis stage (p = 0.281). HBsAg levels average with patients without fibrosis or carry a slight fibrosis (F0, F1) was higher than patients with moderate to severe fibrosis (F2, F3, F4): 13679.2 UI/ml ± 1956.48 versus 10610.52 UI/ml ± 8998.99 (p = 0.29). There’s a negative correlation between HBsAg level and the liver fibrosis score was negative (r = -0.069, p = 0.48). No significant association between HBsAg level and the liver fibrosis patients that were normal (p = 0.7965) or elevated (p = 0.5845). HBV DNA level was significantly associated with fibrosis score (r = 0.30, p = 0.0018). Conclusion: This study shows that there’s a negative correlation between HBsAg serum level and liver fibrosis severity treatment naive with African chronic hepatitis B viral HBeAg-negative patients.

Predictors of loss of hepatitis B surface antigen in HIV-infected patients

AIM:To study factors associated with loss of hepatitis B surface antigen (HBsAg) in patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV).METHODS:We retrospectively reviewed the medical records of 5681 patients followed up at two New York City HIV clinics from January 1999 to May 2007.Clinical and laboratory parameters including baseline and follow-up HIV viral loads,CD4 cell counts,alanine transaminase levels,demographics,presence of hepatitis C infection,and treatment with highly active antiretroviral therapy dually active against both HIV and HBV infection,were analyzed to determine factors associated with loss of HBsAg.RESULTS:Three hundred and fifty five patients (355/5681,6.84%) were co-infected with HIV and HBV and were evaluated.Of these,226 patients with more than 12 mo follow-up were included in further analysis to determine factors associated with loss of HBsAg in the long-term follow-up.In the univariate analysis,baseline CD4 cell count was associated with loss of HBsAg (P=0.052).Cox regression analysis revealed that loss of HBsAg was associated with baseline CD4 cell count > 500 cells/mm3 (P=0.016,odds ratio:76.174,95% confidence interval:2.233-2598.481).CONCLUSION:Our study showed an interesting association of loss of HBsAg in HIV-HBV co-infected patients with higher CD4 cell count,suggesting that T-cell cytolytic activity against HBV may still be effective in clearing HBV infection.

HBV C基因型有关的HBsAg阴性HBV DNA阳性患者S区突变对HBsAg的影响

目的通过构建HBV C基因型突变质粒研究HBsAg阴性HBV DNA阳性患者HBV S区突变对HBsAg水平的影响。方法收集2022年8月至2023年4月首都医科大学附属北京佑安医院107例HBsAg-/HBV DNA+患者血液样本,对成功提取扩增的HBV DNA S区进行测序,通过构建HBV C基因型突变质粒对HBV S区突变位点进行细胞功能验证,探讨OBI可能发生的分子机制。结果对成功提取扩增的68例患者进行测序,发现HBV S区存在大量突变,包括免疫逃逸突变(如sG145R、sK122R、sS114T、sT131P等)和跨膜结构域(transmembrane domain,TMD)突变(如sT5A、sG10D、sF20S等)。通过构建HBV C基因型突变质粒,进行细胞转染和细胞免疫荧光实验发现sG145R突变会明显降低HBsAg的表达,但是sK122R、sI26N、sQ29N、sR169H、sS114T、sT131P这6个突变位点并未影响细胞内外HBsAg的表达。结论通过测序发现HBsAg-/HBV DNA+患者HBV S区存在大量突变位点,通过构建sG145R、sK122R、sI26N、sQ29N、sS114T和ST131P等突变质粒发现sG145R突变会明显降低细胞内外HBsAg的表达,但是sK122R、sI26N、sQ29N、sR169H、sS114T、sT131P并未明显降低细胞内外HBsAg的表达。

Detection of anti-preS1 antibodies for recovery of hepatitis B patients by immunoassay

