慢性活动性EB病毒病肝损伤的研究进展

方姝; 王晶石; 王昭

doi:10.12449/JCH260901

慢性活动性EB病毒病肝损伤的研究进展

DOI: 10.12449/JCH260901

首都医科大学附属北京友谊医院血液内科，北京 100050

基金项目:

国家自然科学基金 (82370185);

北京市临床重点专科项目 (2024);

北京市西城区科技专项 (XCSTS-TI2024-38);

北京市自然科学基金 (7262031);

首都卫生发展科研专项 (2026-2-1032)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：方姝参与论文设计及起草；王晶石参与论文设计、修改；王昭参与论文选题、设计及修改。

详细信息

通信作者:
王昭， wangzhao@ccmu.edu.cn （ORCID： 0000-0003-1067-4589）

计量
- 文章访问数: 11
- HTML全文浏览量: 5
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2026-08-17
- 录用日期: 2026-09-15
- 出版日期: 2026-09-25

Research advances in liver injury associated with chronic active Epstein-Barr virus disease

Department of Hematology，Beijing Friendship Hospital，Capital Medical University，Beijing 100050，China

Research funding:

National Natural Science Foundation of China (82370185);

Beijing Clinical Key Specialty Project (2024);

Beijing Xicheng District Science and Technology Special Project (XCSTS-TI2024-38);

Beijing Natural Science Foundation (7262031);

Capital’s Funds for Health Improvement and Research (2026-2-1032)

More Information

Corresponding author: Wang Zhao， wangzhao@ccmu.edu.cn （ORCID： 0000-0003-1067-4589）

摘要

摘要: 慢性活动性EB病毒病（CAEBVD）是一种由EB病毒感染T细胞、自然杀伤细胞所致的淋巴增殖性疾病。肝脏是CAEBVD最常累及的靶器官之一，47%～67.1%的患者可出现不同程度的肝损伤。本文从发病机制、临床表现、病理特征、诊断标准、治疗及预后等方面，对CAEBVD肝损伤的特点进行系统梳理，以期提高临床医师对该病的认识，实现早期诊断和及时治疗。
- 疱疹病毒4型，人 /
- 肝损伤 /
- 病理过程 /
- 诊断 /
- 治疗学
Abstract: Chronic active Epstein-Barr virus disease （CAEBVD） is a lymphoproliferative disorder caused by Epstein-Barr virus infection of T cells and natural killer cells. The liver is one of the most commonly affected organs in CAEBVD， with 47% to 67.1% of patients exhibiting varying degrees of liver injury. This article systematically reviews the characteristics of liver injury associated with CAEBVD from the aspects of its pathogenesis， clinical manifestations， pathological features， diagnostic criteria， treatment， and prognosis， in order to improve awareness of this disease among clinicians and promote early diagnosis and timely treatment.
- Herpesvirus 4， Human /
- Liver Injury /
- Pathologic Processes /
- Diagnosis /
- Therapeutics

HTML全文

参考文献(46)

