新型冠状病毒肺炎相关肝损伤研究进展

崔浩; 梁静; 向慧玲

doi:10.3969/j.issn.1001-5256.2022.04.039

新型冠状病毒肺炎相关肝损伤研究进展

DOI: 10.3969/j.issn.1001-5256.2022.04.039

崔浩^{1, 2},
梁静^{1, 2, , ,},
向慧玲²

1.
天津医科大学三中心临床学院，天津 300170
2.
天津市第三中心医院消化肝病科，天津 300170

基金项目:

天津科技重大专项与工程重大疾病防治 (19ZXDBSY00030)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：崔浩负责拟定写作思路，查阅文献，撰写论文；向慧玲提出指导性意见并参与支持性工作；梁静负责修改及指导撰写文章并最后定稿。

详细信息

通信作者:
梁静，haolele77@sina.com

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出版历程
- 收稿日期: 2021-12-01
- 录用日期: 2021-12-31
- 出版日期: 2022-04-20

Research advances in coronavirus disease 2019-related liver injury

Hao CUI^{1, 2},
Jing LIANG^{1, 2
, ,
,},
Huiling XIANG²

1.
The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
2.
Department of Hepatology, Tianjin Third Central Hospital, Tianjin 300170, China

Research funding:

Tianjin Science and Technology Plan Project (19ZXDBSY00030)

More Information

Corresponding author: LIANG Jing, haolele77@sina.com(ORCID: 0000-0001-5114-9030)

摘要

摘要: 新型冠状病毒肺炎的大流行对全球的公共卫生安全造成了巨大威胁及挑战，并改变了医疗配置的优先性。在新型冠状病毒肺炎的临床诊治中，可以观察到相当比例的患者发生肝损伤，尤其是重症或危重症患者。本文总结新型冠状病毒肺炎致肝损伤的流行病学、机制、临床特征及治疗，希望可对临床医生的决策和优化治疗提供帮助。
- 新型冠状病毒肺炎 /
- 肝功能不全 /
- 药物性肝损伤 /
- 治疗学
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has brought great threats and challenges to global public health and has changed the priorities of medical resource allocation. A considerable proportion of patients with liver injury is observed during the clinical diagnosis and treatment of COVID-19, especially in those with a severe or critical illness. This article summarizes the epidemiology, mechanism, clinical features, and treatment of liver injury caused by COVID-19, in order to help clinicians with decision making and treatment optimization.
- Coronavirus Disease 2019 /
- Hepatic Insufficiency /
- Drug Induced Liver Injury /
- Therapeutics

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表 1 各地区COVID-19相关肝损伤患者主要临床特征

Table 1. Main clinical characteristics of patients with COVID-19 related liver injury in various regions

第一作者	时间	地区	样本量(例)	年龄(岁)	男性占比[例(%)]	重症患者占比[例(%)]	有基础肝病占比[例(%)]	肝功能异常项目及占比
Guan^[2]	2020.4	中国(多中心)	1099	47(35~58)	640(58.2)	173(15.7)	23(2.1)	ALT(21.3%)；AST(22.2%)；TBil(10.5%)；LDH(41.0%)
Cai^[3]	2020.9	中国深圳	417	47(34~60)	198(45.3)	85(20.38)	21(5.04)	ALT(12.9%)；AST(18.23%)；TBil(23.19%)；ALP(4.55%)；GGT(16.31%)
Huang^[4]	2020.2	中国武汉	41	49	30(73.0)	13(31.7)	1(2.4)	AST(37%)；LDH(73%)
钱志平^[5]	2020.3	中国上海	324	51(15~88)	167(51.5)	26(8.0)	90(27.8)	ALT(15.7%)；ALP(1.2%)；INR(0.6%)
龙丹^[6]	2020.7	中国湖北	201	7~96	93(46.3)	28(13.9)		ALT/AST(18.4%)；TBil(0.5%)
Richardson^[7]	2020.5	美国(多中心)	5700	63(0~107)	3437(60.3)			ALT(39.0%)；AST(58.4%)
Bloom^[8]	2021.3	美国	60	57	39(65.0)		4(7.0)	ALT/AST/ALP/TBil至少有一项生化异常(69%)
注：LDH，乳酸脱氢酶。

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参考文献(49)

