Chronic active Epstein-Barr virus infection treated with PEGaspargase: A case report

BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV(CAEBV),and hematopoietic stem cell transplantation is the only effective treatment.We here report a CAEBV patient treated with PEG-aspargase,who achieved negative EBV-DNA.CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017.EBV-DNA was positive with a high copy number.She was diagnosed with chronic active EB virus infection.PEGaspargase was administered at a dose of 1500 U/m2 at a 14-d interval,resulting in eradication of EBV for more than 6 mo.The effect of PEG-aspargase in this patient was excellent.CONCLUSION A chemotherapy regimen containing PEG-aspargase for CAEBV may be further considered.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.

Clinical analysis and follow-up study of chronic active Epstein-Barr virus infection in 53 pediatric cases

Background Chronic active Epstein-Barr virus infection （CAEBV） has been previously reported to be sometimes associated with an aggressive clinical course. The characteristics of CAEBV in Mainland Chinese pediatric patients are largely unreported. The main aims of this survey were to recognize the clinical features of CAEBV in children and to explore its diagnostic criteria and risk factors. Methods A retrospective study was performed on 53 pediatric patients （36 boys and 17 girls） with CAEBV who were admitted to Beijing Children＇s Hospital between 2003 and 2007. All their medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory data and outcome were collected. Independent-samples t test was used for statistical analysis. Results The age at onset of CAEBV was from 2 months to 14.6 years （mean （5.3_＋3.3） years）. At the time of onset, 43.4% patients had an infectious mononucleosis-like symptom. Most patients exhibited intermittent fever （92.5%, 49/53）, hepatomegaly （81.1%, 43/53） and splenomegaly （77.4%, 41/53）. Life-threatening complications including hemophagocytic syndrome （24.5%,13/53）, interstitial pneumonia （24.5%, 13/53）, hepatic failure （15.1%, 8/53） and malignant lymphoma （11.3%, 6/53） were also observed. The serum EBV DNA level in 23 patients with CAEBV was in the range of 5.05×10^2-4.60×10^6 copies/ml with a mean value of 103.7 copies/ml. Many patients with CAEBV generally had continuous symptoms during the observational period. Eleven out of 42 patients （26.2%） died 7 months to 3 years after onset. Deceased patients were more likely to have had lower platelet counts and albumin levels than the living patients （P 〈0.05 for all comparisons）. Conclusions The study reveals that CAEBV in Chinese pediatric patients has a severe clinical course and prognosis is poor. Thrombocytopenia and decreases in albumin might potentially be risk factors for a poor prognosis. EBV loads should be measured and tissue should be stained on hybridization probes for EBV-encoded small RNA （EBER） if a patient presents with the known symptoms of CAEBV.

Haploidentical hematopoietic stem cell transplantation for pediatric patients with chronic active Epstein-Barr virus infection:a retrospective analysis of a single center

Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr virus infection(CAEBV).Methods Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital,Capital Medical University,from October 2016 to June 2020 were analyzed retrospectively.Data relating to the clinical manifestations,engraftment,and prognosis of the children were extracted from medical records.Results Twenty-five patients,including 16 males and 9 females,with an onset age of 5.0±2.6 years and a transplantation age of 6.9±2.9 years,were enrolled irnhis study.The mean time from diagnosis to transplantation was 3.8(2.0-40.2)months.The mean observation time was 19.0±12.0 months.Three patients received the reduced intensity conditioning regimen,and the remaining patients all received the modified myeloablative conditioning regimen.By the end of the follow-up,23 patients were characterized by disease-free survival(DFS),22 were characterized by event-free survival(EFS).and two died.One of the patients died of thrombotic microangiopathy(TMA),and another died of graft versus host disease(GVHD);this patient discontinued the treatment for economic reasons.The 3-year overall survival(OS)rate was estimated to be 92.0%±5.4%,and the 3-year EFS rate was estimated to be 87.4%±6.8%.All active patients survived after HSCT event-free.Acute GVHD degrees 1-3 were observed in ten patients(40.0%),and degree IV was observed in six(24.0%),who were all cured except for one patient.Chronic GVHD was observed in nine(36.0%),and most of these cases were mild.The incidence of TMA and veno-occlusive disease(VOD)was 28.0%and 4.0%.Conclusions Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation.Patients with active disease before HSCT also benefited from haplo-HSCT.Haplo-HSCT requires careful monitoring for complications,such as GVHD and TMA.Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.

