Semin Liver Dis 2023; 43(01): 117-132
DOI: 10.1055/a-2015-1290
Review Article

Cirrhosis Management in the Intensive Care Unit

Thomas N. Smith
1   Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota
Alice Gallo de Moraes
2   Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, Minnesota
Douglas A. Simonetto
3   Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
› Author Affiliations
Funding None.


Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.

Publication History

Accepted Manuscript online:
18 January 2023

Article published online:
13 February 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study. BMJ 2018; 362: k2817
  • 2 Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol 2020; 18 (12) 2650-2666
  • 3 Scaglione S, Kliethermes S, Cao G. et al. The epidemiology of cirrhosis in the United States: a population-based study. J Clin Gastroenterol 2015; 49 (08) 690-696
  • 4 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 (06) 2165-2172
  • 5 Olson JC, Wendon JA, Kramer DJ. et al. Intensive care of the patient with cirrhosis. Hepatology 2011; 54 (05) 1864-1872
  • 6 Majumdar A, Bailey M, Kemp WM, Bellomo R, Roberts SK, Pilcher D. Declining mortality in critically ill patients with cirrhosis in Australia and New Zealand between 2000 and 2015. J Hepatol 2017; 67 (06) 1185-1193
  • 7 Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet 2021; 398 10308 1359-1376
  • 8 D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44 (01) 217-231
  • 9 Trebicka J, Fernandez J, Papp M. et al; PREDICT STUDY Group of the EASL-CLIF Consortium.. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J Hepatol 2020; 73 (04) 842-854
  • 10 Sarin SK, Choudhury A, Sharma MK. et al; APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party.. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019; 13 (04) 353-390
  • 11 Jalan R, Saliba F, Pavesi M. et al; CANONIC Study Investigators of the EASL-CLIF Consortium. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014; 61 (05) 1038-1047
  • 12 Bajaj JS, O'Leary JG, Reddy KR. et al; North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 2014; 60 (01) 250-256
  • 13 Hernaez R, Solà E, Moreau R, Ginès P. Acute-on-chronic liver failure: an update. Gut 2017; 66 (03) 541-553
  • 14 Trebicka J, Fernandez J, Papp M. et al; PREDICT STUDY Group of the EASL-CLIF CONSORTIUM. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. J Hepatol 2021; 74 (05) 1097-1108
  • 15 Arroyo V, Moreau R, Jalan R. Acute-on-chronic liver failure. N Engl J Med 2020; 382 (22) 2137-2145
  • 16 Moreau R, Jalan R, Gines P. et al; CANONIC Study Investigators of the EASL–CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144 (07) 1426-1437 , 1437.e1–1437.e9
  • 17 Siewers K, Abdullah SMOB, Sørensen RH, Nielsen FE. Time to administration of antibiotics and mortality in sepsis. J Am Coll Emerg Physicians Open 2021; 2 (03) e12435
  • 18 Liu VX, Fielding-Singh V, Greene JD. et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017; 196 (07) 856-863
  • 19 Emerson P, McPeake J, O'Neill A. et al. The utility of scoring systems in critically ill cirrhotic patients admitted to a general intensive care unit. J Crit Care 2014; 29 (06) 1131.e1-1131.e6
  • 20 Theocharidou E, Pieri G, Mohammad AO. et al. The Royal Free Hospital score: a calibrated prognostic model for patients with cirrhosis admitted to intensive care unit. Comparison with current models and CLIF-SOFA score. Am J Gastroenterol 2014; 109 (04) 554-562
  • 21 Jalan R, Gines P, Olson JC. et al. Acute-on chronic liver failure. J Hepatol 2012; 57 (06) 1336-1348
  • 22 Piano S, Bartoletti M, Tonon M. et al. Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections. Gut 2018; 67 (10) 1892-1899
  • 23 Patidar KR, Shaw J, Acharya C. et al. No association between Quick Sequential Organ Failure Assessment and outcomes of patients with cirrhosis and infections. Clin Gastroenterol Hepatol 2017; 15 (11) 1803-1804
  • 24 Son J, Choi S, Huh JW. et al. The quick sepsis-related organ failure score has limited value for predicting adverse outcomes in sepsis patients with liver cirrhosis. Korean J Intern Med (Korean Assoc Intern Med) 2020; 35 (04) 861-872