[1]	Cohen J I. Epstein-Barr virus infection[J]. N Engl J Med, 2000, 343( 7): 481- 492. DOI: 10.1056/NEJM200008173430707.
[2]	Kawa K, Okamura T, Yagi K, et al. Mosquito allergy and Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease[J]. Blood, 2001, 98( 10): 3173- 3174. DOI: 10.1182/blood.v98.10.3173.
[3]	Quintanilla-Martinez L, Swerdlow S H, Tousseyn T, et al. New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders[J]. Virchows Arch, 2023, 482( 1): 227- 244. DOI: 10.1007/s00428-022-03414-4.
[4]	Kimura H. EBV in T-/ NK-cell tumorigenesis[J]. Adv Exp Med Biol, 2018, 1045: 459- 475. DOI: 10.1007/978-981-10-7230-7_21.
[5]	Cohen J I, Jaffe E S, Dale J K, et al. Characterization and treatment of chronic active Epstein-Barr virus disease: A 28-year experience in the United States[J]. Blood, 2011, 117( 22): 5835- 5849. DOI: 10.1182/blood-2010-11-316745.
[6]	Méndez-Sánchez N, Aguilar-Domínguez C, Chávez-Tapia N C, et al. Hepatic manifestations of Epstein-Barr viral infection[J]. Ann Hepatol, 2005, 4( 3): 205- 209.
[7]	Lin J, Su M F, Zheng J L, et al. Fas/FasL and complement activation are associated with chronic active epstein-barr virus hepatitis[J]. J Clin Transl Hepatol, 2023, 11( 3): 540- 549. DOI: 10.14218/JCTH.2022.00227.
[8]	Drebber U, Kasper H U, Krupacz J, et al. The role of Epstein-Barr virus in acute and chronic hepatitis[J]. J Hepatol, 2006, 44( 5): 879- 885. DOI: 10.1016/j.jhep.2006.02.006.
[9]	Li X J, Qu L J, Zheng X W, et al. Clinicopathologic features of chronic active Epstein-Barr virus hepatitis[J]. World Chin J Dig, 2013, 21( 23): 2325. DOI: 10.11569/wcjd.v21.i23.2325.
[10]	Wang J S, Su M, Wei N, et al. Chronic active Epstein-Barr virus disease originates from infected hematopoietic stem cells[J]. Blood, 2024, 143( 1): 32- 41. DOI: 10.1182/blood.2023021074.
[11]	Hong M, Ko Y H, Yoo K H, et al. EBV-positive T/NK-cell lymphoproliferative disease of childhood[J]. Korean J Pathol, 2013, 47( 2): 137- 147. DOI: 10.4132/KoreanJPathol.2013.47.2.137.
[12]	Toner K, Bollard C M. EBV+ lymphoproliferative diseases: Opportunities for leveraging EBV as a therapeutic target[J]. Blood, 2022, 139( 7): 983- 994. DOI: 10.1182/blood.2020005466.
[13]	Collins P J, Fox C P, George L, et al. Characterizing EBV-associated lymphoproliferative diseases and the role of myeloid-derived suppressor cells[J]. Blood, 2021, 137( 2): 203- 215. DOI: 10.1182/blood.2020005611.
[14]	Kawada J I, Ito Y, Ohshima K, et al. Updated guidelines for chronic active Epstein–Barr virus disease[J]. Int J Hematol, 2023, 118( 5): 568- 576. DOI: 10.1007/s12185-023-03660-5.
[15]	Okuno Y, Murata T, Sato Y, et al. Defective Epstein-Barr virus in chronic active infection and haematological malignancy[J]. Nat Microbiol, 2019, 4( 3): 404- 413. DOI: 10.1038/s41564-018-0334-0.
[16]	Jiang L, Gu Z H, Yan Z X, et al. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma[J]. Nat Genet, 2015, 47( 9): 1061- 1066. DOI: 10.1038/ng.3358.
[17]	Murata T, Okuno Y, Sato Y, et al. Oncogenesis of CAEBV revealed: Intragenic deletions in the viral genome and leaky expression of lytic genes[J]. Rev Med Virol, 2020, 30( 2): e2095. DOI: 10.1002/rmv.2095.
[18]	Ohga S, Nomura A, Takada H, et al. Epstein-Barr virus(EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection[J]. J Infect Dis, 2001, 183( 1): 1- 7. DOI: 10.1086/317653.