AIM: To establish a convenient immunoassay method based on recombinant antigen preS1(21-119aa) to detect anti-preS1 antibodies and evaluate the clinical significance of antibodies in hepatitis B. METHODS: The expression plasmid pET-28a-preS1 was constructed, and a large quantity of preS1(21-119aa) fragment of the large HBsAg protein was obtained. The preS1 fragment purified by Ni(2+)-IDA affinity chromatography was used as coated antigen to establish the indirect ELISA based on streptavidin-biotin system for detection of the anti-preS1 antibodies in sera from HBV-infected patients. For follow-up study, serial sera were collected during the clinical course of 21 HBV-infected patients and anti-preS1 antibodies, preS1 antigen, HBV-DNA and other serological HBV markers were analyzed. RESULTS: preS1(21-119aa) fragment was highly expressed from the plasmid pET-28a-preS1 in a soluble form in E.Coli (30mg.L(-1)), and easily purified to high purity over 90% by one step of Ni(2+)-IDA-sepharose 6B affinity chromatography. The purity and antigenicity of the purified preS1(21-119aa) protein was determined by 150g.L(-1) SDS-PAGE, Western blot and a direct ELISA. Recombinant preS1(21-119aa) protein was successfully applied in the immunoassay which could sensitively detect the anti-preS1 antibodies in serum specimens of acute or chronic hepatitis B patients. Results showed that more than half of 19 acute hepatitis B patients produced anti-preS1 antibodies during recovery of the disease, however, the response was only found in a few of chronic patients. In the clinical follow-up study of 11 patients with anti-preS1 positive serological profile, HBsAg and HBV-DNA clearance occurred in 6 of 10 acute hepatitis B patients in 5-6 months, and seroconversion of HBeAg and disappearance of HBV-DNA occurred in 1 chronic patients treated with lavumidine, a antiviral agent. CONCLUSION: The high-purity preS1(21-119aa) coated antigen was successfully prepared by gene expression and affinity chromatography. Using this antigen, a conveniently detective system of anti-preS1 antibodies in sera was established. Preliminarily clinical trial the occurrence of anti-preS1 antibodies in acute hepatitis B patients suggests the clearance of HBV from serum in a short-term time, and anti-preS1 positive in chronic patients means health improvement or recovery from the disease.

Serum concentration of sFas and sFasL in healthy HBsAg carriers,chronic viral hepatitis B and C patients

AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS:Eighty-six persons were included into study:34 healthy HBsAg carders,33 patients with chronic HBV infecl^on and 19 patients with chronic HCV infection.Serum levels of sFas/sFasL were measured by ELISA assay.HBV-DNA and HCV-RNA were measured by RT-PCR assay.Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS:Twenty-four (71%) healthy HBsAg carders showed HBV-DNA over 10~5/mL,which was comparable to the patients with chronic hepatitis B.independently from HBV-DNA levels, the concentration of sFas among healthy HBsAg carders was comparable to healthy persons.Among patients with chronic hepatitis B and C,the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons.In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment.Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment,sFasL was not detected in control group.Furbhermore sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION:There are no correlations between apoptosis and HBV-DNA levels.However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection.Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.

Effects of hepatitis B virus infection on human sperm chromosomes

AIM: To evaluate the level of sperm chromosome aberrations in male patients with hepatitis B, and to directly detect whether there are HBV DNA integrations in sperm chromosomes of hepatitis B patients.METHODS: Sperm chromosomes of 14 tested subjects (5healthy controls, 9 patients with HBV infection, including 1with acute hepatitis B, 2 with chronic active hepatitis B, 4with chronic persistent hepatitis B, 2 chronic HBsAg carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free golden hamster ova and human spermatozoa, and the frequencies of aberration spermatozoa were compared between subjects of HBV infection and controls. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes.RESULTS: The total frequency of sperm chromosome aberrations in HBV infection group (14.8%, 33/223) was significantly higher than that in the control group (4.3%,5/116). Moreover, the sperm chromosomes in HBV infection patients commonly presented stickiness, clumping, failure to staining, etc, which would affect the analysis of sperm chromosomes. Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis. In 9 (9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots, others presented 2 to 4signals. There was significant difference of fluorescence intensity among the signal spots. The distribution of signal sites among chromosomes was random.CONCLUSION: HBV infection can bring about mutagenic effects on sperm chromosomes. Integrations of viral DNA into sperm chromosomes which are multisites and nonspecific, can further increase the instability of sperm chromosomes. This study suggested that HBV infection can create extensively hereditary effects by alteration genetic constituent and/or induction chromosome aberrations, as well as the possibility of vertical transmission of HBV via the germ line to the next generation.