  • 25 Müller M, Schefold JC, Leichtle AB. et al. qSOFA score not predictive of in-hospital mortality in emergency patients with decompensated liver cirrhosis. Med Klin Intensivmed Notf Med 2019; 114 (08) 724-732
  • 26 Choi C, Choi DH, Spears GM. et al. Relationship between etiology of cirrhosis and survival among patients hospitalized in intensive care units. Mayo Clin Proc 2022; 97 (02) 274-284
  • 27 Kim JH, Jun BG, Lee M. et al. Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: a multicenter study. Clin Mol Hepatol 2022; 28 (03) 540-552
  • 28 Peng Y, Qi X, Guo X. Child-Pugh versus MELD score for the assessment of prognosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Medicine (Baltimore) 2016; 95 (08) e2877
  • 29 Levesque E, Hoti E, Azoulay D. et al. Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit. J Hepatol 2012; 56 (01) 95-102
  • 30 O'Brien AJ, Welch CA, Singer M, Harrison DA. Prevalence and outcome of cirrhosis patients admitted to UK intensive care: a comparison against dialysis-dependent chronic renal failure patients. Intensive Care Med 2012; 38 (06) 991-1000
  • 31 Das V, Boelle PY, Galbois A. et al. Cirrhotic patients in the medical intensive care unit: early prognosis and long-term survival. Crit Care Med 2010; 38 (11) 2108-2116
  • 32 Olson JC, Karvellas CJ. Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit. Liver Transpl 2017; 23 (11) 1465-1476
  • 33 Bajaj JS, O'Leary JG, Lai JC. et al. Acute-on-chronic liver failure clinical guidelines. Am J Gastroenterol 2022; 117 (02) 225-252
  • 34 European Association for the Study of the Liver. Electronic address:; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 2022; 77 (03) 807-824
  • 35 Drolz A, Jäger B, Wewalka M. et al. Clinical impact of arterial ammonia levels in ICU patients with different liver diseases. Intensive Care Med 2013; 39 (07) 1227-1237
  • 36 Mehtani R, Garg S, Kajal K, Soni SL, Premkumar M. Neurological monitoring and sedation protocols in the liver intensive care unit. Metab Brain Dis 2022; 37 (05) 1291-1307
  • 37 Sharma BC, Sharma P, Lunia MK, Srivastava S, Goyal R, Sarin SK. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol 2013; 108 (09) 1458-1463
  • 38 Rose CF, Amodio P, Bajaj JS. et al. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol 2020; 73 (06) 1526-1547
  • 39 Sharma BC, Sharma P, Agrawal A, Sarin SK. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology 2009; 137 (03) 885-891, 891.e1
  • 40 Agrawal A, Sharma BC, Sharma P, Sarin SK. Secondary prophylaxis of hepatic encephalopathy in cirrhosis: an open-label, randomized controlled trial of lactulose, probiotics, and no therapy. Am J Gastroenterol 2012; 107 (07) 1043-1050
  • 41 Kimer N, Krag A, Møller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther 2014; 40 (02) 123-132
  • 42 Bass NM, Mullen KD, Sanyal A. et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362 (12) 1071-1081
  • 43 Treggiari MM, Romand JA, Yanez ND. et al. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med 2009; 37 (09) 2527-2534
  • 44 McKeage K, Perry CM. Propofol: a review of its use in intensive care sedation of adults. CNS Drugs 2003; 17 (04) 235-272
  • 45 Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342 (20) 1471-1477
  • 46 Nadim MK, Durand F, Kellum JA. et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol 2016; 64 (03) 717-735
  • 47 Guerit JM, Amantini A, Fischer C. et al; Members of the ISHEN Commission on Neurophysiological Investigations. Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 2009; 29 (06) 789-796
  • 48 Ginès P, Schrier RW. Renal failure in cirrhosis. N Engl J Med 2009; 361 (13) 1279-1290
  • 49 Chayanupatkul M, Liangpunsakul S. Cirrhotic cardiomyopathy: review of pathophysiology and treatment. Hepatol Int 2014; 8 (03) 308-315
  • 50 Malbrain ML, De Waele JJ, De Keulenaer BL. What every ICU clinician needs to know about the cardiovascular effects caused by abdominal hypertension. Anaesthesiol Intensive Ther 2015; 47 (04) 388-399
  • 51 Aspesi M, Gamberoni C, Severgnini P. et al. The abdominal compartment syndrome. Clinical relevance. Minerva Anestesiol 2002; 68 (04) 138-146
