终末期肝病合并感染诊治专家共识(2021年版)

中华医学会感染病学分会

doi:10.3969/j.issn.1001-5256.2022.02.010

终末期肝病合并感染诊治专家共识(2021年版)

DOI: 10.3969/j.issn.1001-5256.2022.02.010

中华医学会感染病学分会

利益冲突声明：所有作者均声明不存在利益冲突。

宁琴，qning@vip.sina.com；王贵强，john131212@sina.com

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出版历程
- 收稿日期: 2022-01-29
- 录用日期: 2022-01-31
- 出版日期: 2022-02-20

Expert consensus on diagnosis and treatment of end-stage liver disease complicated with infections(2021 version)

Society of Infectious Diseases

摘要

摘要: 终末期肝病(end-stage liver disease，ESLD)发生发展中，感染可以诱发或加重ESLD肝功能失代偿的发生，亦是ESLD发展过程中最易出现的并发症之一。ESLD合并感染的规范诊疗需求迫切，2018年7月, 中华医学会感染病学分会制订了我国第一部《终末期肝病合并感染诊治专家共识》，基于2018年至今的循证医学数据及治疗方案，进行本次修订。本共识旨在指导并提高临床医务工作者对ESLD合并感染疾病的综合诊治能力。
- 终末期肝病 /
- 感染 /
- 诊断 /
- 治疗 /
- 共识
Abstract: End-stage liver disease (ESLD) is a life-threatening clinical syndrome with significantly increased mortality when the patients are complicated with infections. For patients with ESLD, infections can induce or aggravate the liver decompensation. In turn, infections are among the most common complication with the disease progression. Experts from Society of Infectious Diseases, Chinese Medical Association firstly formulated "Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infection" in July 2018, which is extensively revised based on clinical evidence of recent three years. This consensus summarizes the up-to-date knowledge and experiences across Chinese colleagues, intending to provide principles and wording procedures for clinicians to diagnose and treat ESLD patient complicated with infections.
- End-Stage Liver Disease /
- Infection /
- Diagnosis /
- Treatment /
- Consensus

HTML全文

表 1 ESLD合并感染的常见病原体^[11-13]

感染部位	常见病原体
腹腔	大肠埃希菌、肺炎克雷伯菌、肠球菌、厌氧菌、白念珠菌
呼吸道	肺炎链球菌、流感嗜血杆菌、肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌、金黄色葡萄球菌、曲霉菌
泌尿道	大肠埃希菌、肺炎克雷伯菌、粪肠球菌、屎肠球菌、白念珠菌
胃肠道	大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌、屎肠球菌、粪肠球菌、白念珠菌
胆道	大肠埃希菌、肺炎克雷伯菌、肠球菌、白念珠菌
皮肤软组织	葡萄球菌、链球菌、肠杆菌
血流	大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌、屎肠球菌、粪肠球菌、念珠菌

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感染类型	推荐治疗方案
社区获得性	哌拉西林/他唑巴坦、第三代头孢菌素、环丙沙星、左氧氟沙星
医院获得性	碳青霉烯类单用；或联用万古霉素、利奈唑胺(革兰阳性菌MDR高流行区域，或合并脓毒症)

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感染类型	推荐治疗方案
社区获得性	哌拉西林他唑巴坦、第三代头孢菌素、左氧氟沙星
医院获得性	哌拉西林他唑巴坦、第三代头孢菌素或美罗培南+万古霉素或利奈唑胺抗生素相关性腹泻，可酌情给予制霉菌素口服或万古霉素口服(艰难梭菌)

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感染类型	推荐治疗方案
社区获得性	哌拉西林他唑巴坦、第三代头孢菌素、左氧氟沙星
医院获得性	哌拉西林他唑巴坦、第三代头孢菌素或美罗培南+万古霉素或利奈唑胺抗生素相关性腹泻，可酌情给予制霉菌素口服或万古霉素口服(艰难梭菌)

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感染类型	推荐治疗方案
社区获得性	单纯性下尿路感染：呋喃妥因、复方新诺明、环丙沙星
	复杂性或上尿路感染或合并脓毒血症：哌拉西林/他唑巴坦、第三代头孢菌素、厄他培南
医院获得性	单纯性下尿路感染：阿莫西林/克拉维酸、哌拉西林/他唑巴坦
	复杂性或上尿路感染或合并脓毒血症：碳青霉烯类联合或不联合替考拉宁或万古霉素

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感染类型	推荐治疗方案
非化脓性(蜂窝织炎/丹毒)	轻度：外用药物(莫匹罗星)、口服治疗(青霉素Ⅴ、Ⅰ~Ⅲ代头孢菌素、喹诺酮类)
	中重度：静脉注射治疗(青霉素G、Ⅲ代头孢菌素、喹诺酮类)
化脓性(疖/痈/脓肿)	轻中度：外科处理、口服复方磺胺甲基异噁唑、口服耐酶青霉素重度：非MRSA感染(头孢唑林、头孢呋辛、耐酶青霉素等)；MRSA感染(万古霉素或达托霉素或利奈唑胺)，静脉滴注治疗

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表 2 ESLD合并不同部位侵袭性真菌病的经验性抗感染治疗药物推荐

感染部位	病原类型	推荐药物
腹腔	念珠菌、曲霉菌	卡泊芬净、米卡芬净、伏立康唑
呼吸道	曲霉菌、念珠菌	卡泊芬净、米卡芬净、氟康唑、伏立康唑
泌尿道	念珠菌	氟康唑、两性霉素B脂质体
皮肤软组织	念珠菌	外用药物：克霉唑、益康唑、咪康唑、酮康唑
		全身用药：氟康唑、伊曲康唑
血流	念珠菌、曲霉菌	卡泊芬净、米卡芬净、氟康唑、伏立康唑、两性霉素B脂质体
颅内	念珠菌、曲霉菌、隐球菌	氟康唑、伏立康唑、两性霉素B脂质体

