Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report

BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

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.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

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。

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Clinical utility of hepatitis B surface antigen kinetics in treatment-na?ve chronic hepatitis B patients during longterm entecavir therapy

AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen(HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, oneyear and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTS A total of 211 patients were enrolled. The median treatment time was 5.24(2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen(HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients(cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients(cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSION Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature

The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus(HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen(HBs Ag) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBs Ag-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBs Ag positive grafts have preferentially been allocated to HBs Ag positive recipients. The large majority of these patients continue to be HBs Ag positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBs Ag negative recipients, although they are mostly promising. HBs Agpositive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.

Hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited

Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection.

The Expression of Sperm Membrane Peptide-Hepatitis B SurfaceAntigen Fusion Protein with Recombinant Vaccinia Virus

A synthetic oligonucleotide, HSD-2a, encoding a peptide segment of the extracel-lular domain of a human sperm membrane protein, YWK-II, was fused with hepatitisB surface antigen gene (HBs gene ). The fused gene was then cloned to pUC18plasmid. The fused gene was prepared from the recombinant pUC18 plasmid byBamH I and Eco R I digestion, and then cloned into the transfer vector pGJP- 5 underthe control of P;., promoter, designated as pGJP-HSD/HBs. CV-1 cells were co-transfected with vaccinia virus (Tian Tan strain) and pGJP-HSD/IIBs and homolo-gous re combination occurred between the vaccinia virus TK gene of the plasmid flank-ing the foreign gene and the same sequences within the virus genome. TK phen0tyPerecombinant virus, vv-HSD/HBs, were selected from trandected HuTK' cells byplaque purthcation technique. The eopressi0n of HSD-b in spent medium and cellu-lar protein of HuTK cells infected with vv-HSD/HBs was determined by ELISAand Western-blot analysis using anti-rwK-II antiserum. The present study indicatesthat the vv-HSD/HBs seems promising as an antdertility vaccine.

恩替卡韦序贯联合聚乙二醇干扰素α-2b治疗低水平HBsAg阳性CHB患者疗效观察

目的:探讨恩替卡韦序贯联合聚乙二醇干扰素α-2b(Peg-IFN-α)治疗低水平乙型肝炎表面抗原(HBsAg)阳性慢性乙型肝炎(CHB)患者疗效。方法:选取2019年1月至2021年6月南通大学附属南通第三医院收治的120例HBsAg≤1500 IU/ml的CHB患者,通过随机数表发法分为恩替卡韦组(恩替卡韦治疗)、序贯组(序贯联合Peg-IFN-α治疗)和Peg-IFN-α组(Peg-IFN-α治疗)各40例,均持续治疗48周。比较3组患者治疗前后血清HBsAg水平、HBV DNA载量、HBsAg阴转率;Pearson相关性分析3组患者治疗前后血清HBsAg水平与HBV DNA载量的关系;比较3组患者治疗前后血清丙氨酸转移酶(ALT)、谷草转氨酶(AST)水平及治疗期间不良事件发生率。结果:序贯组、恩替卡韦组和Peg-IFN-α组各脱落2例、1例和4例,分别有38例、39例和36例患者完成48周疗程,3组间失访率差异无统计学意义(P>0.05);治疗12周和48周,序贯组血清HBsAg水平、HBV DNA载量低于恩替卡韦组和Peg-IFN-α组,血清HBsAg阴转率均高于恩替卡韦组和Peg-IFN-α组(P<0.05);Pearson相关性分析,治疗48周,序贯组、恩替卡韦组和Peg-IFN-α组的血清HBsAg水平与HBV DNA载量均呈显著正相关(P<0.05);治疗12周和48周,序贯组ALT、AST水平低于恩替卡韦组和Peg-IFN-α组(P<0.05);序贯组总不良事件发生率(47.37%)与恩替卡韦组(28.21%)和Peg-IFN-α组(27.77%)均无显著差异(P>0.05)。结论:恩替卡韦序贯Peg-IFN-α治疗可提高低水平HBsAg阳性CHB患者血清HBsAg阴转率,降低血清HBsAg和肝功能指标水平。

