The Relationship between Intrahepatic Distribution of Hepatitis B Virus Core Antigen and Serum ALT, HBV DNA Levels and HBeAg Status

Objective The clinical significance of differential distribution of hepatitis B virus(HBV)nucleocapsid antigen in hepatocytes remains unknown.The goal of this study is to determine the relationship between distinct HBV core antigen distribution pattern and alanine transaminase(ALT),liver histological inflammatory activity grades,serum HBeAg status and HBV DNA level.Methods Total of 958 cases with chronic hepatitis B were recruited into this study.Liver function tests,serum HBV DNA level,serological HBV markers and liver immunohistochemistry were examined according to the conventional instructions.Chi Square tests were performed to analyze the differences among these groups.Results It was found that 552(58%)cases were tested positive for HBV core antigen by immunohistochemical staining.Cytoplasmic hepatitis B core antigen(HBcAg)expression correlated with ALT level and serum HBV DNA and liver inflammatory activity scores,however,nuclear HBcAg expression in hepatocytes was associated with normal ALT level,lower liver inflammatory activity score and higher serum HBV DNA level and rate of HBeAg positivity.Both nuclear and cytoplasmic HBcAg expression in hepatocytes associated with a middle ALT level and liver inflammatory activity score,higher rate of serum detectable HBeAg and a higher HBV DNA level.However,undetectable core antigen was related to a lower ALT level and histological inflammatory activity grade,lower positive HBeAg rate and HBV DNA level.Conclusions Undetectable liver HBcAg is associated with HBV clearance,ALT normalization and hepatitis B e antigen(HBeAg)seroconversion,and cytoplasmic HBcAg expression associated with higher hepatic inflammatory activity.However,nuclear HBcAg expression correlates with immune tolerance characterized with normal ALT and lower liver inflammatory activity,higher HBV replication level and higher rate of HBeAg positivity.

慢性乙型肝炎患者血清乙型肝炎病毒RNA对核苷(酸)类似物治疗后HBeAg清除和血清转化的预测价值

目的探讨慢性乙型肝炎(CHB)患者血清乙型肝炎病毒(HBV)RNA对核苷(酸)类似物(NA)治疗后乙型肝炎病毒e抗原(HBeAg)清除和血清转化的预测价值。方法收集2017年2月12日至2019年2月21日在山东中医药大学附属威海医院首次接受NA单药治疗的178例CHB患者的血清样本。采用实时荧光定量PCR法定量检测基线和NA治疗后血清HBV RNA水平。结果HBeAg清除组和血清转化组患者基线、治疗6个月时和12个月时的血清HBV RNA水平分别显著低于未清除组和未转化组(P<0.001)。随访期间,基线HBV RNA水平较低的患者累积HBeAg清除率(Log Rankχ^(2)=11.282,P=0.001)或血清转化率(Log Rankχ^(2)=10.739,P=0.001)高于较高水平的患者。经Cox回归模型分析,基线、治疗6个月和12个月时的血清HBV RNA是CHB患者HBeAg清除和血清转化的独立影响因素(P<0.05)。基线血清HBV RNA水平预测HBeAg清除和血清转化的ROC曲线下面积(AUC)分别为0.808(95%CI:0.743~0.872)和0.824(95%CI:0.763~0.885);治疗6个月时的AUC分别为0.830(95%CI:0.765~0.894)和0.732(95%CI:0.657~0.808);治疗12个月时的AUC分别为0.737(95%CI:0.641~0.833)和0.757(95%CI:0.671~0.842)。基线血清HBV RNA联合6个月时HBV RNA下降程度预测AUC分别为0.856(95%CI:0.795~0.917)和0.864(95%CI:0.802~0.926);联合12个月时HBV RNA下降程度预测AUC分别为0.881(95%CI:0.826~0.936)和0.848(95%CI:0.784~0.911)。结论CHB患者血清HBV RNA水平对NA治疗后HBeAg清除和血清转化具有较高的预测价值,提示HBV RNA水平可以帮助识别无反应者并促使考虑联合治疗。