Association between metabolic factors and chronic hepatitis B virus infection

There are limited data regarding the relationship between chronic hepatitis B virus(HBV)infection and metabolic factors.This article aims to highlight the link of metabolic factors with hepatitis B surface antigen(HBsAg)serostatus,HBV load,and HBV-related hepatocellular carcinoma(HCC).Although HBsAg-positive serostatus was positively correlated with a high risk of metabolic syndrome in students,chronic HBV-infected individuals have high serum adiponectin levels.The androgen pathway in HBV carriers with a low body mass index is more triggered which leads to enhanced HBV replication.High HBV load was inversely associated with obesity in hepatitis B e antigen(HBeAg)-seropositive HBV carriers;while in HBeAg-seronegative HBV carriers,high HBV load was inversely related to hypertriglyceridemia rather than obesity.For overweight and obese HBV-infected patients,high HBV load was positively associated with serum adiponectin levels.Several large cohort studies have revealed a positive link of diabetes with incidence of HBV-related HCC.However,the association between incidence of HCC and metabolic factors other than diabetes is still inconclusive.More long-term prospective studies should elucidate the association of chronic HBV infection and its outcomes with metabolic factors in clinical practice.

Inhibition of hepatitis B virus by oxymatrine in vivo

AIM To investigate the anti-HBV effect ofoxymatrine (oxy) in vivo.METHODS HBV transgenic mice were producedby micro-injection of a 4.2kb fragmentcontaining the complete HBV genomes.Expression level of HBsAg and HBcAg in thetransgenic mice liver was determined byimmunohistochemical assay.RESULTS Four groups (6 mice in each group)were injected intraperitoneally with oxy at thedosage of 100,200, and 300 mg/kg or with salineonce a day for 30 days. Both HBsAg and HBcAgwere positive in livers of all the six mice in thecontrol group (injected with saline), and werepositive in livers of two mice in 100 mg/kg groupand 300mg/kg group. In 200mg/kg group,HBsAg and HBcAg were negative in livers of allthe six mice. Based on the results, 200 mg/kg isthe ideal dosage to explore the effect of oxy atdifferent time points. According to the oxytreatment time, mice were divided into fourgroups: 10 d, 20 d, 30 d and 60 d (4 mice in eachgroup). Each mouse underwent liver biopsy twoweeks before the treatment of oxy. Down-regulation of HBsAg and HBcAg appeared aftertreatment of oxymatrine for 10 d and 20 d, Dane-like particles disappeared after the treatment ofoxy for 20d under electron microscopy,however, the expression level of HBsAg andHBcAg returned to normal 60 d later after oxytreatment.CONCLUSION oxymatrine can reduce thecontents of HBsAg and HBcAg in transgenic miceliver, longer treatment time and larger dosagedo not yield better effects.

A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong,China

AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.

Establishment of transgenic mouse harboring hepatitis B virus (adr subtype) genomes

INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).

A comparative study on serologic profiles of virus hepatitis B

INTRODUCTIONHepatitis B viral infection, one of the most-prevalent liver disorders in China and Korea, is aserious infectious disease as it has the potential ofprogressing into liver cirrhosis and primary hepaticcarcinoma. China and Korea both belong to high-risk endemic regions of viral hepatitis[1]. TheHBsAg positive rates in China ranged from 6.9% -17.9% by age, race and test methods[2-5].

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

Molecular interactions between hepatitis B virus and delta virus

As a deficient virus due to the lack of envelope proteins, hepatitis D virus(HDV) causes chronic or fulminant "delta hepatitis" only in people with simultaneous hepatitis B virus(HBV) infection. HBV encodes three types of surface proteins known as small(S), medium(M) and large(L) envelope proteins. All three types of HBV surface antigens(HBs Ags) are present on HDV virions. The envelopment process of HDV occurs through interactions between the HDV ribonucleoprotein(RNP) complex and HBV HBsA gs. While HBsA g is the only protein required by HDV, the exact interaction sites between the S protein and pre-mature HDV are not well defined yet. In fact, these sites are distributed along the S protein with some hot spots for the envelopment process. Moreover, in most clinically studied samples, HDV infection is associated with a dramatically reduced HBV viral load, temporarily or permanently, while HBsA g resources are available for HDV packaging. Thus, beyond interacting with HBV envelope proteins, controlling mechanisms exist by which HDV inhibits HBV-DNA replication while allowing a selective transcription of HBV proteins. Here we discuss the molecular interaction sites between HBs Ag and the HDV-RNP complex and address the proposed indirect mechanisms, which are employed by HBV and HDV to facilitate or inhibit each other's viral replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies for delta hepatitis.