血清ALT串联HBsAg和串联HBV DNA识别HBeAg阳性慢性HBV感染非活动性肝炎的性能评价

乙型肝炎病毒(hepatitis B virus,HBV)e抗原(hepatitis B e antigen,HBeAg)阳性的慢性HBV感染依次经历非活动性肝炎(non-aggressive hepatitis,NAH)和活动性肝炎(aggressive hepatitis,AH)2个分期,但仍缺乏界定HBeAg阳性NAH与AH的可靠标准。本文根据179例患者的长期随访队列,以自发性HBeAg血清转换作为终点事件,采用Kaplan-Meier生存分析,指定了丙氨酸转氨酶(alanine transaminase,ALT)、HBV表面抗原(hepatitis B surface antigen,HBsAg)和HBV DNA识别HBeAg阳性NAH的功能截断值;在此基础上,评价了ALT串联HBsAg和串联HBV DNA识别HBeAg阳性NAH的性能。结果显示,ALT≤60 IU/L、HBsAg>4.602 log10IU/mL和HBV DNA>7.477 log10IU/mL为识别HBeAg阳性NAH的功能截断值。基于功能截断值,ALT串联HBsAg的患者中,病理学分级≤G1和“分级≤G1且分期≤S2”的构成比均为100%,病理学分期≤S1和“分级≤G2且分期≤S1”的构成比均为68.2%;ALT串联HBV DNA的患者中,病理学分级≤G1和“分级≤G1且分期≤S2”的构成比均为86.2%,病理学分期≤S1和“分级≤G2且分期≤S1”的构成比均为69.0%;ALT串联HBsAg识别病理学分级≤G1和“分级≤G1且分期≤S2”的阳性似然比均为+∞,识别病理学分期≤S1和“分级≤G2且分期≤S1”的阳性似然比均为2.034;ALT串联HBV DNA识别病理学分级≤G1和“分级≤G1且分期≤S2”的阳性似然比分别为3.000和3.068,识别病理学分期≤S1和“分级≤G2且分期≤S1”的阳性似然比均为2.106。以上结果提示,ALT串联HBsAg和串联HBV DNA均可有效识别HBeAg阳性NAH;且ALT串联HBsAg识别HBeAg阳性NAH的性能优于ALT串联HBV DNA。

非活动性HBsAg妇女妊娠期及产后HBV再激活的临床特征及危险因素分析

目的分析非活动性乙型肝炎病毒表面抗原(hepatitis B virus surface antigen,HBsAg)妇女妊娠期及产后乙型肝炎病毒(hepatitis B virus,HBV)再激活的临床特征及危险因素分析。方法回顾性选取非活动性HBV携带孕妇116例为研究对象。分析妊娠期HBV再激活组与妊娠期HBV未再激活组的基线资料,构建基线资料的临床预测模型并评估模型科学性;分析妊娠期HBV再激活、产后HBV再激活及妊娠期+产后HBV再激活孕妇在HBV激活时的肝功能、免疫功能、肝纤维化指标及炎症因子水平;评估妊娠期HBV再激活影响因素对全因性产后HBV再激活的影响。结果妊娠期HBV再激活组基线HBV脱氧核糖核酸(deoxyribonucleic acid,DNA)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)水平、初产妇比例明显高于HBV未再激活组,年龄、家庭月收入水平明显低于HBV未再激活组(χ^(2)/t=7.004,5.934,4.805,3.853,10.561,7.289,P<0.05)。基线HBV DNA水平、年龄、家庭月收入对妊娠期HBV再激活具有一定的预测价值(c指数=0.653,AUC 5个月内=0.679,AUC 10个月内=0.742,P<0.05)。仅发生妊娠期HBV再激活组HBV DNA水平、血清透明质酸、层黏连蛋白、三型前胶原N端肽、四型胶原蛋白、C反应蛋白、白细胞介素6、肿瘤坏死因子α低于仅发生产后HBV再激活组、妊娠期+产后HBV再激活组,CD4^(+)、CD4^(+)/CD8^(+)水平明显高于仅发生产后HBV再激活组、妊娠期+产后HBV再激活组(F=5.123、4.835、5.035、17.329、14.924、16.392、14.320、7.852、14.824、6.392,P<0.05)。年龄较低孕妇容易发生全因性产后HBV再激活(P<0.05)。结论年龄低、基线HBV DNA水平高及家庭月收入低的患者容易发生妊娠期HBV再激活,产后HBV再激活所引起的免疫损伤可能较妊娠期更为严重,年龄低者容易发生全因性产后HBV再激活。