IFNα-2b治疗323例HBeAg阳性慢性乙型肝炎的效果

目的 探讨IFNα-2b抗病毒治疗乙型肝炎e抗原(HBeAg)阳性慢性乙型肝炎(CHB)患者的效果。方法回顾性分析2010年1月至2014年1月就诊于南昌大学第二附属医院并接受IFNα-2b治疗的323例HBeAg阳性CHB患者的临床资料,按丙氨酸氨基转移酶(ALT)水平将其分为3组:ALT<2×ULN(A1组,n=111)、2×ULN≤ALT≤5×ULN(A2组,n=111)以及ALT>5×ULN(A3组,n=101)。观察临床疗效及不良反应,并比较3组间的抗病毒效果。结果 在停药时及停药后第12、24、48、72、96、144、192、240周,323例患者的HBV-DNA阴转率分别为39.9%、40.2%、39.0%、36.2%、34.1%、33.4%、31.3%、30.7%、30.7%;HBsAg阴转率分别为6.2%、6.2%、6.2%、5.9%、5.9%、5.9%、5.6%、5.6%、5.6%;HBeAg血清学转换率分别为28.2%、31.0%、32.8%、34.4%、33.7%、33.1%、32.8%、32.5%、31.6%。在各随访时间点,3组患者的HBV-DNA阴转率和HBeAg血清学转换率比较,A3组显著高于A2组,A2组显著高于A1组(P<0.05);3组患者的HBsAg阴转率比较,差异无统计学意义(P>0.05)。323例患者均出现发热及类流感样症状,238例(73.7%)出现白细胞及中性粒细胞降低,35例(10.8%)甲状腺功能异常,5例(1.5%)斑秃,1例(0.3%)睡眠障碍,经过密切观察和对症处理后,患者均顺利完成疗程,各指标均基本正常。结论 IFNα-2b治疗HBeAg阳性CHB患者在停药时及停药后随访期间均表现出较好的效果,大多数患者可耐受IFNα-2b的不良反应。IFNα-2b的抗病毒效果可能与ALT水平有关。

HBeAg阳性ALT正常不确定期患者肝组织纤维化程度及影响因素分析

目的:分析乙型肝炎e抗原(HBeAg)阳性丙氨酸氨基转移酶(ALT)正常不确定期患者肝脏组织纤维化程度,为HBeAg阳性ALT正常不确定期患者的病情判断提供依据。方法:选取2017年1月至2021年12月HBeAg阳性ALT正常乙型肝炎病毒载量(HBV DNA)水平低于2×10^(7)IU/ml且高于20 IU/ml者作为研究对象,对该类患者进行肝组织病理学检查,并收集患者年龄、性别、感染HBV时间、肝功能、乙型肝炎表面抗原(HBsAg)水平、HBV DNA载量、基因型、门静脉内径、脾静脉内径、脾脏厚度等,Logistic回归分析患者肝组织纤维化的影响因素,受试者工作特征(ROC)曲线及相关参数评价其效能。结果:178例患者中,Scheuer法分期:S0期6例(3.4%),S1期67例(37.6%),S2期83例(46.6%),S3期14例(7.9%),S4期8例(4.5%),纤维化程度≥S2期105例(59.0%)。Logistic回归分析肝组织显著纤维化与感染时间(OR=1.101,95%CI=1.000~1.212;P=0.049)、HBV DNAlg(OR=1.280,95%CI=1.023~1.600;P=0.031)、门静脉内径(OR=1.611,95%CI=1.100~2.360;P=0.014)和脾脏厚度(OR=1.276,95%CI=1.107~1.469;P=0.001)独立相关,ROC曲线下面积(AUC)分别为0.67、0.62、0.70、0.67,天门冬氨酸氨基转移酶/血小板(APRI)和肝纤维化4因子指数(FIB-4)的AUC分别为0.68、0.57。结论:HBeAg阳性ALT正常不确定期患者中,有相当比例的患者纤维化程度≥S2,具有抗病毒治疗的指征。感染时间、HBV DNA、门静脉内径和脾脏厚度可能对预测其肝组织显著纤维化有一定的临床价值。