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表 3 常见抗真菌药物对于肝损伤患者的剂量调整

抗真菌药物	正常肝功能	Child-Pugh分级
抗真菌药物	正常肝功能	A级(5~6分)	B级(7~9分)	C级(≥10分)
两性霉素B	初治1~5 mg给药，每日或隔日增加5 mg，当增致一次0.6~0.7/kg时即可暂停增加剂量	不推荐	不推荐	不推荐
氟康唑	400 mg，1次/d	400 mg，1次/d	400 mg，1次/d	200~400 mg，1次/d
伊曲康唑	200 mg，1次/12 h，第一天200 mg/d	200 mg，1次/12 h，第一天200 mg/d	200 mg，1次/12 h，第一天200 mg/d	200 mg，1次/12 h，第一天200 mg/d
伏立康唑	6 mg/kg，1次/12 h，第一天4 mg/kg，1次/12 h	6 mg/kg，1次/12 h，第一天2 mg/kg，1次/12 h	6 mg/kg，1次/12 h，第一天2 mg/kg，1次/12 h	不推荐
泊沙康唑	200 mg，1次/8 h	200 mg，1次/8 h	200 mg，1次/8 h	200 mg，1次/8 h
卡泊芬净	70 mg，1次/d，第一天50 mg，1次/d	70 mg，1次/d，第一天50 mg，1次/d	70 mg，1次/d，第一天35 mg，1次/d	不推荐
米卡芬净	100 mg/d	100 mg/d	100 mg/d	100 mg/d
阿尼芬净	100 mg/d	100 mg/d	100 mg/d	100 mg/d
注：A级(5~6分)，轻度肝脏损害；B级(7~9分)，中度肝脏损害；C级(≥10分)，重度肝脏损害。

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参考文献(130)