[1]	ZHOU P, YANG XL, WANG XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin[J]. Nature, 2020, 579(7798): 270-273. DOI: 10.1038/s41586-020-2012-7.
[2]	GUAN WJ, NI ZY, HU Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China[J]. N Engl J Med, 2020, 382(18): 1708-1720. DOI: 10.1056/NEJMoa2002032.
[3]	CAI Q, HUANG D, YU H, et al. COVID-19: Abnormal liver function tests[J]. J Hepatol, 2020, 73(3): 566-574. DOI: 10.1016/j.jhep.2020.04.006.
[4]	HUANG C, WANG Y, LI X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020, 395(10223): 497-506. DOI: 10.1016/S0140-6736(20)30183-5.
[5]	QIAN ZP, MEI X, ZHANG YY, et al. Analysis of baseline liver biochemical parameters in 324 cases with novel coronavirus pneumonia in Shanghai area[J]. Chin J Hepatol, 2020, 28 (3): 229-233. DOI: 10.3760/cma.j.cn501113-20200229-00076. 钱志平, 梅雪, 张宇一, 等. 上海地区324例新型冠状病毒肺炎患者基线肝脏生物化学指标分析[J]. 中华肝脏病杂志, 2020, 28(3): 229-233. DOI: 10.3760/cma.j.cn501113-20200229-00076.
[6]	LONG D, QIN LH, GAO S. Clinical features of liver injury in patients with coronavirus disease 2019: An analysis of 201 cases[J]. J Clin Hepatol, 2020, 36(7): 1567-1570. DOI: 10.3969/j.issn.1001-5256.2020.07.023. 龙丹, 秦凌辉, 高山. 201例新型冠状病毒肺炎患者肝损害临床特征分析[J]. 临床肝胆病杂志, 2020, 36(7): 1567-1570. DOI: 10.3969/j.issn.1001-5256.2020.07.023.
[7]	RICHARDSON S, HIRSCH JS, NARASIMHAN M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area[J]. JAMA, 2020, 323(20): 2052-2059. DOI: 10.1001/jama.2020.6775.
[8]	BLOOM PP, MEYEROWITZ EA, REINUS Z, et al. Liver biochemistries in hospitalized patients with COVID-19[J]. Hepatology, 2021, 73(3): 890-900. DOI: 10.1002/hep.31326.
[9]	ONG J, YOUNG BE, ONG S. COVID-19 in gastroenterology: A clinical perspective[J]. Gut, 2020, 69(6): 1144-1145. DOI: 10.1136/gutjnl-2020-321051.
[10]	JOTHIMANI D, VENUGOPAL R, ABEDIN MF, et al. COVID-19 and the liver[J]. J Hepatol, 2020, 73(5): 1231-1240. DOI: 10.1016/j.jhep.2020.06.006.
[11]	MAO R, QIU Y, HE JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2020, 5(7): 667-678. DOI: 10.1016/S2468-1253(20)30126-6.
[12]	HENRY BM, OLIVEIRA MHS, BENOIT S, et al. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis[J]. Clin Chem Lab Med, 2020, 58(7): 1021-1028. DOI: 10.1515/cclm-2020-0369.
[13]	QI X, LIU Y, WANG J, et al. Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis: A multicentre cohort study[J]. Gut, 2021, 70(2): 433-436. DOI: 10.1136/gutjnl-2020-321666.
[14]	HOFFMANN M, KLEINE-WEBER H, SCHROEDER S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor[J]. Cell, 2020, 181(2): 271-280. DOI: 10.1016/j.cell.2020.02.052.
[15]	SONZOGNI A, PREVITALI G, SEGHEZZI M, et al. Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations[J]. Liver Int, 2020, 40(9): 2110-2116. DOI: 10.1111/liv.14601.
[16]	WANG Y, LIU S, LIU H, et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19[J]. J Hepatol, 2020, 73(4): 807-816. DOI: 10.1016/j.jhep.2020.05.002.
[17]	PERLMAN S, NETLAND J. Coronaviruses post-SARS: Update on replication and pathogenesis[J]. Nat Rev Microbiol, 2009, 7(6): 439-450. DOI: 10.1038/nrmicro2147.
[18]	CHU H, CHAN JF, YUEN TT, et al. Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: An observational study[J]. Lancet Microbe, 2020, 1(1): e14-e23. DOI: 10.1016/S2666-5247(20)30004-5.