HBeAg/HBeAb双阳性慢性乙型肝炎患者血清HBV RNA的变化及临床转归分析

目的探讨HBeAg/HBeAb双阳性慢性乙型肝炎(CHB)患者血清HBV RNA的变化及临床转归分析。方法选取2020年6月至2022年8月诊治的102例HBeAg/HBeAb双阳性CHB患者作为研究对象,设立为双阳组,同期选取51例HBeAg阳性、HBeAb阴性的CHB患者和52例HBeAg阴性、HBeAb阳性的CHB患者设立为对照1组和对照2组,对比血清HBV RNA变化。根据治疗方法不同将双阳组分为干扰素组(予以干扰素治疗,n=52)和恩替卡韦组(予以恩替卡韦治疗,n=50),对比HBeAg、HBeAb浓度及HBeAg转阴,HBeAb仍阳性、HBeAg和HBeAb同时转阴、HBeAg未转阴,HBeAb仍阳性占比。结果双阳组的HBV RNA水平均高于对照1、2组(P<0.05)。治疗前,干扰素组和恩替卡韦组的HBeAg、HBeAb、HBV RNA比较,差异无统计学意义(P>0.05),治疗后,干扰素组的HBeAg、HBeAb、HBV RNA低于恩替卡韦组(P<0.05)。干扰素组的HBeAg转阴,HBeAb仍阳性占比高于恩替卡韦组,而HBeAg未转阴,HBeAb仍阳性占比低于恩替卡韦组(P<0.05)。2组HBeAg和HBeAb同时转阴占比比较,差异无统计学意义(P>0.05)。ROC曲线分析显示,HBV RNA预测CHB患者HBeAg/HBeAb双阳性和临床转归不良的AUC值分别为(0.936、0.954,P<0.05);敏感度分别为100.00%、93.10%;特异度分别为88.70%、76.70%。结论HBV RNA在HBeAg/HBeAb双阳性CHB患者中呈高表达趋势,观察其水平变化有助于为预测临床转归提供指导。

不同HBeAg结果HBV感染患者临床指标与肝脏病理特征的关联性分析

目的:探讨不同HBeAg结果乙型肝炎病毒(HBV)感染患者临床指标与肝脏病理特征的关联性。方法:选取2021年1月—2022年2月某院收治的103例乙肝病毒感染患者为研究对象,根据血清HBeAg结果将患者分为HBeAg阳性组(n=39)和HBeAg阴性组(n=64)。分析影响2组患者肝脏炎症程度和纤维化程度的危险因素,绘制ROC曲线,分析CHE水平对不同HBeAg结果的HBV感染患者肝脏炎症和纤维化程度的预测效能。结果:HBeAg阳性组年龄、ALB、CHE水平低于HBeAg阴性组,中重度炎症比例高于HBeAg阴性组,差异有统计学意义(P<0.05)。纤维化分级≥2、CHE水平降低为HBeAg阴性患者发生中重度肝炎的独立危险因素。炎症分级≥2级是HBeAg阴性患者发生中重度肝脏纤维化的独立危险因素。血清CHE水平预测HBeAg阳性患者肝组织炎症程度和纤维化程度的曲线下面积(AUC)分别为0.820和0.900,敏感度分别为83.3%和79.3%,特异度分别为71.4%和90.0%。血清CHE水平预测HBeAg阴性患者肝脏炎症程度和纤维化程度的AUC分别为0.723和0.597,敏感度分别为82.2%和29.4%,特异度分别为57.9%和100%。结论:不同HBeAg结果的HBV感染者ALB、CHE水平及炎症程度不同;炎症程度越重的HBeAg阴性患者越容易发生中重度肝纤维化,反之亦然;血清CHE水平可作为预测HBV感染者肝脏炎症和纤维化程度的敏感指标。