[1]	HOUSSIN D, FRANCO D, CORLETTE MB, et al. Criteria for hepatic transplantation in cirrhosis[J]. Surg Gynecol Obstet, 1980, 151(1): 30-32.
[2]	OTTE JB, DE HEMPTINE B, MOULIN D, et al. Liver transplantation in children[J]. Chir Pediatr, 1985, 26(5): 261-273.
[3]	CHEN T, NING Q. Highlights of diagnosis and treatment for end stage of liver disease with infection[J]. Chin J Clin Infect Dis, 2017, 10(5): 389-393. DOI: 10.3760/cma.j.issn.1674-2397.2017.05.014. 陈韬, 宁琴. 终末期肝病合并感染诊治的热点与难点[J]. 中华临床感染病杂志, 2017, 10(5): 389-393. DOI: 10.3760/cma.j.issn.1674-2397.2017.05.014.
[4]	ARVANITI V, D'AMICO G, FEDE G, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis[J]. Gastroenterology, 2010, 139(4): 1246-1256. e1-5. DOI: 10.1053/j.gastro.2010.06.019.
[5]	WONG F, PIANO S, SINGH V, et al. Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure[J]. J Hepatol, 2021, 74(2): 330-339. DOI: 10.1016/j.jhep.2020.07.046.
[6]	CAO ZJ, LIU YH, ZHU CW, et al. Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study[J]. World J Gastroenterol, 2020, 26(6): 645-656. DOI: 10.3748/wjg.v26.i6.645.
[7]	JHA AK, NIJHAWAN S, SUCHISMITA A. Sepsis in acute on chronic liver failure[J]. Dig Dis Sci, 2011, 56(4): 1245-1246. DOI: 10.1007/s10620-011-1605-2.
[8]	YANG L, WU T, LI J, et al. Bacterial infections in acute-on-chronic liver failure[J]. Semin Liver Dis, 2018, 38(2): 121-133. DOI: 10.1055/s-0038-1657751.
[9]	FERNÁNDEZ J, ACEVEDO J, WIEST R, et al. Bacterial and fungal infections in acute-on-chronic liver failure: Prevalence, characteristics and impact on prognosis[J]. Gut, 2018, 67(10): 1870-1880. DOI: 10.1136/gutjnl-2017-314240.
[10]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis[J]. J Hepatol, 2018, 69(2): 406-460. DOI: 10.1016/j.jhep.2018.03.024.
[11]	EKPANYAPONG S, REDDY KR. Infections in cirrhosis[J]. Curr Treat Options Gastroenterol, 2019, 17(2): 254-270. DOI: 10.1007/s11938-019-00229-2.
[12]	JALAN R, FERNANDEZ J, WIEST R, et al. Bacterial infections in cirrhosis: A position statement based on the EASL Special Conference 2013[J]. J Hepatol, 2014, 60(6): 1310-1324. DOI: 10.1016/j.jhep.2014.01.024.
[13]	KURUP A, LIAU KH, REN J, et al. Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective[J]. Ann Med Surg (Lond), 2014, 3(3): 85-91. DOI: 10.1016/j.amsu.2014.06.005.
[14]	SALERNO F, BORZIO M, PEDICINO C, et al. The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study[J]. Liver Int, 2017, 37(1): 71-79. DOI: 10.1111/liv.13195.
[15]	VIVAS R, BARBOSA A, DOLABELA SS, et al. Multidrug-resistant bacteria and alternative methods to control them: An overview[J]. Microb Drug Resist, 2019, 25(6): 890-908. DOI: 10.1089/mdr.2018.0319.
[16]	CASULLERAS M, ZHANG IW, LÒPEZ-VICARIO C, et al. Leukocytes, systemic inflammation and immunopathology in acute-on-chronic liver failure[J]. Cells, 2020, 9(12): 2632. DOI: 10.3390/cells9122632.
[17]	ALBILLOS A, DE GOTTARDI A, RESCIGNO M. The gut-liver axis in liver disease: Pathophysiological basis for therapy[J]. J Hepatol, 2020, 72(3): 558-577. DOI: 10.1016/j.jhep.2019.10.003.
[18]	CHOUDHURY A, KUMAR M, SHARMA BC, et al. Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study[J]. J Gastroenterol Hepatol, 2017, 32(12): 1989-1997. DOI: 10.1111/jgh.13799.
[19]	CLÀRIA J, STAUBER RE, COENRAAD MJ, et al. Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure[J]. Hepatology, 2016, 64(4): 1249-1264. DOI: 10.1002/hep.28740.
[20]	WONG CL, HOLROYD-LEDUC J, THORPE KE, et al. Does this patient have bacterial peritonitis or portal hypertension? How do I perform a paracentesis and analyze the results?[J]. JAMA, 2008, 299(10): 1166-1178. DOI: 10.1001/jama.299.10.1166.
[21]	RIGHI E. Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions[J]. World J Gastroenterol, 2018, 24(38): 4311-4329. DOI: 10.3748/wjg.v24.i38.4311.
[22]	ASCIONE T, DI FLUMERI G, BOCCIA G, et al. Infections in patients affected by liver cirrhosis: An update[J]. Infez Med, 2017, 25(2): 91-97.
[23]	LUO WQ, ZHANG DZ. Diagnosis and treatment of bacterial infection in patients with end-stage liver disease[J]. Chin J Hepatol, 2018, 26(1): 10-12. DOI: 10.3760/cma.j.issn.1007-3418.2018.01.004. 罗文强, 张大志. 终末期肝病患者合并细菌感染的诊断与治疗[J]. 中华肝脏病杂志, 2018, 26(1): 10-12. DOI: 10.3760/cma.j.issn.1007-3418.2018.01.004.
[24]	DING SN, DU N, YANG WM, et al. The current status of bacterial infections and management in decompensated cirrhosis[J]. Chin J Hepatol, 2014, 22(11): 863-865. DOI: 10.3760/cma.j.issn.1007-3418.2014.011.013. 丁胜楠, 杜娜, 杨伟民, 等. 肝硬化失代偿期患者细菌感染及治疗现状[J]. 中华肝脏病杂志, 2014, 22(11): 863-865. DOI: 10.3760/cma.j.issn.1007-3418.2014.011.013.
[25]	YANG ZY, CHEN T. Diagnosis and treatment of liver failure complicated with fungal infection[J]. J Inter Intens Med, 2019, 25(3): 185-188. DOI: 10.11768/nkjwzzzz20190303. 杨中原, 陈韬. 肝衰竭合并真菌感染的诊断和治疗[J]. 内科急危重症杂志, 2019, 25(3): 185-188. DOI: 10.11768/nkjwzzzz20190303.