  • 52 Nanchal R, Subramanian R, Karvellas CJ. et al. Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU: cardiovascular, endocrine, hematologic, pulmonary, and renal considerations. Crit Care Med 2020; 48 (03) e173-e191
  • 53 Humphrey H, Hall J, Sznajder I, Silverstein M, Wood L. Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest 1990; 97 (05) 1176-1180
  • 54 Rosenberg AL, Dechert RE, Park PK, Bartlett RH. NIH NHLBI ARDS Network. Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort. J Intensive Care Med 2009; 24 (01) 35-46
  • 55 Brandstrup B, Tønnesen H, Beier-Holgersen R. et al; Danish Study Group on Perioperative Fluid Therapy. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003; 238 (05) 641-648
  • 56 Wiedemann HP, Wheeler AP, Bernard GR. et al; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354 (24) 2564-2575
  • 57 Rhodes A, Cusack RJ, Newman PJ, Grounds RM, Bennett ED. A randomised, controlled trial of the pulmonary artery catheter in critically ill patients. Intensive Care Med 2002; 28 (03) 256-264
  • 58 De Backer D, Fagnoul D. Intensive care ultrasound: VI. Fluid responsiveness and shock assessment. Ann Am Thorac Soc 2014; 11 (01) 129-136
  • 59 Levitov A, Frankel HL, Blaivas M. et al. Guidelines for the appropriate use of bedside general and cardiac ultrasonography in the evaluation of critically ill patients - Part II: Cardiac ultrasonography. Crit Care Med 2016; 44 (06) 1206-1227
  • 60 Via G, Tavazzi G, Price S. Ten situations where inferior vena cava ultrasound may fail to accurately predict fluid responsiveness: a physiologically based point of view. Intensive Care Med 2016; 42 (07) 1164-1167
  • 61 Porter TR, Shillcutt SK, Adams MS. et al. Guidelines for the use of echocardiography as a monitor for therapeutic intervention in adults: a report from the American Society of Echocardiography. J Am Soc Echocardiogr 2015; 28 (01) 40-56
  • 62 Rowan KM, Angus DC, Bailey M. et al; PRISM Investigators. Early, goal-directed therapy for septic shock - a patient-level meta-analysis. N Engl J Med 2017; 376 (23) 2223-2234
  • 63 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 (01) 418-428
  • 64 Casserly B, Phillips GS, Schorr C. et al. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 2015; 43 (03) 567-573
  • 65 Lee SM, An WS. New clinical criteria for septic shock: serum lactate level as new emerging vital sign. J Thorac Dis 2016; 8 (07) 1388-1390
  • 66 Ryoo SM, Lee J, Lee YS. et al. Lactate level versus lactate clearance for predicting mortality in patients with septic shock defined by Sepsis-3. Crit Care Med 2018; 46 (06) e489 –e495
  • 67 Funk GC, Doberer D, Kneidinger N, Lindner G, Holzinger U, Schneeweiss B. Acid-base disturbances in critically ill patients with cirrhosis. Liver Int 2007; 27 (07) 901-909
  • 68 Annane D, Siami S, Jaber S. et al; CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA 2013; 310 (17) 1809-1817
  • 69 Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350 (22) 2247-2256
  • 70 Caironi P, Tognoni G, Masson S. et al; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370 (15) 1412-1421
  • 71 Dellinger RP, Levy MM, Carlet JM. et al; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society European Society of Clinical Microbiology and Infectious Diseases;European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36 (01) 296-327
  • 72 Rochwerg B, Alhazzani W, Sindi A. et al; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med 2014; 161 (05) 347-355
  • 73 Zou Y, Ma K, Xiong JB, Xi CH, Deng XJ. Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis. Sao Paulo Med J 2018; 136 (05) 421-432
  • 74 Philips CA, Maiwall R, Sharma MK. et al. Comparison of 5% human albumin and normal saline for fluid resuscitation in sepsis induced hypotension among patients with cirrhosis (FRISC study): a randomized controlled trial. Hepatol Int 2021; 15 (04) 983-994
  • 75 Maiwall R, Kumar A, Pasupuleti SSR. et al. A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]. J Hepatol 2022; 77 (03) 670-682
  • 76 Thévenot T, Bureau C, Oberti F. et al. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J Hepatol 2015; 62 (04) 822-830