HBeAg诱导的免疫激活和免疫抑制在慢性乙型肝炎中的作用

HBV感染诱导的慢性乙型肝炎是导致肝硬化和肝癌的重要危险因素。半个世纪前,HBeAg在HBV感染者血清中首次被发现,尽管HBeAg并不参与HBV在肝细胞中的感染或复制,但其已被证实可干扰宿主先天性和适应性免疫反应,在慢性HBV感染的过程中发挥着重要的免疫激活和免疫抑制作用。HBV对于感染的肝细胞并没有细胞毒性,免疫应答介导的抗病毒作用和炎症反应决定HBV是否被清除或者诱导肝脏炎症相关疾病。因此,本文对HBeAg的形成及其在慢性HBV感染中引起的免疫激活和免疫抑制机制进行综述,重点论述HBeAg对先天免疫和适应性免疫细胞所引起的不同免疫效应,阐述了其诱导免疫反应的两面性,并探讨HBeAg在慢性HBV感染不同阶段间的转换作用。

Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

无创方法诊断HBeAg阳性慢性乙型肝炎患者肝内炎症反应程度

目的建立由简单常规实验数据组成的模型,以预测HBeAg阳性且丙氨酸氨基转移酶(ALT)≤2倍正常上限的慢性乙型肝炎(CHB)患者的肝脏炎症反应程度。方法选取2019年4月1日至2021年5月8日151例HBeAg阳性且ALT≤2倍正常上限的CHB患者作为研究对象,根据肝脏病理检查结果分为轻度炎症反应[肝组织炎症分级(G)G0~1]组和中度炎症反应(G≥2)组,采用多因素Logistic回归分析CHB患者发生中度炎症反应的独立危险因素并建立诊断模型。结果53.0%(80/151例)的研究对象出现G≥2。G≥2组ALT、天门冬氨酸氨基转移酶(AST)水平均明显高于G0~1组,胆碱酯酶(ChE)、前蛋白比(PA)、HBsAg均明显低于G0~1组,差异均有统计学意义(P<0.05)。ALT、AST与G分级均呈弱正相关(r=0.212、0.303,P<0.05),ChE、PA、HBsAg与G分级均呈弱负相关(r=-0.371、-0.330、-0.173,P<0.05)。高水平AST、低水平PA、低水平logChE为CHB患者发生中度炎症反应的独立危险因素(P<0.05)。模型CPA对预测发生G≥2的受试者工作特征曲线下面积为0.842(95%CI:0.741~0.935)。当CPA≤0.3,其排除G≥2的阴性预测值为84.21%;当CPA≥0.6时,CPA诊断发生G≥2的阳性预测值为84.00%。结论AST、PA和logChE与HBsAg阳性且ALT≤2倍正常上限的CHB患者的肝内炎症反应程度相关。CPA对发生G≥2具有较好的诊断效能,且该模型涉及的指标简单易得,适合临床推广使用。

Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation

BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.

Fasciola worm and egg-derived antigens:Exploring their diagnostic potential for urogenital schistosomiasis in resource-limited endemic regions

Objective:To evaluate the immunodiagnostic potential of crude Fasciola gigantica-worm(FWA)and egg antigen(FEA)in detecting anti-Schistosoma(S.)haematobium antibodies in sera and urine samples.Methods:This is a cross-sectional diagnostic study.Employing an indirect ELISA,antibodies against these antigens were assessed in samples from infected and non-infected individuals in both schistosomiasis endemic(NE)and non-endemic(NNE)areas,using microscopy as the diagnostic standard.Results:FWA-sera exhibited excellent diagnostic accuracy with an area under the curve(AUC)of 0.957,a sensitivity of 93.75%,and a specificity of 85.42%for discriminating between infected and non-infected individuals in non-endemic areas.FWA-urine also demonstrated robust performance,achieving AUC>0.95,sensitivity>97.0%,and specificity>85.0%in both NE and NNE categories.Notably,S.haematobium-specific antibody levels against FWA were significantly elevated in infected individuals in both endemic and non-endemic areas.FEA-sera exhibited outstanding diagnostic performance with sensitivity exceeding 90%and an AUC of 0.968 in non-endemic samples but not in FEA-urine.Conclusions:FWA-based ELISAs,applicable to both sera and urine,emerge as promising tools for S.haematobium diagnosis in resource-limited settings,offering advantages of high sensitivity and specificity with shared antigens with Fasciola.The superior diagnostic metrics of urine samples suggest their potential as a non-invasive biological sample for diagnostic purposes.