[26]	MOLDOVEANU B, GEARHART AM, JALIL BA, et al. Pulmonary aspergillosis: Spectrum of disease[J]. Am J Med Sci, 2021, 361(4): 411-419. DOI: 10.1016/j.amjms.2020.12.009.
[27]	CHABI ML, GORACCI A, ROCHE N, et al. Pulmonary aspergillosis[J]. Diagn Interv Imaging, 2015, 96(5): 435-442. DOI: 10.1016/j.diii.2015.01.005.
[28]	PARK JW, LEE JK, LEE KT, et al. How to interpret the bile culture results of patients with biliary tract infections[J]. Clin Res Hepatol Gastroenterol, 2014, 38(3): 300-309. DOI: 10.1016/j.clinre.2014.02.005.
[29]	CATALANO OA, SAHANI DV, FORCIONE DG, et al. Biliary infections: Spectrum of imaging findings and management[J]. Radiographics, 2009, 29(7): 2059-2080. DOI: 10.1148/rg.297095051.
[30]	HODGES K, HECHT G. Bacterial infections of the small intestine[J]. Curr Opin Gastroenterol, 2013, 29(2): 159-163. DOI: 10.1097/MOG.0b013e32835b422c.
[31]	BARTOLETTI M, GIANNELLA M, CARACENI P, et al. Epidemiology and outcomes of bloodstream infection in patients with cirrhosis[J]. J Hepatol, 2014, 61(1): 51-58. DOI: 10.1016/j.jhep.2014.03.021.
[32]	ZHAO H, GU X, ZHAO R, et al. Evaluation of prognostic scoring systems in liver cirrhosis patients with bloodstream infection[J]. Medicine (Baltimore), 2017, 96(50): e8844. DOI: 10.1097/MD.0000000000008844.
[33]	XIE Y, TU B, ZHANG X, et al. Investigation on outcomes and bacterial distributions of liver cirrhosis patients with gram-negative bacterial bloodstream infection[J]. Oncotarget, 2018, 9(3): 3980-3995. DOI: 10.18632/oncotarget.23582.
[34]	XIE Y, TU B, XU Z, et al. Bacterial distributions and prognosis of bloodstream infections in patients with liver cirrhosis[J]. Sci Rep, 2017, 7(1): 11482. DOI: 10.1038/s41598-017-11587-1.
[35]	LIANG LF, ZHOU ZG, LEI Y, et al. Clinical analysis of 154 blood stream infection patients with decompensated liver cirrhosis[J]. Chin J Infect Chemoth, 2016, 16(3): 262-266. DOI: 10.16718/j.1009-7708.2016.03.005. 梁丽芬, 周召刚, 雷宇, 等. 154例肝硬化失代偿期患者并发血流感染的临床分析[J]. 中国感染与化疗杂志, 2016, 16(3): 262-266. DOI: 10.16718/j.1009-7708.2016.03.005.
[36]	EL-AMIN H, SABRY A, AHMED RE, et al. Types and microbiological spectrum of infections in patients with cirrhosis: A single-centre experience in Upper Egypt[J]. Arab J Gastroenterol, 2017, 18(3): 159-164. DOI: 10.1016/j.ajg.2017.09.005.
[37]	LIU BM, CHUNG KJ, CHEN CH, et al. Risk factors for the outcome of cirrhotic patients with soft tissue infections[J]. J Clin Gastroenterol, 2008, 42(3): 312-316. DOI: 10.1097/MCG.0b013e31802dbde8.
[38]	BAJAJ JS, FAGAN A, SIKAROODI M, et al. Alterations in skin microbiomes of patients with cirrhosis[J]. Clin Gastroenterol Hepatol, 2019, 17(12): 2581-2591. e15. DOI: 10.1016/j.cgh.2019.03.028.
[39]	SU CM, CHANG WN, TSAI NW, et al. Clinical features and outcome of community-acquired bacterial meningitis in adult patients with liver cirrhosis[J]. Am J Med Sci, 2010, 340(6): 452-456. DOI: 10.1097/MAJ.0b013e3181ee988d.
[40]	BARAHONA-GARRIDO J, HERNÁNDEZ-CALLEROS J, TÉLLEZ-AVILA FI, et al. Bacterial meningitis in cirrhotic patients: Case series and description of the prognostic role of acute renal failure[J]. J Clin Gastroenterol, 2010, 44(9): e218-e223. DOI: 10.1097/MCG.0b013e3181d88d53.
[41]	PAGLIANO P, BOCCIA G, DE CARO F, et al. Bacterial meningitis complicating the course of liver cirrhosis[J]. Infection, 2017, 45(6): 795-800. DOI: 10.1007/s15010-017-1039-7.
[42]	EPSTEIN O, DICK R, SHERLOCK S. Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease[J]. Gut, 1981, 22(3): 203-206. DOI: 10.1136/gut.22.3.203.
[43]	ALLAIRE M, CADRANEL JD, BUREAU C, et al. Severe liver failure rather than cirrhosis is associated with mortality in patients with infectious endocarditis: A retrospective case-control study[J]. Eur J Gastroenterol Hepatol, 2018, 30(10): 1216-1223. DOI: 10.1097/MEG.0000000000001155.
[44]	RUIZ-MORALES J, IVANOVA-GEORGIEVA R, FERNÁNDEZ-HIDALGO N, et al. Left-sided infective endocarditis in patients with liver cirrhosis[J]. J Infect, 2015, 71(6): 627-641. DOI: 10.1016/j.jinf.2015.09.005.
[45]	IOANNOU P, SAVVA E, KOFTERIDIS DP. Infective endocarditis in patients with liver cirrhosis: A systematic review[J]. J Chemother, 2021, 33(7): 443-451. DOI: 10.1080/1120009X.2021.1878332.
[46]	LEE S, UM T, JOE SG, et al. Changes in the clinical features and prognostic factors of endogenous endophthalmitis: Fifteen years of clinical experience in Korea[J]. Retina, 2012, 32(5): 977-984. DOI: 10.1097/IAE.0b013e318228e312.
[47]	CHUNG KS, KIM YK, SONG YG, et al. Clinical review of endogenous endophthalmitis in Korea: A 14-year review of culture positive cases of two large hospitals[J]. Yonsei Med J, 2011, 52(4): 630-634. DOI: 10.3349/ymj.2011.52.4.630.
