巨细胞病毒性肝炎研究进展

曾庆贺; 孟艳; 李玉香

doi:10.3969/j.issn.1001-5256.2023.06.028

巨细胞病毒性肝炎研究进展

DOI: 10.3969/j.issn.1001-5256.2023.06.028

曾庆贺¹,
孟艳²,
李玉香^3, , ,

1.
枣庄市妇幼保健院感染科，山东枣庄 277100
2.
枣庄职业学院医学院，山东枣庄 277800
3.
吉林大学第一医院感染症科，长春 130021

基金项目:

山东省医药卫生科技发展计划项目 (2015WS0012)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：曾庆贺负责文章撰写；孟艳协助文章修改；李玉香负责指导文章及最终定稿。

详细信息

通信作者:
李玉香, yuxiangli612@126.com (ORCID: 0000-0002-4191-2271)

计量
- 文章访问数: 748
- HTML全文浏览量: 73
- PDF下载量: 105
- 被引次数: 0
出版历程
- 收稿日期: 2022-09-23
- 录用日期: 2022-11-04
- 出版日期: 2023-06-20

Research advances in cytomegalovirus hepatitis

Qinghe ZENG¹,
Yan MENG²,
Yuxiang LI^{3
, ,
,}

1.
Department of Infectious Diseases, Zaozhuang Maternal and Child Health Hospital, Zaozhuang, Shandong 277100, China
2.
School of Medicine, Zaozhuang Vocational College, Zaozhuang, Shandong 277800, China
3.
Department of Infectious Diseases, The First Hospital of Jilin University, Changchun 130021, China

Research funding:

Projects of Medical and Health Technology Development Program in Shandong Province (2015WS0012)

More Information

Corresponding author: LI Yuxiang, yuxiangli612@126.com (ORCID: 0000-0002-4191-2271)

摘要

摘要: 巨细胞病毒性肝炎是由人巨细胞病毒感染引起的，儿童和免疫功能低下肝病人群中最常见的一种肝脏疾病。该病无特异性表现，临床上易与其他病毒性肝炎混淆，导致失治误治。巨细胞病毒性肝炎的早期诊断至关重要，以便给予及时有效治疗，合理选择抗病毒药物及疗程。本文对巨细胞病毒性肝炎的病原学、流行病学、发病机制及临床表现、诊断治疗及预防的近年研究进展作一综述。
- 巨细胞病毒感染 /
- 肝炎, 病毒性, 人 /
- 流行病学 /
- 病理状态, 体征和症状 /
- 诊断 /
- 治疗学
Abstract: Cytomegalovirus hepatitis is a liver disease caused by human cytomegalovirus infection and is one of the most common liver diseases in children and immunocompromised individuals. This disease has no specific clinical manifestations and is easily confused with other types of viral hepatitis, which may lead to delayed treatment or mistreatment. Therefore, the early diagnosis of cytomegalovirus hepatitis is of vital importance, and patients should be given timely and effective treatment with appropriately selected antiviral drugs and course of treatment. This article reviews the recent research advances in the etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of cytomegalovirus hepatitis.
- Cytomegalovirus Infections /
- Hepatitis, Viral, Human /
- Epidemiology /
- Pathological Conditions, Signs and Symptoms /
- Diagnosis /
- Therapeutics

HTML全文

图 1 CMV感染后肝脏炎症产生机制

注：PDGFRA，血小板衍生生长因子受体；NRP-2，神经纤毛蛋白-2。

Figure 1. Mechanism of liver inflammation after cytomegalovirus infection

下载: 全尺寸图片幻灯片

参考文献(51)