The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

Prostate cancer with elevated free prostate-specific antigen density:A case report

BACKGROUND Prostate cancer is the second most common cancer among men worldwide,and prostate-specific antigen(PSA)is often used in clinical practice to screen for prostate cancer.Normal total PSA(tPSA)level initially excludes prostate cancer.Here,we report a case of prostate cancer with elevated free PSA density(fPSAD).CASE SUMMARY A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy,and the postoperative pathological results showed acinar adenocarcinoma of the prostate.The patient is currently undergoing endocrine chemotherapy.CONCLUSION We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

双歧杆菌三联活菌联合恩替卡韦对乙型肝炎肝硬化患者ALT水平和HBeAg血清学转换率及HBV-DNA载量的影响

目的 观察双歧杆菌三联活菌联合恩替卡韦对乙型肝炎肝硬化患者和丙氨酸氨基转移酶(ALT)水平、乙型肝炎E抗原(HBeAg)血清学转换率及HBV-DNA载量的影响。方法 选取2017年3月—2019年3月湖北科技学院附属浠水医院收治的乙型肝炎肝硬化患者122例,根据随机数字表法分为试验组和对照组,各61例。对照组予恩替卡韦分散片治疗,试验组在对照组基础上予双歧杆菌三联活菌胶囊治疗,2组均治疗6个月。比较2组肝功能指标[ALT、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)]、HBeAg血清学转换率、HBV-DNA载量、生活质量评分、肠道菌群分布及不良反应。结果 治疗6个月后,2组ALT、AST、TBil水平较治疗前降低,且试验组低于对照组(P<0.01)。治疗12、24周,2组HBeAg血清学转换率比较差异无统计学意义(P>0.05);治疗48周,试验组HBeAg血清学转换率高于对照组(P<0.05)。治疗6个月后,2组HBV-DNA载量较治疗前降低,且试验组低于对照组(P<0.01);2组生理功能、情感职能、精神健康、躯体疼痛评分组内、组间比较差异无统计学意义(P>0.05);2组生理职能、社会功能、活力及总体健康评分较治疗前升高,且试验组生理职能、活力及总体健康评分高于对照组(P<0.05或P<0.01),社会功能评分组间比较差异无统计学意义(P>0.05);2组乳杆菌、双歧杆菌高于治疗前,肠杆菌、肠球菌、梭菌低于治疗前,且试验组变化幅度大于对照组(P<0.01)。试验组与对照组不良反应总发生率比较差异无统计学意义(8.20%vs. 6.56%,P=1.000)。结论 双歧杆菌三联活菌联合恩替卡韦治疗乙型肝炎肝硬化,可改善患者ALT、AST、TBil水平,提高HBeAg血清学转换率,降低HBV-DNA载量,改善患者生活质量,且不会明显增加不良反应。