[48]	DANIELESCU C, ANTON N, STANCA HT, et al. Endogenous endophthalmitis: A review of case series published between 2011 and 2020[J]. J Ophthalmol, 2020, 2020: 8869590. DOI: 10.1155/2020/8869590.
[49]	HE X, GAO Y, LIU Q, et al. Diagnostic value of interferon-gamma release assays combined with multiple indicators for tuberculous peritonitis[J]. Gastroenterol Res Pract, 2020, 2020: 2056168. DOI: 10.1155/2020/2056168.
[50]	BESSER J, CARLETON HA, GERNER-SMIDT P, et al. Next-generation sequencing technologies and their application to the study and control of bacterial infections[J]. Clin Microbiol Infect, 2018, 24(4): 335-341. DOI: 10.1016/j.cmi.2017.10.013.
[51]	LUO Y, XUE Y, MAO L, et al. Diagnostic value of T-SPOT. TB assay for tuberculous peritonitis: A meta-analysis[J]. Front Med (Lausanne), 2020, 7: 585180. DOI: 10.3389/fmed.2020.585180.
[52]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease[J]. J Hepatol, 2019, 70(1): 172-193. DOI: 10.1016/j.jhep.2018.06.024.
[53]	TANDON P, RAMAN M, MOURTZAKIS M, et al. A practical approach to nutritional screening and assessment in cirrhosis[J]. Hepatology, 2017, 65(3): 1044-1057. DOI: 10.1002/hep.29003.
[54]	CRUZ-JENTOFT AJ, BAHAT G, BAUER J, et al. Sarcopenia: Revised European consensus on definition and diagnosis[J]. Age Ageing, 2019, 48(1): 16-31. DOI: 10.1093/ageing/afy169.
[55]	Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Gastroenterology, Chinese Medical Association. Clinical guidelines on nutrition in end-stage liver disease[J]. J Clin Hepatol, 2019, 35(6): 1222-1230. DOI: 10.3969/j.issn.1001-5256.2019.06.010. 中华医学会肝病学分会, 中华医学会消化病学分会. 终末期肝病临床营养指南[J]. 临床肝胆病杂志, 2019, 35(6): 1222-1230. DOI: 10.3969/j.issn.1001-5256.2019.06.010.
[56]	BISCHOFF SC, BERNAL W, DASARATHY S, et al. ESPEN practical guideline: Clinical nutrition in liver disease[J]. Clin Nutr, 2020, 39(12): 3533-3562. DOI: 10.1016/j.clnu.2020.09.001.
[57]	Beijing Medical Association, Committee of Parenteral and Enteral Nutrition; Expert Panel on Consensus on the parenteral and Enteral Nutritional and the Dietary Intervention for Patients with Chronic Liver Diseases. Consensus on the clinical nutritional intervention for patients with chronic liver diseases[J]. J Clin Hepatol, 2017, 33(7): 1236-1245. DOI: 10.3969/j.issn.1001-5256.2017.07.006. 北京医学会肠外肠内营养学专业委员会, 《慢性肝病患者肠外肠内营养支持与膳食干预专家共识》专家委员会. 慢性肝病患者肠外肠内营养支持与膳食干预专家共识[J]. 临床肝胆病杂志, 2017, 33(7): 1236-1245. DOI: 10.3969/j.issn.1001-5256.2017.07.006.
[58]	BUNCHORNTAVAKUL C, REDDY KR. Review article: Malnutrition/sarcopenia and frailty in patients with cirrhosis[J]. Aliment Pharmacol Ther, 2020, 51(1): 64-77. DOI: 10.1111/apt.15571.
[59]	Society of Infectious Diseases, Chinese Medical Association; Expert Committee for Prevention and Management of Liver inflammation. Consensus statement by the expert committee for prevention and management of liver inflammation in China[J]. Chin J Pract Intern Med, 2014, 34(2): 152-162. 中华医学会感染病学分会, 肝脏炎症及其防治专家共识专家委员会. 肝脏炎症及其防治专家共识[J]. 中国实用内科杂志, 2014, 34(2): 152-162.
[60]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.
[61]	Chinese Society of Internal Medicine, Chinese Medical Association, WANG JX, ZHANG FC, et al. Expert consensus for diagnosis and treatment of thrombocytopenia in China[J]. Chin J Intern Med, 2020, 59(7): 498-510. DOI: 10.3760/cma.j.cn112138-20200424-00419. 中华医学会内科学分会, 王建祥, 张奉春, 等. 中国成人血小板减少症诊疗专家共识[J]. 中华内科杂志, 2020, 59(7): 498-510. DOI: 10.3760/cma.j.cn112138-20200424-00419.
[62]	MARUYAMA T, MURATA S, TAKAHASHI K, et al. Platelet transfusion improves liver function in patients with chronic liver disease and cirrhosis[J]. Tohoku J Exp Med, 2013, 229(3): 213-220. DOI: 10.1620/tjem.229.213.
[63]	TERRAULT N, CHEN YC, IZUMI N, et al. Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia[J]. Gastroenterology, 2018, 155(3): 705-718. DOI: 10.1053/j.gastro.2018.05.025.
[64]	ZHANG HF, WANG LM, DONG Y, et al. A clinical study on Leucogen tablets therapy efficacy during PEGα-Interferon and α-Interferon in chronic hepatitis B[J]. Chin J Exp Clin Virol, 2012, 26(2): 111-113. DOI: 10.3760/cma.j.issn.1003-9279.2012.02.011. 张鸿飞, 王丽旻, 董漪, 等. 慢性乙型肝炎患者聚乙二醇α干扰素与α干扰素治疗中应用利可君的临床研究[J]. 中华实验和临床病毒学杂志, 2012, 26(2): 111-113. DOI: 10.3760/cma.j.issn.1003-9279.2012.02.011.
[65]	LIU BW, XIANG HL, LIANG J, et al. Comparison of efficacy of recombinant human interleukin-11 and recombinant human thrombopoietin in treating thrombocytopenia with hypersplenism in cirrhotic patients[J]. World Chin J Dig, 2016, 24(34): 4608-4614. DOI: 10.11569/wcjd.v24.i34.4608. 刘保文, 向慧玲, 梁静, 等. 重组人白介素-11及重组人血小板生成素在治疗肝硬化脾功能亢进所致血小板减少的疗效对比[J]. 世界华人消化杂志, 2016, 24(34): 4608-4614. DOI: 10.11569/wcjd.v24.i34.4608.
[66]	ZACCHERINI G, TUFONI M, BERNARDI M. Albumin administration is efficacious in the management of patients with cirrhosis: A systematic review of the literature[J]. Hepat Med, 2020, 12: 153-172. DOI: 10.2147/HMER.S264231.