[1]	ZENG QH, DONG JX, MENG Y, et al. Research progress of clinical epidemiology of human cytomegalovirus[J]. Shandong Med J, 2017, 57(12): 110-116. DOI: 10.3969/j.issn.1002-266X.2017.12.038. 曾庆贺, 董加秀, 孟艳, 等. 人巨细胞病毒感染的流行病学研究进展[J]. 山东医药, 2017, 57(12): 110-116. DOI: 10.3969/j.issn.1002-266X.2017.12.038.
[2]	Infectious Disease Group, Pediatric Branch of Chinese Medical Association. Recommendations for the diagnosis and prevention of cytomegaloviral disease in children[J]. Chin J Pediatr, 2012, 50(4): 290-292. DOI: 10.3760/cma.j.issn.0578-1310.2012.04.013. 中华医学会儿科学分会感染学组, 全国儿科临床病毒感染协作组, 《中华儿科杂志》编辑委员会. 儿童巨细胞病毒性疾病诊断和防治的建议[J]. 中华儿科杂志, 2012, 50(4): 290-292. DOI: 10.3760/cma.j.issn.0578-1310.2012.04.013.
[3]	The Chinese Medical Association of Organ Transplantation. Organ transplant recipients for standardized diagnosis and treatment of cytomegalovirus infection(2019 edition) [J]. Ogran Transplant, 2019, 10(2): 142-148. DOI: 10.3969/j.issn.1674-7445.2019.02.005. 中华医学会器官移植学分会. 器官移植受者巨细胞病毒感染临床诊疗规范(2019版)[J]. 器官移植, 2019, 10(2): 142-148. DOI: 10.3969/j.issn.1674-7445.2019.02.005.
[4]	PANEZ-GALLARDO JK, ATAMARI-ANAHUI N, LIMACHE-ONTIVEROS Y, et al. Cytomegalovirus hepatitis in a 2-month-old infant: a case report[J]. Rev Gastroenterol Peru, 2021, 41(2): 121-125.
[5]	GUPTA P, SURYADEVARA M, DAS A. Cytomegalovirus-induced hepatitis in an immunocompetent patient[J]. Am J Case Rep, 2014, 15: 447-449. DOI: 10.12659/AJCR.890945.
[6]	LAMB SG, STERN H. Cytomegalovirus mononucleosis with jaundice as presenting sign[J]. Lancet, 1966, 2(7471): 1003-1006. DOI: 10.1016/s0140-6736(66)92929-1.
[7]	YONG MK, SHIGLE TL, KIM YJ, et al. American Society for Transplantation and Cellular Therapy Series: #4 - Cytomegalovirus treatment and management of resistant or refractory infections after hematopoietic cell transplantation[J]. Transplant Cell Ther, 2021, 27(12): 957-967. DOI: 10.1016/j.jtct.2021.09.010.
[8]	BOUCOIRAN I, YUDIN M, POLIQUIN V, et al. Corrigendum dans la 《Directive clinique no 420 : Infection à cytomégalovirus pendant la grossesse》[J Obstet Gynaecol Can 43 (2021) 909-925][J]. J Obstet Gynaecol Can, 2021, 43(12): 1467. DOI: 10.1016/j.jogc.2021.10.006.
[9]	RAZONABLE RR, HUMAR A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice[J]. Clin Transplant, 2019, 33(9): e13512. DOI: 10.1111/ctr.13512.
[10]	WONG YJ, CHOO KJL, SOH JXJ, et al. Cytomegalovirus (CMV) hepatitis: an uncommon complication of CMV reactivation in drug reaction with eosinophilia and systemic symptoms[J]. Singapore Med J, 2018, 59(1): 112-113. DOI: 10.11622/smedj.2018016.
[11]	ZHANG C, LIU Y. Study on the diagnosis and treatment of neonatal cytomegalovirus infection[J]. Med Inf, 2021, 34(17): 58-60, 66. DOI: 10.3969/j.issn.1006-1959.2021.17.015. 张称, 刘洋. 新生儿巨细胞病毒感染的诊断、治疗研究[J]. 医学信息, 2021, 34(17): 58-60, 66. DOI: 10.3969/j.issn.1006-1959.2021.17.015.
[12]	HAO HY. Dissecting the regulatory mechanisms of human cytomegalovirus replication and nucleic acid metabolism[D]. University of Chinese Academy of Sciences (Institute Pasteur of Shanghai), 2020. 郝红云. 探究人巨细胞病毒复制及核酸代谢调控机制[D]. 中国科学院大学(中国科学院上海巴斯德研究所), 2020.