建立HBV DNA阳性诊断模型及应用分层分析探寻化学发光法检测HBsAg的最佳临界值

目的建立乙型肝炎病毒(HBV)DNA阳性诊断模型及应用分层分析探寻化学发光法检测乙型肝炎(简称乙肝)表面抗原(HBsAg)的最佳临界值。方法收集2018年4月至2022年7月长江大学附属荆州医院行乙肝血清标志物定量检测且行HBV DNA检测的患者6021例,将研究群体的70%(4229例)纳入训练集建立HBV DNA阳性(≥2 log_(10)IU/ml)诊断模型,30%(1792例)纳入验证集行内部验证。依据HBsAg水平将研究人群(6021例)分为10组,探讨各组HBV DNA阳性率的差异。结果本研究选取训练集建立预测模型,其中DNA阴性2787例、DNA阳性1442例。HBsAg 0、0.01、0.02、0.03~0.09、0.1~0.99、1~9.9、10~99、100~999、1000~2500 IU/ml组分别为1039例、74例、26例、124例、276例、421例、896例、1812例、680例、673例。DNA阳性组年龄、乙肝表面抗体(HBsAb)水平低于DNA阴性组[44(33,52)岁比46(35,54)岁、0.30(0.10,0.60)mIU/ml比0.40(0.20,2.40)mIU/ml](P<0.01),HBV DNA、HBsAg、乙肝e抗原(HBeAg)、乙肝e抗体及乙肝核心抗体(HBcAb)水平高于DNA阴性组[3.9(3.0,5.2)log_(10)IU/ml比0.0(0.0,0.0)log_(10)IU/ml、547.0(102.0,2219.4)IU/ml比25.3(0.5,72.0)IU/ml、0.0(0.0,0.9)COI比0.0(0.0,0.0)COI、100(60,100)Inh%比95(57,100)Inh%、609(447,761)COI比256(60,525)COI](P<0.01)。多因素Logistic回归分析显示,HBsAg、HBsAb、HBeAg及HBcAb水平是HBV DNA的影响因素(OR=1.001,95%CI 1.000~1.001;OR=0.998,95%CI 0.996~0.999;OR=1.001,95%CI 1.001~1.001;OR=1.004,95%CI 1.004~1.004)(均P<0.01)。应用此4因子构建列线图,结果显示:HBsAg、HBeAg及HBcAb水平升高是HBV DNA阳性的促进因素,HBsAb水平升高是HBV DNA阳性的抑制因素。内部验证显示,该模型稳定性及准确性均良好。HBsAg分层分析显示:HBsAg 0.01、0.02、0.03~0.09、0.1~0.99、1~9.9、10~99、100~999、1000~2500、>2500 IU/ml组HBV DNA阳性率均高于0 IU/ml组(P<0.05或P<0.01),HBsAg 0.03~0.09 IU/ml组与HBsAg 0.01、0.02 IU/ml组HBV DNA阳性率比较差异无统计学意义(P>0.05),HBsAg 0.1~0.99 IU/ml组与HBsAg 0.01、0.02 IU/ml组HBV DNA阳性率比较差异无统计学意义(P>0.05)。结论CLEIA方法检测HBsAg 0.01~0.02 IU/ml的患者体内也可能存在病毒复制,HBsAg 0.01~1 IU/ml的患者体内病毒复制的能力大致相同,均应被考虑为HBV感染患者。CLEIA方法检测HBsAg的临界值应由0.03 IU/ml下调至0.01 IU/ml,以减少漏诊。