[19]	Henter J I, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis[J]. Pediatr Blood Cancer, 2007, 48( 2): 124- 131. DOI: 10.1002/pbc.21039.
[20]	Park J H, Noh J C, Park H M, et al. A case of Epstein-Barr virus infection with gall bladder and common bile duct stones in an otherwise healthy child[J]. Pediatr Gastroenterol Hepatol Nutr, 2012, 15( 1): 57. DOI: 10.5223/kjpgn.2012.15.1.57.
[21]	Lawee D. Mild infectious mononucleosis presenting with transient mixed liver disease: Case report with a literature review[J]. Can Fam Physician, 2007, 53( 8): 1314- 1316.
[22]	Markin R S. Manifestations of Epstein-Barr virus-associated disorders in liver[J]. Liver, 1994, 14( 1): 1- 13. DOI: 10.1111/j.1600-0676.1994.tb00001.x.
[23]	Zhou Zhe, Shao Lingyun, Zhang Wenhong. Progress in clinical diagnosis and treatment of chronic active Epstein-Barr virus infection[J]. J Clin Hematol, 2022, 35( 1): 11- 15. 周哲, 邵凌云, 张文宏. 慢性活动性EB病毒感染临床诊断与治疗进展[J]. 临床血液学杂志, 2022, 35( 1): 11- 15.
[24]	Xu Jinghang, Yu Yanyan, Xu Xiaoyuan. Clinical features of Epstein-Barr virus infection associated to liver injury in adolescents and adults[J]. Chin J Hepatol, 2021, 29( 10): 915- 918. DOI: 10.3760/cma.j.cn501113-20210902-00445. 徐京杭, 于岩岩, 徐小元. 青少年和成人EB病毒感染相关肝损伤的临床特征[J]. 中华肝脏病杂志, 2021, 29( 10): 915- 918. DOI: 10.3760/cma.j.cn501113-20210902-00445.
[25]	Mellinger J L, Rossaro L, Naugler W E, et al. Epstein–Barr virus(EBV) related acute liver failure: A case series from the US acute liver failure study group[J]. Dig Dis Sci, 2014, 59( 7): 1630- 1637. DOI: 10.1007/s10620-014-3029-2.
[26]	Suh N, Liapis H, Misdraji J, et al. Epstein-Barr virus hepatitis: Diagnostic value of in situ hybridization, polymerase chain reaction, and immunohistochemistry on liver biopsy from immunocompetent patients[J]. Am J Surg Pathol, 2007, 31( 9): 1403- 1409. DOI: 10.1097/PAS.0b013e31802ffdd5.
[27]	Lymphocyte Group of Hematology Branch of the Chinese Medical Association; Hematology Group of Pediatrics Branch of the Chinese Medical Association; Infectious Disease Branch of the Chinese Medical Association. Expert consensus on diagnosis and treatment of chronic active Epstein-Barr virus disease(2025 edition)[J]. Natl Med J China, 2025, 105( 17): 1322- 1330. DOI: 10.3760/cma.j.cn112137-20241229-02956. 中华医学会血液学分会淋巴细胞学组, 中华医学会儿科学分会血液学组, 中华医学会感染病学分会. 慢性活动性EB病毒病诊治专家共识(2025版)[J]. 中华医学杂志, 2025, 105( 17): 1322- 1330. DOI: 10.3760/cma.j.cn112137-20241229-02956.
[28]	Wang J S, Wang Y N, Wu L, et al. PEG-aspargase and DEP regimen combination therapy for refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis[J]. J Hematol Oncol, 2016, 9( 1): 84. DOI: 10.1186/s13045-016-0317-7.
[29]	Ma H H, Zhang L P, Wei A, et al. Outcome of L-DEP regimen for treatment of pediatric chronic active Epstein–Barr virus infection[J]. Orphanet J Rare Dis, 2021, 16( 1): 269. DOI: 10.1186/s13023-021-01909-y.
[30]	Kawa K, Sawada A, Sato M, et al. Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection[J]. Bone Marrow Transplant, 2011, 46( 1): 77- 83. DOI: 10.1038/bmt.2010.122.
[31]	Yonese I, Sakashita C, Imadome K I, et al. Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification[J]. Blood Adv, 2020, 4( 13): 2918- 2926. DOI: 10.1182/bloodadvances.2020001451.
