提示: 手机请竖屏浏览!

肝硬化患者感染带来的不断演变的挑战
The Evolving Challenge of Infections in Cirrhosis


Jasmohan S. Bajaj ... 传染病 • 2021.06.17
相关阅读
• 腹腔积液、自发性细菌性腹膜炎和肝肾综合征的治疗 • 慢性肝炎的全球消除 • 肝细胞癌 • 非酒精性脂肪性肝炎的病因、发病机制和治疗

肝硬化患者感染是巨大且不断增加的健康和经济负担1。约2/3的肝硬化合并肝外器官衰竭患者有脓毒症1。这些患者与无肝硬化的脓毒症患者相比,住院时间长达2倍,费用接近3倍,且院内死亡率超过50% 1。感染使肝硬化患者的死亡风险增加3倍,且死亡风险与衰竭器官数量对应2,3。感染SARS-CoV-2的肝硬化患者的死亡率也很高4

在一项关于肝硬化患者感染的全球性研究中,48%的感染为社区获得性,26%与医疗相关(即入院后48小时内做出诊断),26%为院内感染(即入院48小时后做出诊断)5。一般而言,医疗相关感染的定义为发生于接触医疗系统的患者,但不能归类为医院获得性,也不能归类为社区获得性的感染。只有59%患者的细菌培养结果呈阳性;最常见的感染是自发性细菌性腹膜炎(27%),其次是尿路感染和肺炎5。在北美洲近期的一项研究中,院内感染发生于15%的肝硬化住院患者,且与死亡风险增加相关6。其中约有一半患者的院内感染是在因其他感染接受治疗后发生。令人关注的主要问题是多药耐药(MDR)微生物感染的患病率不断上升。MDR感染在亚洲最为高发,尤其是印度;印度的肝硬化患者感染中,70%是由MDR微生物引起的5。肝硬化患者的感染患病率不断上升,而预防、早期发现和治疗策略的制定一直面临挑战。





作者信息

Jasmohan S. Bajaj, M.D., Patrick S. Kamath, M.D., and K. Rajender Reddy, M.D.
From Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond (J.S.B.); Mayo Clinic College of Medicine and Science, Rochester, MN (P.S.K.); and the University of Pennsylvania, Philadelphia (K.R.R.). Address reprint requests to Dr. Reddy at the University of Pennsylvania, 2 Dulles, 3400 Spruce St., Philadelphia, PA 19104, or at reddyr@pennmedicine.upenn.edu.

 

参考文献

1. Allen AM, Kim WR, Moriarty JP, Shah ND, Larson JJ, Kamath PS. Time trends in the health care burden and mortality of acute on chronic liver failure in the United States. Hepatology 2016;64:2165-2172.

2. Bajaj JS, O’Leary JG, Reddy KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 2014;60:250-256.

3. 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. Gastroenterology 2010;139(4):1246-1256.

4. Bajaj JS, Garcia-Tsao G, Biggins SW, et al. Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort. Gut 2020;70:531-536.

5. Piano S, Singh V, Caraceni P, et al. Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide. Gastroenterology 2019;156(5):1368.e10-1380.e10.

6. Bajaj JS, OʼLeary JG, Tandon P, et al. Nosocomial infections are frequent and negatively impact outcomes in hospitalized patients with cirrhosis. Am J Gastroenterol 2019;114:1091-1100.

7. Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2011;9:727-738.

8. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014;61:1385-1396.

9. O’Leary JG, Reddy KR, Wong F, et al. Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2015;13(4):753.e1-759.e1.

10. Fernández J, Acevedo J, Wiest R, et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut 2018;67:1870-1880.

11. Wiest R, Albillos A, Trauner M, Bajaj JS, Jalan R. Targeting the gut-liver axis in liver disease. J Hepatol 2017;67:1084-1103.

12. Bajaj JS, Heuman DM, Hylemon PB, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol 2014;60:940-947.

13. Bajaj JS, Reddy RK, Tandon P, et al. Prediction of fungal infection development and their impact on survival using the NACSELD cohort. Am J Gastroenterol 2018;113:556-563.

14. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. Int J Infect Dis 2007;11:482-487.