[67]	ROMANELLI RG, LA VILLA G, BARLETTA G, et al. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: An unblinded randomized trial[J]. World J Gastroenterol, 2006, 12(9): 1403-1407. DOI: 10.3748/wjg.v12.i9.1403.
[68]	DWYER JM. Intravenous therapy with gamma globulin[J]. Adv Intern Med, 1987, 32: 111-135.
[69]	CHEN JF, CHEN SR, LEI ZY, et al. Thymosin alpha 1 for patients with hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial[J]. J Hepatology, 2020, 73: S498-S499.
[70]	PENG D, XING HY, LI C, et al. The clinical efficacy and adverse effects of Entecavir plus Thymosin alpha-1 combination therapy versus Entecavir Monotherapy in HBV-related cirrhosis: A systematic review and meta-analysis[J]. BMC Gastroenterol, 2020, 20(1): 348. DOI: 10.1186/s12876-020-01477-8.
[71]	XU D, ZHAO M, SONG Y, et al. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: Review on the effects of GM-CSF in maintaining homeostasis of the immune system[J]. Hepatol Int, 2015, 9(1): 28-34. DOI: 10.1007/s12072-014-9588-7.
[72]	HAMILTON JA. GM-CSF as a target in inflammatory/autoimmune disease: Current evidence and future therapeutic potential[J]. Expert Rev Clin Immunol, 2015, 11(4): 457-465. DOI: 10.1586/1744666X.2015.1024110.
[73]	VERMA N, KAUR A, SHARMA R, et al. Outcomes after multiple courses of granulocyte colony-stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial[J]. Hepatology, 2018, 68(4): 1559-1573. DOI: 10.1002/hep.29763.
[74]	DE A, KUMARI S, SINGH A, et al. Multiple cycles of granulocyte colony-stimulating factor increase survival times of patients with decompensated cirrhosis in a randomized trial[J]. Clin Gastroenterol Hepatol, 2021, 19(2): 375-383. e5. DOI: 10.1016/j.cgh.2020.02.022.
[75]	JIA L, XUE R, ZHU Y, et al. The efficacy and safety of methylprednisolone in hepatitis B virus-related acute-on-chronic liver failure: A prospective multi-center clinical trial[J]. BMC Med, 2020, 18(1): 383. DOI: 10.1186/s12916-020-01814-4.
[76]	CHEN F, SHI Y, LIU X, et al. Corticosteroid improves liver function but does not curb the clinical progression of hepatitis B virus-related acute-on-chronic pre-liver failure[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(11): 1129-1135. DOI: 10.1080/17474124.2019.1688143.
[77]	SARIN SK, CHOUDHURY A, SHARMA MK, et al. Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific association for the study of the liver (APASL): An update[J]. Hepatol Int, 2019, 13(4): 353-390. DOI: 10.1007/s12072-019-09946-3.
[78]	TOYODA H, LEONG J, LANDIS C, et al. treatment and renal outcomes up to 96 weeks after tenofovir alafenamide switch from tenofovir disoproxil fumarate in routine practice[J]. Hepatology, 2021, 74(2): 656-666. DOI: 10.1002/hep.31793.
[79]	FARAG MS, FUNG S, TAM E, et al. Effectiveness and renal safety of tenofovir alafenamide fumarate among chronic hepatitis B patients: Real-world study[J]. J Viral Hepat, 2021, 28(6): 942-950. DOI: 10.1111/jvh.13500.
[80]	LEGGIO L, KENNA GA, FERRULLI A, et al. Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease[J]. Hum Psychopharmacol, 2011, 26(8): 554-559. DOI: 10.1002/hup.1244.
[81]	SHIZUMA T. Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review[J]. World J Hepatol, 2018, 10(2): 254-266. DOI: 10.4254/wjh.v10.i2.254.
[82]	PIANO S, BROCCA A, MARESO S, et al. Infections complicating cirrhosis[J]. Liver Int, 2018, 38 Suppl 1: 126-133. DOI: 10.1111/liv.13645.
[83]	SHI L, WU D, WEI L, et al. Nosocomial and community-acquired spontaneous bacterial peritonitis in patients with liver cirrhosis in China: Comparative microbiology and therapeutic implications[J]. Sci Rep, 2017, 7: 46025. DOI: 10.1038/srep46025.
[84]	DEVER JB, SHEIKH MY. Review article: Spontaneous bacterial peritonitis--bacteriology, diagnosis, treatment, risk factors and prevention[J]. Aliment Pharmacol Ther, 2015, 41(11): 1116-1131. DOI: 10.1111/apt.13172.
[85]	FIORE M, LEONE S. Spontaneous fungal peritonitis: Epidemiology, current evidence and future prospective[J]. World J Gastroenterol, 2016, 22(34): 7742-7747. DOI: 10.3748/wjg.v22.i34.7742.
[86]	HWANG SY, YU SJ, LEE JH, et al. Spontaneous fungal peritonitis: A severe complication in patients with advanced liver cirrhosis[J]. Eur J Clin Microbiol Infect Dis, 2014, 33(2): 259-264. DOI: 10.1007/s10096-013-1953-2.
[87]	HASSAN EA, ABD EL-REHIM AS, HASSANY SM, et al. Fungal infection in patients with end-stage liver disease: Low frequency or low index of suspicion[J]. Int J Infect Dis, 2014, 23: 69-74. DOI: 10.1016/j.ijid.2013.12.014.
[88]	SPERNOVASILIS N, KOFTERIDIS DP. Pre-existing liver disease and toxicity of antifungals[J]. J Fungi (Basel), 2018, 4(4): 133. DOI: 10.3390/jof4040133.
[89]	BLUMBERG HM, BURMAN WJ, CHAISSON RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of tuberculosis[J]. Am J Respir Crit Care Med, 2003, 167(4): 603-662. DOI: 10.1164/rccm.167.4.603.