Epstein-Barr virus:Silent companion or causative agent of chronic liver disease?

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.

Chronic Active Epstein–Barr Virus Infection

Chronic active Epstein-Barr virus(CAEBV)infection is a systemic Epstein–Barr virus(EBV)positive lymphoprolifetative disease characterized by fever,lymphadenopathy,splenomegaly,unusual pattern of antiEBV antibodies,and/or increased EBV genomes in affected tissues.Most cases are from Asia.So far,there is hardly any adult case reported from mainland of China.We herein presented a 33-year-old man with fever,facial erythema and rash,lymphadenopathy,lower limbs weakness,splenomegaly and liver lesion.EBV VCA,EA and EBNA were all positive.EBV DNA could be found in serum and PBMC.In situ hybridization of EBV encoded RNA in skin and liver biopsy was positive.Viral load in serum decreased under interferon alpha therapy.To our knowledge,it’s the first adult case reported from mainland of China.

Natural killer/T-cell lymphoma with intracranial infiltration and Epstein-Barr virus infection: A case report

BACKGROUND Because of atypical clinical symptoms,lymphoma is easily confused with infectious diseases.Extranodal nasal-type natural killer/T-cell lymphoma(NKTL)is more common,and there are few cases of eyelid site onset and intracranial infiltration,which increases the difficulty of diagnosis.This disease usually has a very poor prognosis and there are few reports of recovery.CASE SUMMARY A 3-year-old boy was admitted to our hospital due to an initial misdiagnosis of"eyelid cellulitis"and failed antibiotic treatment.He was characterized by fever,right eyeball bulging,convulsions,and abnormal liver function.His blood Epstein-Barr virus(EBV)DNA was positive(8.798×10^4 copies/mL),and remained positive for about half a year.The cranial imaging examination suggested a space-occupying lesion in the right eyelid,with the right temporal lobe and meninges involved.The boy underwent ocular mass resection.The pathological diagnosis was NKTL.He was diagnosed as having NKTL with intracranial infiltration,combined with chronic active EBV infection(CAEBV).Then he underwent systemic chemotherapy and intrathecal injection.The boy suffered from abnormal blood coagulation,oral mucositis,diarrhea,liver damage,and severe bone marrow suppression but survived.Finally,the tumor was completely relieved and his blood EBV-DNA level turned negative.The current follow-up has been more than 2 years and his condition is stable.CONCLUSION This case suggests that chemotherapy combined with intrathecal injection may have a good effect on intracranial infiltrating lymphoma and CAEBV,which deserves further study and discussion.

Mutations in hepatitis B virus core regions correlate with hepatocellular injury in Chinese patients with chronic hepatitis B

AIM: To elucidate the relationship between the frequency of core mutations and the clinical activity of hepatitis B virus (HBV)-related liver disease and to characterize the amino acid changes in the core region of HBV.METHODS: We studied 17 Chinese patients with chronic hepatitis B according to their clinical courses and patterns of the entire core region of HBV.RESULTS: Amino acid changes often appeared in the HBV core region of the HBV gene in patients with high values of alanine aminotransferase (ALT) or with the seroconversion from HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency sites that corresponded to HLA Ⅰ/Ⅱ restricted recognition epitopes reported by some investigators.CONCLUSION: The core amino acid changes of this study occur due to influence of host immune system. The presence of mutations in the HBV core region seems to be important for predicting the clinical activity of hepatitis B in Chinese patients.

Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein–Barr virus infection

Importance:Allogeneic hematopoietic stem cell transplantation(alloHSCT)is considered the only effective treatment for chronic active Epstein–Barr virus infection(CAEBV).The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear.Objective:To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning(MAC)regimen for children with CAEBV and also the factors affecting the outcomes.Methods:We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children’s Hospital,Capital Medical University from October 2016 to June 2021.Data related to the clinical manifestations,engraftment,and outcome were extracted from the medical records.Results:The cohort comprised 41 patients(24 males,17 females)with a median transplantation age of 92.6(60.4,120.7)months and a median follow-up time of 28.2(15.3,40.2)months.Four patients(9.8%)died,among which three died from primary disease relapse,and one died from grade IV acute graft-versus-host diseases(aGVHD)after stopping treatment.The 3-year overall survival(OS)and 3-year event-free survival(EFS)rates were 88.8%±5.4%and 85.0%±5.7%,respectively.The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis(HLH)and the patient without HLH(87.7%±6.8%vs.91.7%±8.0%,P=0.790;85.0%±6.9%vs.84.6%±10.0%,P=0.921),or among the patients with complete remission,partial remission,and activity disease before HSCT(all P>0.05).Multivariate analysis showed that grade III–IV aGVHD was a risk factor for mortality(Hazards ratio:11.65,95%confidence interval:1.00,136.06;P=0.050).Interpretation:Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV.This treatment benefits patients with HLH or active disease.Patients with Grade III–IV aGVHD may be associated with worse outcomes.

成人慢性活动性EB病毒感染患者的临床、病理特征及预后

目的研究成人慢性活动性EB病毒(EBV)感染患者的临床、病理特点及诊断、治疗方法和预后。方法回顾性收集甘肃省某医院2017年1月-2022年12月收治的8例成人慢性活动性EBV感染患者的临床及病理资料,分析其临床及组织病理特点、EBV相关检测结果,以及患者治疗、预后情况。结果8例慢性活动性EBV感染患者中,男性3例,女性5例;中位年龄21.5岁,自起病至确诊中位时间为7个月;以发热、血细胞(累及外周血两系或三系)减少、淋巴结及肝脾大为主要表现。血浆EBV核酸(DNA)定量均>1.0×103。EBV感染细胞分选结果显示,3例为T淋巴细胞感染,2例为NK细胞感染,3例为T淋巴细胞和NK细胞共同感染。8例患者骨髓细胞学检查均未见异型淋巴细胞,6例可见噬血细胞。流式细胞术(FCM)分型结果显示,8例患者均未检出异常细胞群,不表达髓细胞、B淋巴细胞、T淋巴细胞及NK细胞标记,T细胞受体(TCR)基因重排阳性率为37.5%(3例),病理组化显示大部分病例(6例,75.0%)表达CD3,部分病例表达CD4、CD8、CD56、TIA-1,EBER均为阳性。患者经治疗后生存率为50.0%(4例),随访时间为6~51个月,1年生存率为85.7%,中位生存时间为24个月。结论慢性活动性EBV感染患者临床表现多变,可出现致死性并发症,应尽早诊断,个体化治疗,降低患者病死率。

血清preS1水平与慢性乙型肝炎患者肝纤维化的关系及对癌变的诊断价值

目的分析血清乙型肝炎病毒(hepatitis B virus,HBV)前S1蛋白(precursor S1 protein,preS1)与慢性乙型肝炎(chronic hepatitis B,CHB)肝纤维化及癌变进展的相关性。方法对2019年10月—2021年10月期间在青海红十字医院接受检查的228例乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性慢性HBV感染者进行回顾性分析,其中CHB患者75例、肝硬化(liver cirrhosis,LC)患者93例(LC组)、肝细胞癌(hepatocellular carcinoma,HCC)患者60例(HCC组)。根据LC和HCC组肝组织活检分析肝脏炎症活动及肝纤维化程度。结果HCC组血清preS1水平[496.32(457.63,988.0)ng/mL]和LC组[338.72(247.93,554.61)ng/mL]血清preS1水平均显著高于CHB组[113.69(87.09,177.40)ng/mL],且差异具有统计学意义(P均<0.05)。HCC组血清preS1水平亦高于LC组(P=0.002)。经受试者工作特征曲线分析,血清preS1水平鉴别诊断CHB与LC的曲线下面积(area under the curve,AUC)是0.881(95%CI:0.830~0.932),鉴别诊断CHB/LC与HCC的AUC是0.861(95%CI:0.815~0.908)。3组患者的血清preS1水平与HBsAg(rs=0.799,P<0.001)呈强正相关和Log HBV DNA(rs=0.262,P<0.001)呈弱正相关。此外LC组和HCC组血清preS1水平与肝脏炎症活动分级(rs=0.201,P=0.009)及肝纤维化分期也呈弱正相关性(rs=0.295,P<0.001)。结论血清preS1水平与血清HBsAg、HBV DNA水平和肝脏炎症和纤维化进展呈正相关,有可能成为鉴别诊断HBV相关慢性肝病肝硬化或癌变的候选标志物。