HBsAg阳性孕妇及新生儿血清IL-6、IL.17、IL-23水平与HBV宫内感染关系

目的:探讨乙肝表面抗原(HBsAg)阳性孕妇及新生儿血清白细胞介素(IL)-6、IL-17、IL-23水平与乙肝病毒(HBV)宫内感染关系。方法:回顾性收集2021年1月-2023年12月本院就诊的HBsAg阳性孕妇140例的临床资料为HBsAg阳性组,按照新生儿脐带血检测结果分为宫内感染组(n=28)与未感染组(n=112),同期HBsAg阴性孕妇140例为HBsAg阴性组。比较孕妇孕28周时外周血及新生儿脐血血清IL-6、IL-17、IL-23水平。受试者工作特征(ROC)曲线分析HBsAg阳性孕妇血清IL-6、IL-17、IL-23水平判断HBV宫内感染临床价值。结果:宫内感染组孕妇血清IL-6(104.33±24.92 ng/L)、IL-17(282.65±76.71 ng/L)、IL-23(269.52±64.28 ng/L)水平均高于未感染组(70.34±18.61、123.41±43.02、113.75±41.68)ng/L与HBsAg阴性组(68.13±17.18、119.53±37.13、110.32±44.43)ng/L(均P<0.05),未感染组与HBsAg阴性组无差异(P>0.05),各组新生儿脐带血清IL-6、IL-17、IL-23水平无差异(P>0.05)。ROC曲线分析,HBsAg阳性孕妇血清IL-6、IL-17、IL-23评估HBV宫内感染的曲线下面积分别为0.791、0.725、0.745,敏感度及特异度在61.6%~78.6%,有一定临床参考价值。结论:宫内感染孕妇孕28周时血清IL-6、IL-17、IL-23水平升高,3项指标对判断HBsAg阳性孕妇发生HBV宫内感染风险有一定临床指导价值。

阿拉尔市某医院HBsAg阳性孕妇血清标志物模式分布与HBV-DNA载量分析

目的分析阿拉尔市某医院的乙型肝炎病毒表面抗原(HBsAg)阳性孕妇乙型肝炎病毒(HBV)感染血清标志物模式与HBV-DNA载量之间的关系,为监控孕期HBV感染和预防阻断HBV母婴传播提供理论依据。方法选取2021年10月至2023年10月期间在新疆生产建设兵团第一师阿拉尔医院产科建档及生产的HBsAg阳性孕妇为研究对象,通过磁微粒化学发光法检测孕妇五项HBV血清标志物包括测HBsAg和乙肝病毒表面抗体(HBsAb)、乙肝病毒e抗原(HBeAg)、乙肝病毒e抗体(HBeAg)以及乙肝病毒核心抗体(HBcAb),并利用荧光定量PCR检测HBV-DNA载量,分析HBV-DNA载量以及孕妇HBV感染模式对新生儿的影响。结果共纳入145例HBsAg阳性孕妇,HBV感染模式以感染模式Ⅱ[HbsAg(+)、HBeAb(+)和HBcAb(+)]为主,占62.76%。HBV-DNA阳性(>0.5×10^(3)IU/mL)阳性率为63.45%(92/145),不同HBV感染模式的HBsAg阳性孕妇HBV-DNA阳性率及载量分布情况比较差异有统计学意义(χ^(2)=16.532、64.367,P<0.05),主要表现为感染模式Ⅰ比例随HBV-DNA载量升高而增高。同时,HBV-DNA阳性组随HBeAg浓度升高而比例增高,而HBV-DNA阴性组正好相反,Spearman相关分析表明HBsAg阳性孕妇的HBeAg浓度与HBV DNA载量呈现明显正相关性(r=0.327,P<0.05)。不同HBV感染模式的HBsAg阳性孕妇的新生儿脐带血HBV阳性率比较差异有统计学意义(χ^(2)=16.851,P=0.002),同时HBsAg阳性孕妇的新生儿脐带血HBV阳性率随着HBV-DNA载量增高而明显增高,差异有统计学意义(χ^(2)=15.062,P=0.005)。结论HBsAg阳性孕妇血清标志物模式与HBV-DNA病毒载量密切相关,产前筛查对孕产妇及新生儿的乙肝预防及干预有重要意义,是母婴传播防控的重点。