育龄期女性孕期口服富马酸替诺福韦二吡呋酯片行母婴阻断HBeAg转换率的研究

目的 观察育龄期女性孕期予富马酸替诺福韦二吡呋酯(TDF)行母婴阻断的乙型肝炎e抗原(HBeAg)转换率。方法 收集2019年1月—2022年6月赣州市第五人民医院收治的HBeAg阳性、高HBV-DNA载量的妊娠中晚期孕妇(孕24~28周)病例数据,按照纳入标准和排除标准进行筛选出60例有效病例,根据随机数字表法分为TDF组和对照组,每组30例。2组均采取常规保肝治疗与抗病毒治疗,在此基础上TDF组采用富马酸替诺福韦二吡呋酯片治疗。比较2组孕妇治疗4、8、12周后与产后4周的HBeAg转换率情况,孕妇治疗前与治疗4、8、12周后及产后4周HBV-DNA浓度、乙肝血清标志物[乙型肝炎表面抗原(HBsAg)、乙型肝炎表面抗体(HBsAb)]、肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]及肌酐水平。结果 TDF组在治疗4、8、12周后与产后4周的HBeAg转换率均高于对照组(P<0.05);治疗4、8、12周后与产后4周,2组HBV-DNA浓度、HBsAg、HBsAb水平较治疗前下降,且TDF组低于对照组(P均<0.01),而2组ALT、AST及肌酐水平治疗前后比较差异均无统计学意义(P>0.05)。结论 育龄期女性孕期行母婴阻断治疗时,在常规治疗基础上,口服富马酸替诺福韦二吡呋酯片可明显提高在治疗4、8、12周后与产后4周的HBeAg转换率,对于降低HBV-DNA浓度、乙肝血清标志物HBsAg、HBsAb效果显著,而对于孕妇肝功能、肾功能影响不明显。

Human leukocyte antigen compatibility and incidence of donorspecific antibodies in pediatric liver transplant recipients

BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft longevity.While substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains limited.AIM To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.METHODS A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December 2023.Only patients who survived for>30 days after LT with at least one DSA analysis were included.DSA classes I and II and cross-matches were analyzed.The presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 MFI.Rejection episodes were confirmed by liver biopsy.RESULTS Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to recipients.Pre-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]months.Biopsyproven rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 Liver biopsies.The median time to rejection was 7.8(IQR:5.7-12.8)months.The presence of dnDSA was significantly associated with rejection(36%vs 3%,P<0.001).The rejection-free survival rates at 12 and 24 months were 76%vs 100%and 58%vs 95%for patients with dnDSA anti-DQ vs those without,respectively.CONCLUSION Our findings highlight the importance of incorporating DSA assessment into pre-and post-transplantation protocols for pediatric LT recipients.Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗HBeAg阳性慢性乙肝的临床效果

目的观察聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗乙肝e抗原(HBeAg)阳性慢性乙肝的临床效果。方法选取2019年1月—2023年1月厦门市第三医院收治的HBeAg阳性慢性乙肝患者80例,按随机数字表法分为联合组(n=40)和单药组(n=40)。单药组予替诺福韦二吡呋酯治疗,联合组在单药组基础上予聚乙二醇干扰素α-2b治疗,2组均持续治疗6个月。比较2组HBeAg及乙肝病毒脱氧核糖核酸(HBV-DNA)转阴率,治疗前后肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)]、血清炎性因子[肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10]、肝纤维化指标[透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)]及不良反应。结果与单药组比较,联合组HBeAg及HBV-DNA转阴率均更高(χ^(2)=10.208,P=0.001;χ^(2)=4.507,P=0.034);与治疗前比较,治疗6个月后,2组AST、ALT、TBil、TNF-α、IL-6、IL-10、HA、PCⅢ、LN水平均降低,且联合组低于单药组(P<0.01)。联合组与单药组不良反应总发生率比较差异不明显(12.50%vs.7.50%,χ^(2)=0.139,P=0.709)。结论HBeAg阳性慢性乙肝患者应用聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗效果确切,有助于提高HBeAg、HBV-DNA转阴率,改善肝功能,减轻炎性反应及肝纤维化程度,且安全性较高。

Technetium-99m-methylene diphosphonate single photon emission computed tomography/computed tomography combined with prostate-specific antigen/free prostate-specific antigen ratio for bone metastasis of prostate cancer

BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.

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.