15. Pieri G, Agarwal B, Burroughs AK. C-reactive protein and bacterial infection in cirrhosis. Ann Gastroenterol 2014;27:113-120.

16. Runyon BA, AASLD. Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology 2013;57:1651-1653.

17. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites and hepatorenal syndrome. Hepatology 2021 May 03 (Epub ahead of print).

18. Fernández J, Bert F, Nicolas-Chanoine M-H. The challenges of multi-drug-resistance in hepatology. J Hepatol 2016;65:1043-1054.

19. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018;69:406-460.

20. Evans LT, Kim WR, Poterucha JJ, Kamath PS. Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites. Hepatology 2003;37:897-901.

21. Piano S, Fasolato S, Salinas F, et al. The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: results of a randomized, controlled clinical trial. Hepatology 2016;63:1299-1309.

22. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-409.

23. Fernández J, Acevedo J, Prado V, et al. Clinical course and short-term mortality of cirrhotic patients with infections other than spontaneous bacterial peritonitis. Liver Int 2017;37:385-395.

24. Bajaj JS, Ananthakrishnan AN, Hafeezullah M, et al. Clostridium difficile is associated with poor outcomes in patients with cirrhosis: a national and tertiary center perspective. Am J Gastroenterol 2010;105:106-113.

25. Thulstrup AM, Mølle I, Svendsen N, Sørensen HT. Incidence and prognosis of tuberculosis in patients with cirrhosis of the liver: a Danish nationwide population based study. Epidemiol Infect 2000;124:221-225.

26. Alexopoulou A, Vasilieva L, Agiasotelli D, Dourakis SP. Fungal infections in patients with cirrhosis. J Hepatol 2015;63:1043-1045.

27. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62(4):e1-e50.

28. Fernández J, Tandon P, Mensa J, Garcia-Tsao G. Antibiotic prophylaxis in cirrhosis: good and bad. Hepatology 2016;63:2019-2031.

29. Fernández J, Ruiz del Arbol L, Gómez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology 2006;131:1049-1056.

30. Li H, Wieser A, Zhang J, et al. Patients with cirrhosis and SBP: increase in multidrug-resistant organisms and complications. Eur J Clin Invest 2020;50(2):e13198-e13198.

31. Elfert A, Abo Ali L, Soliman S, Ibrahim S, Abd-Elsalam S. Randomized-controlled trial of rifaximin versus norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol 2016;28:1450-1454.

32.Salehi S, Tranah TH, Lim S, et al. Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all-cause admissions in patients on the liver transplant waiting list. Aliment Pharmacol Ther 2019;50:435-441.

33. Rimola A, García-Tsao G, Navasa M, et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. J Hepatol 2000;32:142-153.

34. Moreau R, Elkrief L, Bureau C, et al. Effects of long-term norfloxacin therapy in patients with advanced cirrhosis. Gastroenterology 2018;155(6):1816.e9-1827.e9.

35. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014;60:1310-1324.

36. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites and hepatorenal syndrome. Hepatology (in press).

37. Fernández J, Acevedo J, Castro M, et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology 2012;55:1551-1561.

38. Cruz RCR, Tanajura D, Almeida D, Cruz M, Paraná R. Urinary tract infection in non-hospitalized patients with cirrhosis and no symptoms of urinary tract infection: a case series study. Braz J Infect Dis 2006;10:380-383.

39. Evans JDW, Morris PJ, Knight SR. Antifungal prophylaxis in liver transplantation: a systematic review and network meta-analysis. Am J Transplant 2014;14:2765-2776.

40. Ariza X, Castellote J, Lora-Tamayo J, et al. Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis. J Hepatol 2012;56:825-832.

41. Karvellas CJ, Abraldes JG, Arabi YM, Kumar A. Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study. Aliment Pharmacol Ther 2015;41:747-757.

42. Arroyo V, Moreau R, Jalan R. Acute-on-chronic liver failure. N Engl J Med 2020;382:2137-2145.

43. Izzy M, VanWagner LB, Lin G, et al. Redefining cirrhotic cardiomyopathy for the modern era. Hepatology 2020;71:334-345.

44. Galbois A, Aegerter P, Martel-Samb P, et al. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study. Crit Care Med 2014;42:1666-1675.

45. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-810.

46. Nadim MK, Durand F, Kellum JA, et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol 2016;64:717-735.

47. Simonetto DA, Piccolo Serafim L, Gallo de Moraes A, Gajic O, Kamath PS. Management of sepsis in patients with cirrhosis: current evidence and practical approach. Hepatology 2019;70:418-428.

48. Galbois A, Bigé N, Pichereau C, et al. Exploration of skin perfusion in cirrhotic patients with septic shock. J Hepatol 2015;62:549-555.

49. O’Brien AJ, Fullerton JN, Massey KA, et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med 2014;20:518-523.

50. Xu J-Y, Chen Q-H, Xie J-F, et al. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials. Crit Care 2014;18:702-702.

51. Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med 2021;384:818-828.

52. Fernández J, Escorsell A, Zabalza M, et al. Adrenal insufficiency in patients with cirrhosis and septic shock: effect of treatment with hydrocortisone on survival. Hepatology 2006;44:1288-1295.

53. Arabi YM, Aljumah A, Dabbagh O, et al. Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial. CMAJ 2010;182:1971-1977.

54. O’Leary JG, Reddy KR, Garcia-Tsao G, et al. NACSELD acute-on-chronic liver failure (NACSELD-ACLF) score predicts 30-day survival in hospitalized patients with cirrhosis. Hepatology 2018;67:2367-2374.

55. Jalan R, Saliba F, Pavesi M, et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014;61:1038-1047.

56. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2020;384:403-416.

57. Fix OK, Blumberg EA, Chang K-M, et al. AASLD expert panel consensus statement: vaccines to prevent COVID-19 infection in patients with liver disease. American Association for the Study of Liver Diseases. February 2, 2021 (https://www.aasld.org/sites/default/files/2021-02/AASLD-COVID19-VaccineDocument-February2021-FINAL.pdf.).

58. Cao MD, Ganesamoorthy D, Elliott AG, Zhang H, Cooper MA, Coin LJM. Streaming algorithms for identification of pathogens and antibiotic resistance potential from real-time MinION sequencing. Gigascience 2016;5:32-32.

59. Bajaj JS, Vargas HE, Reddy KR, et al. Association between intestinal microbiota collected at hospital admission and outcomes of patients with cirrhosis. Clin Gastroenterol Hepatol 2019;17(4):756.e3-765.e3.

60. Watts GS, Thornton JE Jr, Youens-Clark K, et al. Identification and quantitation of clinically relevant microbes in patient samples: comparison of three k-mer based classifiers for speed, accuracy, and sensitivity. PLoS Comput Biol 2019;15(11):e1006863-e1006863.

61. Caraceni P, Riggio O, Angeli P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet 2018;391:2417-2429.

62. Solà E, Solé C, Simón-Talero M, et al. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation: a randomized placebo-controlled trial. J Hepatol 2018;69:1250-1259.

63. China L, Freemantle N, Forrest E, et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med 2021;384:808-817.

64. Mullineaux-Sanders C, Suez J, Elinav E, Frankel G. Sieving through gut models of colonization resistance. Nat Microbiol 2018;3:132-140.

65. Libertucci J, Young VB. The role of the microbiota in infectious diseases. Nat Microbiol 2019;4:35-45.

66. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014;60:715-735.

67. Allegretti JR, Mullish BH, Kelly C, Fischer M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet 2019;394:420-431.

68. Manges AR, Steiner TS, Wright AJ. Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review. Infect Dis (Lond) 2016;48:587-592.

69. Bajaj JS, Kassam Z, Fagan A, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology 2017;66:1727-1738.

70. Bajaj JS, Shamsaddini A, Fagan A, et al. Fecal microbiota transplant in cirrhosis reduces gut microbial antibiotic resistance genes: analysis of two trials. Hepatol Commun 2020;5:258-271.

71. DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med 2019;381:2043-2050.

72. Crofts TS, Gasparrini AJ, Dantas G. Next-generation approaches to understand and combat the antibiotic resistome. Nat Rev Microbiol 2017;15:422-434.

73. Kutter E, De Vos D, Gvasalia G, et al. Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol 2010;11:69-86.

服务条款 | 隐私政策 | 联系我们