聚乙二醇干扰素α-2b联合核苷(酸)类似物治疗对慢性乙型肝炎患者的HBsAg清除率影响分析

目的探讨慢性乙型肝炎(Chronic Hepatitis B Virus,CHB)患者采用聚乙二醇干扰素α-2b(Peg Interferonα-2b,Peg-IFN-α-2b)联合核苷(酸)类似物(Nucleoside Analogues and Nucleotide Analogues,NAs)治疗对乙肝表面抗原(Hepatitis B Surface Antigen,HBsAg)清除率的影响。方法回顾性选取2019年6月—2022年6月厦门大学附属第一医院收治的148例CHB患者的临床资料,按照治疗方法的不同分成研究组(n=74)与对照组(n=74),对照组采用NAs治疗,研究组采用Peg-IFN-α-2b联合NAs治疗,比较两组患者HBsAg血清转阴率与转换率、乙肝病毒脱氧核糖核酸含量、肝功能指标、血清炎症因子水平。结果治疗12个月后,研究组HBsAg血清转阴率与转换率分别为35.14%、27.03%均高于对照组,差异有统计学意义(χ^(2)=17.995、17.299,P均<0.05)。治疗12个月后,两组患者乙肝病毒脱氧核糖核酸含量均下降,且研究组低于对照组,差异有统计学意义(P均<0.05)。两组患者谷草转氨酶、谷丙转氨酶均下降,且研究组低于对照组,差异有统计学意义(t=7.713、2.089,P均<0.05)。两组患者白细胞介素-6、肿瘤坏死因子-α水平均下降,且研究组低于对照组,差异有统计学意义(t=10.820、7.032,P均<0.05)。结论CHB患者采用Peg-IFN-α-2b联合NAs治疗,可提高HBsAg血清转阴率与转换率,降低HBV-DNA含量,降低肝功能指标,降低血清炎症因子指标。

血清HBsAg、HBV RNA、GGT及GPR联合检测对慢性HBV感染自然史的诊断价值

目的探讨慢性乙型肝炎病毒(HBV)感染自然史各期患者血清乙型肝炎病毒表面抗原(HBsAg)、乙型肝炎病毒核糖核酸(HBV RNA)、γ-谷氨酰转肽酶(GGT)、γ-谷氨酰转肽酶/血小板比值(GPR)水平变化及联合检测对慢性HBV感染自然史分期的诊断价值。方法选取2020年11月至2023年12月在昆明市第三人民医院就诊的未经抗病毒治疗的172例慢性HBV感染患者为研究对象,根据HBV感染进程分为HBeAg阳性慢性HBV感染(EPI)组(n=77)、HBeAg阳性CHB(EPH)组(n=42)、HBeAg阴性慢性HBV感染(ENI)组(n=26)、HBeAg阴性CHB(ENH)组(n=27)。比较各组患者血清HBsAg、HBV RNA、GGT、GPR水平差异,绘制受试者工作特征(ROC)曲线探究血清HBsAg、HBV RNA、GGT、GPR联合检测对慢性HBV感染自然史中EPH期和ENH期的诊断价值。结果4组患者血清HBsAg、HBV RNA、GGT、GPR水平比较,差异均有统计学意义(P<0.05)。血清HBsAg、HBV RNA、GGT、GPR联合检测诊断EPH期和ENH期的ROC曲线下面积(AUC)分别为0.869和0.836,敏感度和特异度分别为76.19%、59.26%和84.42%、96.15%。结论血清HBsAg、HBV RNA、GGT、GPR联合检测对慢性HBV感染自然史诊断有较高的准确性和低误诊率,有望取代传统的有创检查,对于慢性HBV感染自然史各期患者的精准诊断及个体化治疗策略的制订发挥着重要的临床意义。