Epstein-Barr病毒感染及相关皮肤疾病

EB病毒是一种人类疱疹病毒,其原发感染多无临床症状或导致传染性单核细胞增多症。原发感染后,EB病毒终身潜伏于健康人体的B淋巴细胞。但是,部分感染者发展为慢性活动性EB病毒感染,或者出现一些EB病毒相关的恶性疾病,如Burkitt's淋巴瘤、鼻咽癌、霍奇金淋巴瘤、牛痘样水疱病样淋巴细胞增生性疾病、NK/T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘤、血管免疫母细胞T细胞淋巴瘤。本文将详述EB病毒感染的特点、机制,并讨论EB病毒相关皮肤疾病的临床、病理特征。

EB病毒感染与消化系统疾病相关性的研究进展

EB病毒(EBV)是淋巴细胞潜隐病毒家族的双链DNA病毒,具有传染性,传播途径主要包括接吻、分享食物或咳嗽等,其主要临床表现为发热、颈部和腋窝等部位淋巴结肿大以及扁桃体肿大等。EBV原发性感染通常无症状且可自愈,其严重程度与宿主免疫系统相关,在炎性肠病、慢性活动性EBV感染性肠炎等消化系统疾病的发生发展中发挥关键性作用。因此,深入研究EBV与消化系统疾病的相关性,可以为相关疾病的治疗提供新思路。

基于Watson关怀理论的个性化护理在慢性乙型肝炎患者中的应用效果

目的 探讨基于Watson关怀理论的个性化护理在慢性乙型肝炎患者中的应用效果,以期为临床护理决策的制定提供参考。方法 选取河南省商丘市立医院2020年3月—2022年3月收治的96例慢性乙型肝炎患者作为研究对象,按照随机数字表分为观察组和对照组,每组48例。观察组患者实施基于Watson关怀理论的个性化护理干预,对照组实施常规护理干预。比较2组患者干预后的治疗依从性,以及干预前后的生活质量及焦虑、抑郁情况。结果 观察组患者治疗依从性为93.75%,高于对照组的77.09%,且差异具有统计学意义(P<0.05)。干预前,2组患者世界卫生组织生存质量测定量表各维度得分比较,差异均无统计学意义(P>0.05);干预后,2组患者世界卫生组织生存质量测定量表各维度得分均高于干预前,且观察组高于同期对照组,差异均有统计学意义(P<0.05)。干预前,2组患者抑郁自评量表(SDS)和焦虑自评量表(SAS)评分比较,差异均无统计学意义(P>0.05);干预后,2组患者SAS、SDS评分均低于干预前,且观察组低于同期对照组,差异均有统计学意义(P<0.05)。结论 基于Watson关怀理论的个性化护理能显著提高患者治疗依从性,改善焦虑、抑郁等不良情绪,提高患者生活质量,值得临床推广使用。

慢性活动性EB病毒感染的研究进展

慢性活动性EB病毒感染(Chronic active EBV infection,CAEBV)是一种少见的发生在无明确免疫缺陷个体的综合征,临床表现多种多样,其病理改变几乎可涉及到各个器官。主要表现为EBV感染后出现慢性或复发性传单样症状,伴随EBV抗体的异常改变或病毒载量的升高,病程中可出现严重的或致死的并发症。文章就其发病机制、临床表现、实验室检查及诊治方案进展作一介绍,以提高临床对慢性活动性EBV的诊治水平。