[19]	YANG L, HAN Y, NILSSON-PAYANT BE, et al. A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids[J]. Cell Stem Cell, 2020, 27(1): 125-136. DOI: 10.1016/j.stem.2020.06.015.
[20]	ZHAO B, NI C, GAO R, et al. Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids[J]. Protein Cell, 2020, 11(10): 771-775. DOI: 10.1007/s13238-020-00718-6.
[21]	HAN D, FANG Q, WANG X. SARS-CoV-2 was found in the bile juice from a patient with severe COVID-19[J]. J Med Virol, 2021, 93(1): 102-104. DOI: 10.1002/jmv.26169.
[22]	QI F, QIAN S, ZHANG S, et al. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses[J]. Biochem Biophys Res Commun, 2020, 526(1): 135-140. DOI: 10.1016/j.bbrc.2020.03.044.
[23]	SCOTT CL, ZHENG F, de BAETSELIER P, et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells[J]. Nat Commun, 2016, 7: 10321. DOI: 10.1038/ncomms10321.
[24]	ABASSI Z, KNANEY Y, KARRAM T, et al. The Lung Macrophage in SARS-CoV-2 Infection: A Friend or a Foe?[J]. Front Immunol, 2020, 11: 1312. DOI: 10.3389/fimmu.2020.01312.
[25]	LAX SF, SKOK K, ZECHNER P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: Results from a prospective, single-center, clinicopathologic case series[J]. Ann Intern Med, 2020, 173(5): 350-361. DOI: 10.7326/M20-2566.
[26]	MOON AM, WEBB GJ, ALOMAN C, et al. High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: Preliminary results from an international registry[J]. J Hepatol, 2020, 73(3): 705-708. DOI: 10.1016/j.jhep.2020.05.013.
[27]	DE MINICIS S, SEKI E, UCHINAMI H, et al. Gene expression profiles during hepatic stellate cell activation in culture and in vivo[J]. Gastroenterology, 2007, 132(5): 1937-1946. DOI: 10.1053/j.gastro.2007.02.033.
[28]	MEHTA P, MCAULEY DF, BROWN M, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression[J]. Lancet, 2020, 395(10229): 1033-1034. DOI: 10.1016/S0140-6736(20)30628-0.
[29]	QIN C, ZHOU L, HU Z, et al. Dysregulation of immune response in patients with coronavirus 2019(COVID-19) in Wuhan, China[J]. Clin Infect Dis, 2020, 71(15): 762-768. DOI: 10.1093/cid/ciaa248.
[30]	DIAO B, WANG C, TAN Y, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019(COVID-19)[J]. Front Immunol, 2020, 11: 827. DOI: 10.3389/fimmu.2020.00827.
[31]	HU WJ, CHEN TL, YAN YJ, et al. Clinical indicators of 44 patients with different types of coronavirus disease 2019[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2021, 15(1): 15-21. DOI: 10.3877/cma.j.issn.1674-1358.2021.01.004. 胡文佳, 陈铁龙, 严亚军, 等. 44例不同严重程度新型冠状病毒肺炎患者临床检测指标分析[J/CD]. 中华实验和临床感染病杂志(电子版), 2021, 15(1): 15-21. DOI: 10.3877/cma.j.issn.1674-1358.2021.01.004.
[32]	HORVATITS T, DROLZ A, TRAUNER M, et al. Liver injury and failure in critical illness[J]. Hepatology, 2019, 70(6): 2204-2215. DOI: 10.1002/hep.30824.
[33]	YANG X, YU Y, XU J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study[J]. Lancet Respir Med, 2020, 8(5): 475-481. DOI: 10.1016/S2213-2600(20)30079-5.
[34]	SHAHRBAF MA, TABARY M, KHAHESHI I. The right ventricle in COVID-19 patients[J]. Eur Heart J, 2021, 42(6): 559-560. DOI: 10.1093/eurheartj/ehaa832.