[13]	BUNCHORNTAVAKUL C, REDDY KR. Epstein-Barr virus and cytomegalovirus infections of the liver[J]. Gastroenterol Clin North Am, 2020, 49(2): 331-346. DOI: 10.1016/j.gtc.2020.01.008.
[14]	LANDOLFO S, GARIGLIO M, GRIBAUDO G, et al. The human cytomegalovirus[J]. Pharmacol Ther, 2003, 98(3): 269-297. DOI: 10.1016/s0163-7258(03)00034-2.
[15]	WANG S. Research progress of the biological function of proteins in human cytomegalovirus mainly encodes[J]. Int J Pediat, 2020, 47(2): 100-105. DOI: 10.3760/cma.j.issn.1673-4408.2020.02.007. 王爽. 人巨细胞病毒主要编码蛋白生物学功能的研究进展[J]. 国际儿科学杂志, 2020, 47(2): 100-105. DOI: 10.3760/cma.j.issn.1673-4408.2020.02.007.
[16]	GRIFFITHS P, BARANIAK I, REEVES M. The pathogenesis of human cytomegalovirus[J]. J Pathol, 2015, 235(2): 288-297. DOI: 10.1002/path.4437.
[17]	TOMTISHEN JP 3^rd. Human cytomegalovirus tegument proteins (pp65, pp71, pp150, pp28) [J]. Virol J, 2012, 9: 22. DOI: 10.1186/1743-422X-9-22.
[18]	GUO S, YU MM, LI G, et al. Epitoprotein H genotype of infantile human cytomegalovirus clinical isolate[J]. Chin J Pediat, 2013, 51(4): 260-264. DOI: 10.3760/cma.j.issn.0578-1310.2013.04.005. 郭珊, 于锰锰, 李革, 等. 婴幼儿人巨细胞病毒临床分离株包膜糖蛋白H基因型别研究[J]. 中华儿科杂志, 2013, 51(4): 260-264. DOI: 10.3760/cma.j.issn.0578-1310.2013.04.005.
[19]	GUO G, ZHANG L, YE S, et al. Polymorphisms and features of cytomegalovirus UL144 and UL146 in congenitally infected neonates with hepatic involvement[J]. PLoS One, 2017, 12(2): e0171959. DOI: 10.1371/journal.pone.0171959.
[20]	PETRUCELLI A, UMASHANKAR M, ZAGALLO P, et al. Interactions between proteins encoded within the human cytomegalovirus UL133-UL138 locus[J]. J Virol, 2012, 86(16): 8653-8662. DOI: 10.1128/JVI.00465-12.
[21]	ALIBEGOVIC E, KURTCEHAJIC A, ILIC B, et al. Cytomegalovirus cholangiopathy in an immunocompetent patient: a case report and literature review[J]. Case Reports Hepatol, 2021, 2021: 2420668. DOI: 10.1155/2021/2420668.
[22]	FAKHREDDINE AY, FRENETTE CT, KONIJETI GG. A practical review of cytomegalovirus in gastroenterology and hepatology[J]. Gastroenterol Res Pract, 2019, 2019: 6156581. DOI: 10.1155/2019/6156581.
[23]	LIU RH, LIU HL, WANG B, et al. Treatment of various clinical types of infant HCMV hepatitis[J]. Chin J Hepatol, 2006, 14(3): 235, 240. DOI: 10.3760/j.issn:1007-3418.2006.03.026. 刘瑞海, 刘华林, 王斌, 等. 婴儿巨细胞病毒性肝炎临床分型治疗研究[J]. 中华肝脏病杂志, 2006, 14(3): 235, 240. DOI: 10.3760/j.issn:1007-3418.2006.03.026.
[24]	ZENG QH, XIAO LY, MENG Y, et al. Epidemiological survey of human cytomegalovirus infection in children aged 0-12 years in Zaozhuang [J]. Chin J Woman Child Health Res, 2020, 31(9): 1180-1184. DOI: 10.3969/j.issn.1673-5293.2020.09.012. 曾庆贺, 肖立燕, 孟艳, 等. 枣庄地区0~12岁儿童人巨细胞病毒感染的流行病学调查[J]. 中国妇幼健康研究, 2020, 31(9): 1180-1184. DOI: 10.3969/j.issn.1673-5293.2020.09.012.
[25]	ADLAND E, KLENERMAN P, GOULDER P, et al. Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era[J]. Front Microbiol, 2015, 6: 1016. DOI: 10.3389/fmicb.2015.01016.