EB病毒感染患儿淋巴细胞亚群特征和EBV DNA载量分析

目的探讨儿童EB病毒(EBV)感染引起的外周血淋巴细胞亚群的变化特点,并检测EBV感染患儿血清EBV DNA的载量。方法选取17例传染性单核细胞增多症(IM)患儿(IM组)、18例慢性活动性EB病毒(CAEBV)感染患儿(CAEBV组)和15名健康儿童(健康对照组)。采用流式细胞术检测淋巴细胞亚群,荧光定量聚合酶链反应(PCR)检测血清EBV DNA载量,采用Kruskal-Wallis H和Mann-Whitney U检验进行统计分析,Spearman法进行相关分析。结果 IM组淋巴细胞比例和计数、CD4^+T细胞计数、CD8^+T细胞计数均明显高于健康对照组(P<0.05),其中CD8^+T细胞比例和计数的中位数分别高达61.5%和5 217个/μL,自然杀伤(NK)细胞、CD19^+细胞比例明显低于健康对照组(P<0.05)。CAEBV组淋巴细胞比例明显高于对照组(P<0.05),B、NK、CD4^+T、CD8^+T 4种细胞计数2个组之间差异无统计学意义(P>0.05),CD4^+T细胞、CD8^+T细胞计数明显低于IM组(P<0.05)。IM组和CAEBV组EBV DNA载量中位数分别为3.60×103和1.25×104拷贝/m L,2个组之间差异有统计学意义(P=0.027)。IM组和CAEBV组EBV DNA载量与淋巴细胞亚群数量无相关性(P>0.05)。结论 IM患儿与CAEBV感染患儿的淋巴细胞亚群特点有很大不同,IM患儿CD8^+T细胞大量增殖是淋巴细胞计数显著升高的主要原因。综合血清EBV DNA载量与淋巴细胞亚群检测有助于IM与CAEBV感染的鉴别诊断。

活血化瘀法为主治疗慢性丙型肝炎的临床研究

临床比较观察活血化瘀为主的中药组(15例)与干扰素组(15例)治疗慢性丙型病毒性肝炎的疗效。结果发现中药组与干扰素组对HCVRNA的转阴率均为20.00%,抗HCV的转阴率分别为33.33%和26.66%;在症状、肝功能的改善方面,中药组明显优于干扰素组,干扰素组存在不同程度的不良反应。中药组抗病毒远期疗效与干扰素组比较更为稳定持久,具有统计学意义。病理检测结果证实中药组有改善肝细胞充血水肿、汇管区的炎症细胞浸润和肝细胞坏死的作用。

慢性活动性EB病毒感染的诊断标准和治疗

慢性活动EB病毒(CAEBV)感染是一种少见的发生在有免疫能力个体的严重综合征,主要表现为EBV感染后出现慢性或复发性传单样症状伴随EBV抗体的异体改变,病程中可出现严重的或致死的并发症。目前国内尚无CAEBV的诊断标准。参照国外最新研究进展,本文就其发病机制、诊治方案做一介绍,以提高临床对CAEBV的诊治水平。

成人慢性活动性EB病毒感染2例报道并文献复习

目的对成人慢性活动性EB病毒(CAEBV)感染报道和文献复习,提高对成人CAEBV的认识。方法对2例确诊为CAEBV感染患者的临床表现、实验室检查结果、治疗反应及病程发展,结合文献复习分析CAEBV的特征。结果2例患者临床表现和实验室检查符合CAEBV感染的临床特征,1例门诊随访EBV-DNA阳性,1例失访。结论成人CAEBV感染的临床表现多样化,病情进展快,治疗反应不佳,必要时需结合病理活检,以期早期诊断CAEBV,采取积极治疗措施。

重视儿童非肿瘤性EB病毒感染疾病的研究

Epstain-Barr病毒(Epstain-Barr virus,EBV)是一种重要的肿瘤相关病毒,成人感染率超过90%。EB病毒与鼻咽癌、霍奇金和非霍奇金淋巴瘤、胃癌、移植后淋巴增生症等多种肿瘤的发生密切相关。本文介绍了EB病毒感染的实验室诊断方法及其临床应用,重点介绍了儿童常见非肿瘤性EB病毒感染疾病(传染性单核细胞增多症、慢性活动性EB病毒感染、EB病毒相关噬血淋巴组织细胞增生症)的临床特征、诊断指南及需要进一步研究的问题。