血清HBsAg和HBeAg定量检测评估恩替卡韦治疗乙型肝炎肝硬化合并原发性肝癌患者病毒应答的临床价值

目的探讨定量检测乙肝病毒表面抗原(HBsAg)和乙肝病毒E抗原(HBeAg)血清水平评估恩替卡韦治疗乙型肝炎肝硬化合并原发性肝癌患者病毒应答(HBV-DNA)的临床价值。方法选取我院2020年4月至2021年7月收治的80例乙型肝炎中度肝硬化合并原发性肝癌Ⅱa期患者,根据治疗的第8周时是否发生病毒学应答分为应答组47例和未应答组33例。比较患者治疗前后血清HBsAg、HBeAg水平与HBV-DNA水平的相关性,受试者工作特征(ROC)曲线确定血清HBsAg、HBeAg水平对病毒应答的预测价值,Kaplan-Meier法生存分析1年生存率。结果患者治疗前血清HBsAg、HBeAg水平与HBV-DNA水平呈正相关,患者治疗第8、12、24、36、48周时血清HBsAg和HBeAg水平变化差异均有统计学意义(P<0.01)。治疗第48周时,血清HBsAg水平预测病毒应答ROC曲线下面积最大0.818(95%CI:0.709~0.965),最佳截点为(40.63±10.28)ng/mL,灵敏度为91.34%,特异度为71.93%;治疗第8周时,血清HBeAg水平预测病毒应答的ROC曲线下面积最大0.801(95%CI:0.673~0.979),最佳截点为(53.38±9.86)NCU/mL,灵敏度为88.52%,特异度为83.42%。生存分析结果显示,应答组1年生存率为87.31%高于未应答组62.18%,差异有统计学意义(P<0.05)。结论恩替卡韦治疗的乙型肝炎肝硬化合并原发性肝癌患者血清HBsAg和HBeAg水平与病毒应答存在相关性,定量检测血清HBsAg和HBeAg水平评估患者病毒应答具有较高临床价值。

HBsAg/HBV DNA值与乙型肝炎患者TGF-β1、Tim-3水平的关系

【目的】探讨乙型肝炎患者乙型肝炎表面抗原(HBsAg)/乙型肝炎病毒(HBV)DNA值与转化生长因子-β1(TGF-β1)、T淋巴细胞免疫球蛋白黏蛋白分子3(Tim-3)水平的关系。【方法】两院收治的70例乙型肝炎患者,依据病情严重程度将患者分为轻度HBV组(22例)、中度HBV组(30例)、重度HBV组(18例),另选同期体检的健康志愿者30例为对照组。收集所有研究对象的临床血生化资料,比较各组肝功能指标及HBsAg/HBV DNA、TGF-β1、Tim-3水平,采用Pearson相关分析HBsAg/HBV DNA值与乙型肝炎患者TGF-β1、Tim-3水平的关系。【结果】不同病情严重程度的HBV患者及对照组间血清谷丙转氨酸(ALT)、谷草转氨酸(AST)、总胆红素(TBIL)、血小板计数(PLT)水平比较,均为对照组<轻度HBV组<中度HBV组<重度HBV组,且各组比较差异均有统计学意义(均P<0.05)。各组HBsAg/HBV DNA值比较,轻度HBV组>中度HBV组>重度HBV组(均P<0.05);各组TGF-β1、Tim-3水平比较,对照组<轻度HBV组<中度HBV组<重度HBV组(均P<0.05)。HBsAg/HBV DNA比值与乙型肝炎患者TGF-β1、Tim-3水平呈显著负相关(P<0.05)。【结论】乙型肝炎患者HBsAg/HBV DNA值与TGF-β1、Tim-3水平呈显著负相关。

不同环境温度对胶体金免疫层析法测定血清低浓度HBsAg的效果评价

目的 探讨与评价环境温度对胶体金免疫层析法血清测定低浓度乙型肝炎表面抗原(HBs Ag)的影响。方法选择2019年6月到2022年3月在广东省韶关市中医院诊治的150例乙型肝炎患者作为研究对象,将血液样本采用胶体金免疫层析法试剂盒检测HBs Ag,分别置于室温25℃的室内(对照组)与37℃水浴箱(观察组)中,比较两种温度下胶体金免疫层析法检测的阳性率。同时以电化学发光免疫分析法作为参考的标准,比较两组的检测符合率以及灵敏度。结果 观察组的胶体金免疫层析法读取时间与报告时间都明显少于对照组(P <0.05)。在150例患者中,电化学发光免疫法检测浓度分别为0~1 COI 42例,2~15 COI 30例,16~50 COI 39例,>50 COI 39例。对照组判断为阳性48例,观察组判断为阳性75例,对照组的阳性符合率为44.44%,观察组的阳性符合率为69.44%,观察组的符合率明显高于对照组(P <0.05)。结论 胶体金免疫层析法检测HBs Ag置于37℃的实验环境条件下可以提高诊断的符合率,还可缩短读取时间与报告时间,具有很好的临床应用价值。