[26]	SHE WM. Cytomegalovirus hepatitis in an adult with normal immune function: case report[J]. Chin J Clin Med, 2018, 25(4): 679-681. DOI: 10.12025/j.issn.1008-6358.2018.20170980. 佘为民. 免疫功能正常成人巨细胞病毒性肝炎1例报告[J]. 中国临床医学, 2018, 25(4): 679-681. DOI: 10.12025/j.issn.1008-6358.2018.20170980.
[27]	DA CUNHA T, WU GY. Cytomegalovirus hepatitis in immunocompetent and immunocompromised hosts[J]. J Clin Transl Hepatol, 2021, 9(1): 106-115. DOI: 10.14218/JCTH.2020.00088.
[28]	SEEHOFER D, RAYES N, TULLIUS SG, et al. CMV hepatitis after liver transplantation: incidence, clinical course, and long-term follow-up[J]. Liver Transpl, 2002, 8(12): 1138-1146. DOI: 10.1053/jlts.2002.36732.
[29]	HASSAN-WALKER AF, MATTES FM, GRIFFITHS PD, et al. Quantity of cytomegalovirus DNA in different leukocyte populations during active infection in vivo and the presence of gB and UL18 transcripts[J]. J Med Virol, 2001, 64(3): 283-289. DOI: 10.1002/jmv.1048.
[30]	WU K, OBERSTEIN A, WANG W, et al. Role of PDGF receptor-α during human cytomegalovirus entry into fibroblasts[J]. Proc Natl Acad Sci U S A, 2018, 115(42): E9889-E9898. DOI: 10.1073/pnas.1806305115.
[31]	GRIFFITHS P, REEVES M. Pathogenesis of human cytomegalovirus in the immunocompromised host[J]. Nat Rev Microbiol, 2021, 19(12): 759-773. DOI: 10.1038/s41579-021-00582-z.
[32]	ZHANG WN, DING CG, ZHAO HY, et al. Changes of serum IFN-γ and IL-18 levels in children with cytomegalovirus hepatitis[J]. J Prac Hepatol, 2021, 24(2): 208-211. DOI: 10.3969/j.issn.1672-5069.2021.02.015. 张维娜, 丁传刚, 赵红英, 等. 巨细胞病毒性肝炎患儿血清IFN-γ和IL-18水平变化及其与预后的关系探讨[J]. 实用肝脏病杂志, 2021, 24(2): 208-211. DOI: 10.3969/j.issn.1672-5069.2021.02.015.
[33]	MALONE D, LUNEMANN S, HENGST J, et al. Cytomegalovirus-driven adaptive-like natural killer cell expansions are unaffected by concurrent chronic hepatitis virus infections[J]. Front Immunol, 2017, 8: 525. DOI: 10.3389/fimmu.2017.00525.
[34]	BERNSON E, HALLNER A, SANDER FE, et al. Cytomegalovirus serostatus affects autoreactive NK cells and outcomes of IL2-based immunotherapy in acute myeloid leukemia[J]. Cancer Immunol Res, 2018, 6(9): 1110-1119. DOI: 10.1158/2326-6066.CIR-17-0711.
[35]	WEI AP, SONG YQ, PENG W, et al. Research progress in immunological mechanism of human cytomegalovirus infection[J]. Med Recapitulate, 2022, 28(7): 1308-1315. DOI: 10.3969/j.issn.1006-2084.2022.07.011. 韦爱萍, 宋雅琴, 彭薇, 等. 人巨细胞病毒感染机体细胞免疫学机制的研究进展[J]. 医学综述, 2022, 28(7): 1308-1315. DOI: 10.3969/j.issn.1006-2084.2022.07.011.
[36]	STOJANOVIC B, MILOVANOVIC J, ARSENIJEVIC A, et al. Galectin-3 deficiency facilitates TNF-α-dependent hepatocyte death and liver Inflammation in MCMV infection[J]. Front Microbiol, 2019, 10: 185. DOI: 10.3389/fmicb.2019.00185.
[37]	BELLON M, NICOT C. Telomere dynamics in immune senescence and exhaustion triggered by chronic viral infection[J]. Viruses, 2017, 9(10): 289. DOI: 10.3390/v9100289.
[38]	SUO M, EKLADIOUS A, SAHEBOLAMRI M, et al. Acute CMV hepatitis in an immunocompetent patient[J]. BMJ Case Rep, 2020, 13(12): e234811. DOI: 10.1136/bcr-2020-234811.