慢性乙型肝炎患者甲状腺激素水平与HBsAg水平及病情严重程度的相关性分析

目的 分析慢性乙型肝炎(CHB)患者甲状腺激素水平与乙型肝炎表面抗原(HBsAg)水平及病情严重程度的相关性。方法 选择115例2021年7月—2023年7月在中江县人民医院进行治疗CHB患者为研究对象,设为观察组,另选同期于我院体检中心体检的100名健康者将其纳入对照组,比较两组甲状腺激素[游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)、促甲状腺激素(TSH)]水平及HBsAg水平,观察不同病情严重程度、不同肝硬化病理分期患者以上指标水平,另采用Pearson相关性分析以上指标与病情严重程度、肝硬化病理分期的相关性。结果 与对照组血清FT3、FT4、TSH、HBsAg水平[(4.95±0.61)pmol/L、(17.56±2.34)pmol/L、(2.94±0.31)μIU/mL、(0.04±0.01)IU/mL]相比,观察组FT3、FT4、TSH[(3.75±0.42)pmol/L、(15.41±2.13)pmol/L、(2.67±0.45)μIU/mL]明显下降,HBsAg水平(3.11±1.12)IU/mL显著升高(t=16.973、7.051、5.048、27.401,P<0.05);轻度CHB患者FT3、FT4、TSH水平[(4.15±0.51)pmol/L、(16.24±2.08)pmol/L、(2.23±0.65)μIU/mL]高于中度患者[(3.73±0.49)pmol/L、(15.23±2.31)pmol/L、(1.94±0.52)μIU/mL],中度患者FT3、FT4、TSH水平高于重度患者[3.34±0.37)pmol/L、(14.19±2.04)pmol/L、(1.66±0.67)μIU/mL],三组患者HBsAg水平[(2.45±0.63)IU/mL、(2.84±0.75)IU/mL、(3.23±1.01)IU/mL]逐渐升高(F=25.761、7.604、7.513、8.039,P<0.05);肝纤维化S1患者的血清FT3、FT4、TSH水平[(4.06±0.61)pmol/L、(16.54±2.23)pmol/L、(2.62±0.54)μIU/mL]高于S2[(3.75±0.53)pmol/L、(15.17±2.21)pmol/L、(2.17±0.62)μIU/mL],S2高于S3[(3.37±0.49)pmol/L、(14.02±2.45)pmol/L、(1.83±0.42)μIU/mL],S3高于S4[(2.68±0.47)pmol/L、(12.81±2.07)pmol/L、(1.36±0.57)μIU/mL],四组HBsAg水平[(1.85±0.21)IU/mL、(2.09±0.57)IU/mL、(2.64±0.62)IU/mL、(3.08±0.97)IU/mL]逐渐升高(F=35.438、11.509、23.256、17.201,P<0.05);相关性分析显示,甲状腺激素水平与CHB病情严重程度、CHB肝纤维化严重程度呈负相关(r=-0.458、-0.651、-0.715、-0.694、-0.597、-0.712,P<0.05),HBsAg水平与CHB病情严重程度、CHB肝纤维化严重程度呈正相关(r=0.531、0.673,P<0.05)。结论 CHB患者甲状腺激素水平与HBsAg水平及病情严重程度关系密切,联合检测FT3、FT4、TSH及HBsAg可有效评估病情严重程度、预测纤维化进程。