[32]	Kimura H, Ito Y, Kawabe S, et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: Prospective analysis of 108 cases[J]. Blood, 2012, 119( 3): 673- 686. DOI: 10.1182/blood-2011-10-381921.
[33]	Sawada A, Inoue M, Kawa K. How we treat chronic active Epstein-Barr virus infection[J]. Int J Hematol, 2017, 105( 4): 406- 418. DOI: 10.1007/s12185-017-2192-6.
[34]	Arai A. Advances in the study of chronic active Epstein-Barr virus infection: Clinical features under the 2016 WHO classification and mechanisms of development[J]. Front Pediatr, 2019, 7: 14. DOI: 10.3389/fped.2019.00014.
[35]	Chen R Y, Lin Q, Zhu Y, et al. Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children[J]. Orphanet J Rare Dis, 2023, 18( 1): 297. DOI: 10.1186/s13023-023-02861-9.
[36]	Ma Y X, Zhang P L, Bao Y H, et al. Outcomes of programmed death protein-1 inhibitors treatment of chronic active Epstein Barr virus infection: A single center retrospective analysis[J]. Front Immunol, 2023, 14: 1093719. DOI: 10.3389/fimmu.2023.1093719.
[37]	Song Y, Wang J S, Wang Y N, et al. PD-1 blockade and lenalidomide combination therapy for chronic active Epstein-Barr virus infection[J]. Clin Microbiol Infect, 2023, 29( 6): 796.e7- 796.e13. DOI: 10.1016/j.cmi.2023.01.017.
[38]	Cui X L, Snapper C M. Epstein Barr virus: Development of vaccines and immune cell therapy for EBV-associated diseases[J]. Front Immunol, 2021, 12: 734471. DOI: 10.3389/fimmu.2021.734471.
[39]	Liu Y D, Cai J Y, Wang T Y, et al. Glycoprotein 350-targeted chimeric antigen receptor T-cell therapy for nonneoplastic chronic active Epstein-Barr virus infection: A case report[J]. Transl Pediatr, 2024, 13( 12): 2305- 2310. DOI: 10.21037/tp-24-292.
[40]	Yan S J, Ming X, Zhu X J, et al. Role of rapidly evolving immunotherapy in chronic active Epstein-Barr virus disease[J]. Front Immunol, 2024, 15: 1451977. DOI: 10.3389/fimmu.2024.1451977.
[41]	Yoshimori M, Shibayama H, Imadome K I, et al. Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection[J]. Blood Adv, 2021, 5( 7): 1805- 1815. DOI: 10.1182/bloodadvances.2020002417.
[42]	Shafiee A, Shamsi S, Kohandel Gargari O, et al. EBV associated T- and NK-cell lymphoproliferative diseases: A comprehensive overview of clinical manifestations and novel therapeutic insights[J]. Rev Med Virol, 2022, 32( 4): e2328. DOI: 10.1002/rmv.2328.
[43]	Arai A, Sakashita C, Hirose C, et al. Hematopoietic stem cell transplantation for adults with EBV-positive T- or NK-cell lymphoproliferative disorders: Efficacy and predictive markers[J]. Bone Marrow Transplant, 2016, 51( 6): 879- 882. DOI: 10.1038/bmt.2016.3.
[44]	Kimura H, Morishima T, Kanegane H, et al. Prognostic factors for chronic active Epstein-Barr virus infection[J]. J Infect Dis, 2003, 187( 4): 527- 533. DOI: 10.1086/367988.
[45]	Lin J C, Chen X K, Wu H M, et al. Peripheral blood lymphocyte counts in patients with infectious mononucleosis or chronic active Epstein-Barr virus infection and prognostic risk factors of chronic active Epstein-Barr virus infection[J]. Am J Transl Res, 2021, 13( 11): 12797- 12806.
[46]	Chen S T, Wei A, Ma H H, et al. Clinical features and prognostic factors of children with chronic active Epstein-Barr virus infection: A retrospective analysis of a single center[J]. J Pediatr, 2021, 238: 268- 274. DOI: 10.1016/j.jpeds.2021.07.009.