[35]	GRILLET F, BEHR J, CALAME P, et al. Acute pulmonary embolism associated with COVID-19 pneumonia detected with pulmonary CT angiography[J]. Radiology, 2020, 296(3): E186-E188. DOI: 10.1148/radiol.2020201544.
[36]	KULKARNI AV, KUMAR P, TEVETHIA HV, et al. Systematic review with meta-analysis: Liver manifestations and outcomes in COVID-19[J]. Aliment Pharmacol Ther, 2020, 52(4): 584-599. DOI: 10.1111/apt.15916.
[37]	ZHANG C, WU Z, LI JW, et al. Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality[J]. Int J Antimicrob Agents, 2020, 55(5): 105954. DOI: 10.1016/j.ijantimicag.2020.105954.
[38]	MUHOVIĆ D, BOJOVIĆ J, BULATOVIĆ A, et al. First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19[J]. Liver Int, 2020, 40(8): 1901-1905. DOI: 10.1111/liv.14516.
[39]	SEBBA A. Tocilizumab: The first interleukin-6-receptor inhibitor[J]. Am J Health Syst Pharm, 2008, 65(15): 1413-1418. DOI: 10.2146/ajhp070449.
[40]	ZHANG H, LI HB, LYU JR, et al. Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection[J]. Int J Infect Dis, 2020, 96: 19-24. DOI: 10.1016/j.ijid.2020.04.027.
[41]	NARDO AD, SCHNEEWEISS-GLEIXNER M, BAKAIL M, et al. Pathophysiological mechanisms of liver injury in COVID-19[J]. Liver Int, 2021, 41(1): 20-32. DOI: 10.1111/liv.14730.
[42]	LAI ZX, FAN YM, OU JY, et al. Diagnosis and treatment of COVID-19 pneumonia complicated with bacterial and fungal infection[J]. J Prac Med, 2021, 37(1): 16-19. DOI: 10.3969/j.issn.1006-5725.2021.01.004. 赖展翔, 范颖敏, 区静怡, 等. 新型冠状病毒肺炎合并细菌及真菌感染的诊疗特点[J]. 实用医学杂志, 2021, 37(1): 16-19. DOI: 10.3969/j.issn.1006-5725.2021.01.004.
[43]	LANSBURY L, LIM B, BASKARAN V, et al. Co-infections in people with COVID-19: A systematic review and meta-analysis[J]. J Infect, 2020, 81(2): 266-275. DOI: 10.1016/j.jinf.2020.05.046.
[44]	FELDMAN C, ANDERSON R. The role of co-infections and secondary infections in patients with COVID-19[J]. Pneumonia, 2021, 13(1): 5. DOI: 10.1186/s41479-021-00083-w.
[45]	China Digestion Association, Chinese Medical Doctor Association; Chinese Society of Hepatology, Chinese Medical Association. The protocol for prevention, diagnosis and treatment of liver injury in coronavirus disease 2019[J]. J Clin Hepatol, 2020, 36(4): 754-757. DOI: 10.3969/j.issn.1001-5256.2020.04.008. 中国医师协会消化医师分会, 中华医学会肝病学分会. 新型冠状病毒肺炎合并肝脏损伤的预防及诊疗方案[J]. 临床肝胆病杂志, 2020, 36(4): 754-757. DOI: 10.3969/j.issn.1001-5256.2020.04.008.
[46]	HUANG A, YANG XR, SUN HC, et al. Mechanism and prevention and treatment of liver injury associated with new coronavirus pneumonia[J]. Chin J Dig Surg, 2020, 19(3): 248-250. DOI: 10.3760/cma.j.issn.1673-9752.2020.03.006. 黄傲, 杨欣荣, 孙惠川, 等. 新型冠状病毒肺炎相关肝损伤的发生机制及防治措施[J]. 中华消化外科杂志, 2020, 19(3): 248-250. DOI: 10.3760/cma.j.issn.1673-9752.2020.03.006.
[47]	SUN J, AGHEMO A, FORNER A, et al. COVID-19 and liver disease[J]. Liver Int, 2020, 40(6): 1278-1281. DOI: 10.1111/liv.14470.
[48]	SAHIN TT, AKBULUT S, YILMAZ S. COVID-19 pandemic: Its impact on liver disease and liver transplantation[J]. World J Gastroenterol, 2020, 26(22): 2987-2999. DOI: 10.3748/wjg.v26.i22.2987.
[49]	RABIEE A, SADOWSKI B, ADENIJI N, et al. Liver injury in liver transplant recipients with coronavirus disease 2019(COVID-19): U.S. multicenter experience[J]. Hepatology, 2020, 72(6): 1900-1911. DOI: 10.1002/hep.31574.