[90]	SANAI FM, BZEIZI KI. Systematic review: Tuberculous peritonitis--presenting features, diagnostic strategies and treatment[J]. Aliment Pharmacol Ther, 2005, 22(8): 685-700. DOI: 10.1111/j.1365-2036.2005.02645.x.
[91]	SAIGAL S, AGARWAL SR, NANDEESH HP, et al. Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: A preliminary report[J]. J Gastroenterol Hepatol, 2001, 16(9): 1028-1032. DOI: 10.1046/j.1440-1746.2001.02570.x.
[92]	SARTELLI M, VIALE P, CATENA F, et al. 2013 WSES guidelines for management of intra-abdominal infections[J]. World J Emerg Surg, 2013, 8(1): 3. DOI: 10.1186/1749-7922-8-3.
[93]	LIANG WC, ZHU YC, HA FL, et al. Distribution of pathogenic bacteria in bile of patients with biliary tract infection and change of sensitivity to drugs[J]. Jilin Med J, 2018, 39(2): 301-303. DOI: 10.3969/j.issn.1004-0412.2018.02.045. 梁伟潮, 朱应昌, 韩福郎, 等. 胆道感染患者胆汁中病原菌的分布及对药物的敏感性变化分析[J]. 吉林医学, 2018, 39(2): 301-303. DOI: 10.3969/j.issn.1004-0412.2018.02.045.
[94]	ZHANG GQ, YAO YH, XU QP, et al. Analysis on the distribution and drug resistance of biliary tract infection microorganism[J]. Exp Lab Med, 2008, 26(5): 551-552, 547. DOI: 10.3969/j.issn.1674-1129.2008.05.039. 张国强, 姚艺辉, 许奇萍, 等. 胆道感染微生物分布及菌株耐药性分析[J]. 实验与检验医学, 2008, 26(5): 551-552, 547. DOI: 10.3969/j.issn.1674-1129.2008.05.039.
[95]	LUBBERT C, MUTTERS R. Gastrointestinal infections[J]. Internist (Berl), 2017, 58(2): 149-169. DOI: 10.1007/s00108-016-0183-y.
[96]	PRINA E, RANZANI OT, TORRES A. Community-acquired pneumonia[J]. Lancet, 2015, 386(9998): 1097-1108. DOI: 10.1016/S0140-6736(15)60733-4.
[97]	KALIL AC, METERSKY ML, KLOMPAS M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society[J]. Clin Infect Dis, 2016, 63(5): e61-e111. DOI: 10.1093/cid/ciw353.
[98]	KLEIN RD, HULTGREN SJ. Urinary tract infections: Microbial pathogenesis, host-pathogen interactions and new treatment strategies[J]. Nat Rev Microbiol, 2020, 18(4): 211-226. DOI: 10.1038/s41579-020-0324-0.
[99]	BARTOLETTI M, GIANNELLA M, LEWIS RE, et al. Extended infusion of β-lactams for bloodstream infection in patients with liver cirrhosis: An observational multicenter study[J]. Clin Infect Dis, 2019, 69(10): 1731-1739. DOI: 10.1093/cid/ciz032.
[100]	DONG Y, LI Y, ZHANG Y, et al. Clinical efficacy and cost-effectiveness of β-lactam/β-lactamase inhibitor combinations and carbapenems in liver cirrhosis patients with gram-negative bacteria bloodstream infection[J]. Infect Drug Resist, 2020, 13: 1327-1338. DOI: 10.2147/IDR.S241648.
[101]	SOOD A, MIDHA V, GOYAL O, et al. Skin and soft tissue infections in cirrhotics: A prospective analysis of clinical presentation and factors affecting outcome[J]. Indian J Gastroenterol, 2014, 33(3): 281-284. DOI: 10.1007/s12664-014-0454-2.
[102]	STEVENS DL, BISNO AL, CHAMBERS HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America[J]. Clin Infect Dis, 2014, 59(2): e10-e52. DOI: 10.1093/cid/ciu444.
[103]	HE LX, XIAO YH, LU Q, et al. National Guidelines for antimicrobial therapy[M]. Beijing: People's Medical Publishing House, 2012: 311. ISBN: 978-7-117-16223-4. 何礼贤, 肖永红, 陆权, 等. 国家抗微生物指南[M]. 北京: 人民卫生出版社; 2012: 311. ISBN: 978-7-117-16223-4.
[104]	WONG-BERINGER A, KRIENGKAUYKIAT J. Systemic antifungal therapy: New options, new challenges[J]. Pharmacotherapy, 2003, 23(11): 1441-1462. DOI: 10.1592/phco.23.14.1441.31938.
[105]	VICTOR DW 3rd, QUIGLEY EM. Microbial therapy in liver disease: Probiotics probe the microbiome-gut-liver-brain axis[J]. Gastroenterology, 2014, 147(6): 1216-1218. DOI: 10.1053/j.gastro.2014.10.023.
[106]	DENG TZ, HAN XY, ZHANG J, et al. Effect of probiotics on gut microflora, immune function and inflammatory response in patients with chronic liver failure[J]. J Pathog Biol, 2018, 13(4): 408-412. DOI: 10.13350/j.cjpb.180419. 邓桃枝, 韩向阳, 张洁, 等. 微生态制剂对慢性肝衰竭患者肠道微生态、免疫功能及炎症反应的影响[J]. 中国病原生物学杂志, 2018, 13(4): 408-412. DOI: 10.13350/j.cjpb.180419.
[107]	SORIANO G, GUARNER C, TEIXIDÓ M, et al. Selective intestinal decontamination prevents spontaneous bacterial peritonitis[J]. Gastroenterology, 1991, 100(2): 477-481. DOI: 10.1016/0016-5085(91)90219-b.
[108]	SUCH J, GUARNER C, SORIANO G, et al. Selective intestinal decontamination increases serum and ascitic fluid C3 levels in cirrhosis[J]. Hepatology, 1990, 12(5): 1175-1178. DOI: 10.1002/hep.1840120516.
[109]	EL AGGAN HA, EL-AGGAN HA, ABOU SEIF HELMY M, et al. Selective intestinal decontamination in patients with schistosomal hepatic fibrosis and low-protein ascites[J]. J Egypt Soc Parasitol, 1993, 23(3): 649-657.
[110]	OLIVER A, WONG M, SANCHEZ C. Role of rifaximin in spontaneous bacterial peritonitis prevention[J]. South Med J, 2018, 111(11): 660-665. DOI: 10.14423/SMJ.0000000000000887.