[39]	McDONALD GB, SARMIENTO JI, REES-LUI G, et al. Cytomegalovirus hepatitis after bone marrow transplantation: An autopsy study with clinical, histologic and laboratory correlates[J]. J Viral Hepat, 2019, 26(11): 1344-1350. DOI: 10.1111/jvh.13176.
[40]	NOOR A, PANWALA A, FOROUHAR F, et al. Hepatitis caused by herpes viruses: A review[J]. J Dig Dis, 2018, 19(8): 446-455. DOI: 10.1111/1751-2980.12640.
[41]	TANG YT, GUAN XQ, ZHAO RQ. Clinical pathological features of cytomegalovirus hepatitis in infants [J]. Chin J Hepatol, 2009, 17(1): 21-23. DOI: 10.3760/cma.j.issn.1007-3418.2009.01.007. 唐袁婷, 管小琴, 赵瑞秋. 婴儿巨细胞病毒性肝炎临床病理分析[J]. 中华肝脏病杂志, 2009, 17(1): 21-23. DOI: 10.3760/cma.j.issn.1007-3418.2009.01.007.
[42]	FANG F. Cytomegalovirus infection in liver function damage[J]. J Appl Clin Pediatr, 2006, 21(10): 582-583. DOI: 10.3969/j.issn.1003-515X.2006.10.004. 方峰. 巨细胞病毒感染与肝脏损害[J]. 实用儿科临床杂志, 2006, 21(10): 582-583. DOI: 10.3969/j.issn.1003-515X.2006.10.004.
[43]	MU J, YANG Y, HE Q. Clinical features and treatment outcome of cytomegalovirus hepatitis in infants[J]. Beijing Med J, 2019, 41(1): 42-45. DOI: 10.15932/j.0253-9713.2019.01.012. 穆静, 杨燕, 何强. 婴儿巨细胞病毒肝炎临床特征及治疗转归分析[J]. 北京医学, 2019, 41(1): 42-45. DOI: 10.15932/j.0253-9713.2019.01.012.
[44]	MIN CY, SONG JY, JEONG SJ. Characteristics and prognosis of hepatic cytomegalovirus infection in children: 10 years of experience at a university hospital in Korea[J]. Korean J Pediatr, 2017, 60(8): 261-265. DOI: 10.3345/kjp.2017.60.8.261.
[45]	ZANG H, ZHU B, YOU SL, et al. Analysis on clinical manifestations and pathological features of CMV hepatitis in adult patients[J]. Pract Prevent Med, 2012, 19(11): 1684-1686. DOI: 10.3969/j.issn.1006-3110.2012.11.030. 臧红, 朱冰, 游绍莉, 等. 成人巨细胞病毒性肝炎临床表现及病理特点分析[J]. 实用预防医学, 2012, 19(11): 1684-1686. DOI: 10.3969/j.issn.1006-3110.2012.11.030.
[46]	HUANG JW, HAN FZ. Research advances in Epstein-Barr viral hepatitis [J]. J Clin Hepatol, 2018, 34(6): 1333-1337. DOI: 10.3969/j.issn.1001-5256.2018.06.043. 黄姜伟, 韩方正. EB病毒性肝炎的研究进展[J]. 临床肝胆病杂志, 2018, 34(6): 1333-1337. DOI: 10.3969/j.issn.1001-5256.2018.06.043.
[47]	HAI J, LUO HS. Advance research on liver-related diseases caused by cytomegalovirus[J]. Chin J Gastroenterol Hepatol, 2020, 29(2): 224-228. DOI: 10.3969/j.issn.1006-5709.2020.02.021. 海静, 罗和生. 巨细胞病毒导致的肝脏相关疾病的研究进展[J]. 胃肠病学和肝病学杂志, 2020, 29(2): 224-228. DOI: 10.3969/j.issn.1006-5709.2020.02.021.
[48]	KIMBERLIN DW, JESTER PM, SÁNCHEZ PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease[J]. N Engl J Med, 2015, 372(10): 933-943. DOI: 10.1056/NEJMoa1404599.
[49]	BONATTI H, SIFRI CD, LARCHER C, et al. Use of cidofovir for cytomegalovirus disease refractory to ganciclovir in solid organ recipients[J]. Surg Infect (Larchmt), 2017, 18(2): 128-136. DOI: 10.1089/sur.2015.266.
[50]	KIM ES. Letermovir: first global approval[J]. Drugs, 2018, 78(1): 147-152. DOI: 10.1007/s40265-017-0860-8.
[51]	FULKERSON HL, NOGALSKI MT, COLLINS-MCMILLEN D, et al. Overview of human cytomegalovirus pathogenesis[J]. Methods Mol Biol, 2021, 2244: 1-18. DOI: 10.1007/978-1-0716-1111-1_1.