瞬时弹性成像及血清HBsAg、HBV DNA联合评估乙型肝炎肝纤维化程度的价值

目的探讨瞬时弹性成像及血清乙型肝炎表面抗原(HBsAg)、乙型肝炎病毒DNA(HBV DNA)联合评估乙型肝炎肝纤维化程度的价值。方法2019年2月-2023年4月淮南朝阳医院收治77例慢性乙型肝炎患者,患者均接受肝脏穿刺活检判定肝纤维化分期,其中S0期14例、S1期20例、S2期21例、S3期13例、S4期9例。采用Mindray Hepatus 5检测仪检测肝硬度值,检测血清HBsAg、HBV DNA水平。结果S0~S1期、S2期、S3期、S4期肝硬度值分别为(6.02±1.41)、(9.11±1.46)、(11.26±1.38)、(13.05±1.59)kPa,S4期肝硬度值大于S3期,S3期肝硬度值大于S2期,S2期肝硬度值大于S0~S1期(P<0.05);S0~S1期、S2期、S3期、S4期HBsAg水平分别为(216.81±42.09)、(142.68±35.17)、(53.61±11.54)、(26.51±8.14)IU/mL,S0~S1期、S2期、S3期、S4期HBV DNA分别为(1.14××10^(6)±1.79×10^(5))、(1.06××10^(6)±1.54×10^(5))、(9.61×10^(5)±1.39×10^(5))、(8.47×10^(5)±1.33×10^(5))IU/mL,S0~S1期HBsAg水平高于S2期,S2期HBsAg水平高于S3期,S3期HBsAg水平高于S4期,S0~S1期HBV DNA水平高于S3期和S4期,S2期HBV DNA水平高于S4期(P<0.05);经ROC分析,肝硬度值与血清HBsAg、HBV DNA评估肝纤维化程度≥S2期的ROC曲线下面积分别为0.829(95%CI:0.746~0.912)、0.747(95%CI:0.678~0.816)、0.723(95%CI:0.624~0.821),最佳截断值分别为7.362 kPa、148.306 IU/mL、1.092××10^(6) IU/mL,敏感度分别为0.774、0.648、0.679,特异度分别为0.920、0.837、0.863,三项指标联合诊断的曲线下面积为0.907(95%CI:0.861~0.953),敏感度和特异性分别为0.910、0.958,P<0.05。结论瞬时弹性成像及血清HBsAg、HBV DNA单独评估肝纤维化程度≥S2期的慢性乙型肝炎患者均有较好的价值,联合评估时可进一步提高灵敏度和特异度。

无锡地区HBsAg-/HBV DNA+献血人群HBcrAg检出特点分析

目的分析新型血清标志物乙型肝炎核心相关抗原(HBcrAg)在无锡地区HBsAg-/HBV DNA+献血人群中的检出特点。方法通过电话追踪随访了37名既往HBsAg-/HBV DNA+献血者并获得其血清,采用电化学发光法和实时荧光定量PCR核酸筛检出22例HBsAg-/HBV DNA+献血者血清作为OBI组进行HBcrAg酶联免疫吸附法检测。挑选出20名经2遍酶免和1遍核酸筛检的健康献血者的血清作为健康对照组,20例经无锡第五人民医院临床诊断为慢性乙型肝炎患者血清作为实验的CHB组,分别进行HBcrAg酶联免疫吸附法检测;并对OBI组进行HBcrAg与HBeAb、HBcAb、ALT、HBV DNA的相关性分析。结果37份献血者标本经化学发光法检测HBsAg和核酸筛查,检出22份HBsAg-/HBV DNA+标本即OBI组,检出率59.46%。OBI组与健康对照组、CHB组血清的HBcrAg表达含量分别是(0.92±0.13)ng/mL、(0.47±0.09)ng/mL、(1.14±0.23)ng/mL(P<0.05),OBI组与CHB组的HBcrAg表达均高于健康对照组(P<0.05)。OBI组的HBcrAg与HBeAb、HBcAb、ALT、HBV DNA指标均无相关性(P>0.05)。结论OBI组与CHB组的HBcrAg表达均高于健康对照组,其血清HBcrAg在一定程度上与HBeAb、HBcAb、ALT、HBV DNA无相关性,HBcrAg在筛查HBsAg-/HBV DNA+献血者中具有较好的应用前景。