血清HBsAg和HBV DNA定量水平预测慢性乙型肝炎患者肝组织炎症活动度和纤维化程度的评价

目的评价血清HBsAg水平和HBVDNA载量预测CHB患者肝组织炎症活动度和纤维化程度的效能。方法740例CHB患者被随机分成训练集和验证集，训练集HBeAg阳性和阴性患者分别为281例和169例，验证集HBeAg阳性和阴性患者分别为170例和120例。肝活检取得肝组织，将肝组织病理学分级和分期≥G2和≥S2、≥G3和≥S3，≥G4和≥S4分别定义为显著炎症和纤维化、严重炎症和纤维化、进展期炎症和纤维化。采用Abbott Architect I2000检测血清HBsAg，采用实时定量PCR法检测血清HBVDNA。结果在HBeAg阳性患者，训练集血清HBsAg水平预测严重纤维化和进展期纤维化的效能达到了中度，其ROC曲线下面积分别为0．707和0．726；基于Youden指数确定的血清HBsAg预测严重纤维化和进展期纤维化的最佳截断点为≤6．683×10^3IU／ml和≤6．427×10^3IU／ml，在训练集其对应的灵敏度和特异度分别为0．682和0．754及0．673和0．634，在验证集则分别为0．667和0．806及0．644和0．619；在HBeAg阴性患者，训练集血清HBVDNA载量有预测显著炎症和显著纤维化的效能，其ROC曲线下面积分别为0．629和0．671。基于Youden指数确定的血清HBVDNA预测显著炎症和显著纤维化的最佳截断点为94．315×10^4IU／ml和≥2．748×10^3IU／ml，在训练集其对应的灵敏度和特异度分别为0．444和0．606及0．795和0．717，在验证集则分别为0．446和0．613及0．797和0．622。结论血清HBsAg水平对HBeAg阳性患者的严重纤维化和进展期纤维化有显著的预测价值，而血清HBVDNA载量对HBeAg阴性患者的显著炎症和显著纤维化有一定的预测意义。

HBsAg水平在慢性HBV感染者疾病进展中的动态监测价值

目的探讨HBsAg水平在慢性HBV感染者疾病进展监测中的临床价值。方法收集2011年5月-2015年12月在安徽医科大学第二附属医院门诊及住院时未进行抗病毒治疗的1107例不同临床阶段的慢性HBV感染者的临床资料,并根据疾病状态分为HBeAg阳性慢性乙型肝炎组(HBeAg阳性CHB组,n=356)、HBeAg阴性慢性乙型肝炎组(HBeAg阴性CHB组,n=264)、乙型肝炎肝硬化代偿期组(LC-C组,n=116)、乙型肝炎肝硬化失代偿期组(LC-D组,n=201)、原发性肝癌组(PLC组,n=170),比较不同临床阶段患者之间HBsAg表达水平的差异及HBsAg水平与临床特征的相关性。计量资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验;两组间比较采用t检验。计数资料组间比较采用χ2检验。相关性分析采用Pearson检验。结果HBeAg阳性CHB组、HBeAg阴性CHB组、LC-C组、LC-D组、PLC组之间患者血清HBsAg、HBV DNA水平比较,差异均有统计学意义(F值分别为100.45、86.26,P值均<0.001)。502例HBeAg阳性患者的HBsAg、HBV DNA水平均高于605例HBeAg阴性患者(t值分别为16.67、16.22,P值均<0.001)。HBeAg阳性值均CHB、LC-C、LC-D和PLC 4组间HBsAg和HBV DNA水平差异均有统计学意义(F值分别为42.92、27.38,P值均<0.001);HBeAg阴性的CHB、LC-C、LC-D和PLC 4组间的HBsAg和HBV DNA水平差异亦均有统计学意义(F值分别为6.04、4.10,P值均<0.05)。不同HBsAg水平(<1000 IU/ml、1000~20 000 IU/ml、>20 000 IU/ml)患者间HBV DNA水平差异有统计学意义(F=189.51,P<0.001)。HBeAg阳性CHB组、HBeAg阴性CHB组、LC-C组、LC-D组患者血清HBsAg水平与HBV DNA水平均呈正相关(r值分别为0.554、0.501、0.320、0.432,P值均<0.001)。结论 HBsAg定量水平随疾病进展而逐步降低,且HBsAg与HBV DNA水平密切相关,动态监测HBsAg变化有助于发现HBV感染后疾病进展情况。