  • 77 Guevara M, Terra C, Nazar A. et al. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol 2012; 57 (04) 759-765
  • 78 Sauneuf B, Champigneulle B, Soummer A. et al. Increased survival of cirrhotic patients with septic shock. Crit Care 2013; 17 (02) R78
  • 79 Myburgh JA, Finfer S, Bellomo R. et al; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367 (20) 1901-1911
  • 80 Schortgen F, Lacherade JC, Bruneel F. et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357 (9260): 911-916
  • 81 Perner A, Haase N, Guttormsen AB. et al; 6S Trial Group; Scandinavian Critical Care Trials Group. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012; 367 (02) 124-134
  • 82 Fernández J, Monteagudo J, Bargallo X. et al. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology 2005; 42 (03) 627-634
  • 83 Salerno F, Navickis RJ, Wilkes MM. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials. Clin Gastroenterol Hepatol 2013; 11 (02) 123-30 .e1
  • 84 Ortega R, Ginès P, Uriz J. et al. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology 2002; 36 (4, Pt 1): 941-948
  • 85 Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology 2012; 55 (04) 1172-1181
  • 86 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315 (08) 801-810
  • 87 Siddiqui MS, Stravitz RT. Intensive care unit management of patients with liver failure. Clin Liver Dis 2014; 18 (04) 957-978
  • 88 Vincent JL, Biston P, Devriendt J, Brasseur A, De Backer D. Dopamine versus norepinephrine: is one better?. Minerva Anestesiol 2009; 75 (05) 333-337
  • 89 De Backer D, Biston P, Devriendt J. et al; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362 (09) 779-789
  • 90 Avni T, Lador A, Lev S, Leibovici L, Paul M, Grossman A. Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One 2015; 10 (08) e0129305
  • 91 Wagener G, Bakker J. Vasopressin in cirrhosis and sepsis: physiology and clinical implications. Minerva Anestesiol 2015; 81 (12) 1377-1383
  • 92 Fede G, Spadaro L, Tomaselli T. et al. Adrenocortical dysfunction in liver disease: a systematic review. Hepatology 2012; 55 (04) 1282-1291
  • 93 Piccolo Serafim L, Simonetto DA, Anderson AL. et al. Clinical effect of systemic steroids in patients with cirrhosis and septic shock. Shock 2021; 56 (06) 916-920
  • 94 Venkatesh B, Finfer S, Cohen J. et al; ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 2018; 378 (09) 797-808
  • 95 Annane D, Renault A, Brun-Buisson C. et al; CRICS-TRIGGERSEP Network. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med 2018; 378 (09) 809-818
  • 96 Gibbs JT, Louissaint J, Tapper EB. Rate of successful extubation in mechanically ventilated patients with cirrhosis and hepatic coma. Dig Dis Sci 2022; 67 (11) 5336-5344
  • 97 Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342 (18) 1301-1308
  • 98 Plataki M, Hubmayr RD. The physical basis of ventilator-induced lung injury. Expert Rev Respir Med 2010; 4 (03) 373-385
  • 99 Waller EA, Aduen JF, Kramer DJ. et al. Safety of percutaneous dilatational tracheostomy with direct bronchoscopic guidance for solid organ allograft recipients. Mayo Clin Proc 2007; 82 (12) 1502-1508
  • 100 Carvalho L, Parise ER. Evaluation of nutritional status of nonhospitalized patients with liver cirrhosis. Arq Gastroenterol 2006; 43 (04) 269-274
  • 101 Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int 2009; 29 (09) 1396-1402
  • 102 Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol 2012; 10 (02) 117-125
  • 103 Tandon P, Raman M, Mourtzakis M, Merli M. A practical approach to nutritional screening and assessment in cirrhosis. Hepatology 2017; 65 (03) 1044-1057
  • 104 McClave SA, Taylor BE, Martindale RG. et al; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016; 40 (02) 159-211
  • 105 Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi). Hepatology 1996; 23 (05) 1041-1046
  • 106 Mendenhall CL, Moritz TE, Roselle GA. et al. A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study. Hepatology 1993; 17 (04) 564-576
  • 107 Cabré E, Rodríguez-Iglesias P, Caballería J. et al. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology 2000; 32 (01) 36-42