[111]	MENSHAWY A, MATTAR O, BARSSOUM K, et al. Safety and efficacy of rifaximin in prophylaxis of spontaneous bacterial peritonitis: A systematic review and meta-analysis[J]. Curr Drug Targets, 2019, 20(4): 380-387. DOI: 10.2174/1389450119666180924145156.
[112]	ELFERT A, ABO ALI L, SOLIMAN S, et al. Randomized-controlled trial of rifaximin versus norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis[J]. Eur J Gastroenterol Hepatol, 2016, 28(12): 1450-1454. DOI: 10.1097/MEG.0000000000000724.
[113]	LI P, LIANG X, XU S, et al. A non-bioartificial liver support system combined with transplantation in HBV-related acute-on-chronic liver failure[J]. Sci Rep, 2021, 11(1): 2975. DOI: 10.1038/s41598-021-82719-x.
[114]	National Clinical Research Center for Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases. Expert consensus on the application of artificial liver blood purification system in the treatment of severe and critical COVID-19[J]. J Clin Hepatol, 2020, 36(6): 1228-1229. DOI: 10.3969/j.issn.1001-5256.2020.06.008. 国家感染性疾病临床医学研究中心, 传染病诊治国家重点实验室. 人工肝血液净化系统应用于重型、危重型新型冠状病毒肺炎治疗的专家共识[J]. 临床肝胆病杂志, 2020, 36(6): 1228-1229. DOI: 10.3969/j.issn.1001-5256.2020.06.008.
[115]	ZHOU J, WANG XX, LIAN JS, et al. Comparison of efficacy and safety between artificial liver plasma dia-filtration (PDF) and plasma exchange with continuous veno-venous hemofiltration (FPE+CVVH) for mid and late stage liver failure[J]. Chin J Clin Infect Dis, 2018, 11(5): 369-373. DOI: 10.3760/cma.j.issn.1674-2397.2018.05.008. 周健, 王笑笑, 连江山, 等. 人工肝血浆透析滤过与选择性血浆置换联合连续性血液滤过治疗中晚期肝衰竭疗效及安全性比较[J]. 中华临床感染病杂志, 2018, 11(5): 369-373. DOI: 10.3760/cma.j.issn.1674-2397.2018.05.008.
[116]	CHENG YW, ALHAFFAR D, SAHA S, et al. Fecal microbiota transplantation is safe and effective in patients with clostridioides difficile infection and cirrhosis[J]. Clin Gastroenterol Hepatol, 2021, 19(8): 1627-1634. DOI: 10.1016/j.cgh.2020.06.051.
[117]	LIU H, ZHANG Q, LIU L, et al. Effect of artificial liver support system on short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure[J]. Artif Organs, 2020, 44(10): E434-E447. DOI: 10.1111/aor.13710.
[118]	LARSEN FS. Artificial liver support in acute and acute-on-chronic liver failure[J]. Curr Opin Crit Care, 2019, 25(2): 187-191. DOI: 10.1097/MCC.0000000000000584.
[119]	GARCÍA MARTÍNEZ JJ, BENDJELID K. Artificial liver support systems: What is new over the last decade?[J]. Ann Intensive Care, 2018, 8(1): 109. DOI: 10.1186/s13613-018-0453-z.
[120]	MA K, GUO W, HAN M, et al. Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure: Establishment of a novel logistical regression model[J]. Hepatol Int, 2012, 6(4): 735-743. DOI: 10.1007/s12072-012-9344-9.
[121]	WANG J, MA K, HAN M, et al. Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: Validation of the TPPM model[J]. Hepatol Int, 2014, 8(1): 64-71. DOI: 10.1007/s12072-013-9485-5.
[122]	HABIB S, YARLAGADDA S, CARREON TA, et al. Fungal infection in acutely decompensated cirrhosis patients: Value of model for end-stage liver disease score[J]. Gastroenterology Res, 2020, 13(5): 199-207. DOI: 10.14740/gr1255.
[123]	HUNG CC, HSU YC, LIN KH. Comparing mortality risk predictive ability of different scoring systems in cirrhotic patients with bacteremia[J]. Emerg Med Int, 2020, 2020: 8596567. DOI: 10.1155/2020/8596567.
[124]	PIANO S, BARTOLETTI M, TONON M, et al. Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections[J]. Gut, 2018, 67(10): 1892-1899. DOI: 10.1136/gutjnl-2017-314324.
[125]	LIN KH, WANG FL, WU MS, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection in patients with liver cirrhosis: A systematic review and meta-analysis[J]. Diagn Microbiol Infect Dis, 2014, 80(1): 72-78. DOI: 10.1016/j.diagmicrobio.2014.03.029.
[126]	ZHANG Z, YANG Z, CHENG Q, et al. Establishment and validation of a prognostic model for hepatitis B virus-related acute-on-chronic liver failure patients with bacterial infection[J]. Hepatol Int, 2022, 16(1): 38-47. DOI: 10.1007/s12072-021-10268-6.
[127]	MERLI M, APRILE F. The European Association for the Study of Liver (EASL) nutrition guidelines[J]. Recenti Prog Med, 2021, 112(2): 103-109. DOI: 10.1701/3559.35370.
[128]	PIOTROWSKI D, SĄCZEWSKA-PIOTROWSKA A, JAROSZEWICZ J, et al. Lymphocyte-to-monocyte ratio as the best simple predictor of bacterial infection in patients with liver cirrhosis[J]. Int J Environ Res Public Health, 2020, 17(5): 1727. DOI: 10.3390/ijerph17051727.
[129]	YANG Q, JIANG XZ, ZHU YF, et al. Clinical risk factors and predictive tool of bacteremia in patients with cirrhosis[J]. J Int Med Res, 2020, 48(5): 300060520919220. DOI: 10.1177/0300060520919220.
[130]	ZHANG Z, MA K, YANG Z, et al. Development and validation of a clinical predictive model for bacterial infection in hepatitis B virus-related acute-on-chronic liver failure[J]. Infect Dis Ther, 2021, 10(3): 1347-1361. DOI: 10.1007/s40121-021-00454-2.