  • 108 Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. Cochrane Database Syst Rev 2012; 2012 (05) CD008344
  • 109 Moreno C, Deltenre P, Senterre C. et al. Intensive enteral nutrition is ineffective for patients with severe alcoholic hepatitis treated with corticosteroids. Gastroenterology 2016; 150 (04) 903-10.e8
  • 110 Plauth M, Cabré E, Riggio O. et al; DGEM (German Society for Nutritional Medicine) ESPEN (European Society for Parenteral and Enteral Nutrition). ESPEN guidelines on enteral nutrition: liver disease. Clin Nutr 2006; 25 (02) 285-294
  • 111 Juakiem W, Torres DM, Harrison SA. Nutrition in cirrhosis and chronic liver disease. Clin Liver Dis 2014; 18 (01) 179-190
  • 112 European Association for the Study of the Liver. Electronic address:; European Association for the Study of the Liver. EASL clinical practice guidelines on nutrition in chronic liver disease. J Hepatol 2019; 70 (01) 172-193
  • 113 Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology 2022; 162 (04) 1334-1342
  • 114 Tapper EB, Henderson JB, Parikh ND, Ioannou GN, Lok AS. Incidence of and risk factors for hepatic encephalopathy in a population-based cohort of Americans with cirrhosis. Hepatol Commun 2019; 3 (11) 1510-1519
  • 115 Trikudanathan G, Israel J, Cappa J, O'Sullivan DM. Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients - a systematic review and meta-analysis. Int J Clin Pract 2011; 65 (06) 674-678
  • 116 Bajaj JS, Zadvornova Y, Heuman DM. et al. Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol 2009; 104 (05) 1130-1134
  • 117 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 (01) 106-113
  • 118 Bajaj JS, Ratliff SM, Heuman DM, Lapane KL. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012; 36 (09) 866-874
  • 119 Mahmud N, Serper M, Taddei TH, Kaplan DE. The association between proton pump inhibitor exposure and key liver-related outcomes in patients with cirrhosis: a Veterans Affairs Cohort Study. Gastroenterology 2022; 163 (01) 257-269 .e6
  • 120 Weersink RA, Bouma M, Burger DM. et al. Safe use of proton pump inhibitors in patients with cirrhosis. Br J Clin Pharmacol 2018; 84 (08) 1806-1820
  • 121 Cholongitas E, Senzolo M, Patch D, Shaw S, O'Beirne J, Burroughs AK. Cirrhotics admitted to intensive care unit: the impact of acute renal failure on mortality. Eur J Gastroenterol Hepatol 2009; 21 (07) 744-750
  • 122 du Cheyron D, Bouchet B, Parienti JJ, Ramakers M, Charbonneau P. The attributable mortality of acute renal failure in critically ill patients with liver cirrhosis. Intensive Care Med 2005; 31 (12) 1693-1699
  • 123 Hampel H, Bynum GD, Zamora E, El-Serag HB. Risk factors for the development of renal dysfunction in hospitalized patients with cirrhosis. Am J Gastroenterol 2001; 96 (07) 2206-2210
  • 124 Davenport A, Sheikh MF, Lamb E, Agarwal B, Jalan R. Acute kidney injury in acute-on-chronic liver failure: where does hepatorenal syndrome fit?. Kidney Int 2017; 92 (05) 1058-1070
  • 125 Allegretti AS, Solà E, Ginès P. Clinical application of kidney biomarkers in cirrhosis. Am J Kidney Dis 2020; 76 (05) 710-719
  • 126 Angeli P, Ginès P, Wong F. et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol 2015; 62 (04) 968-974
  • 127 Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology 2008; 48 (06) 2064-2077
  • 128 Facciorusso A, Chandar AK, Murad MH. et al. Comparative efficacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol 2017; 2 (02) 94-102
  • 129 Gaudry S, Hajage D, Schortgen F. et al; AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med 2016; 375 (02) 122-133
  • 130 Zarbock A, Kellum JA, Schmidt C. et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN Randomized Clinical Trial. JAMA 2016; 315 (20) 2190-2199
  • 131 Ginès P, Solà E, Angeli P, Wong F, Nadim MK, Kamath PS. Hepatorenal syndrome. Nat Rev Dis Primers 2018; 4 (01) 23
  • 132 Huelin P, Solà E, Elia C. et al. Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis: a prospective study. Hepatology 2019; 70 (01) 319-333
  • 133 Allegretti AS, Parada XV, Endres P. et al; HRS-HARMONY Study Investigators. Urinary NGAL as a diagnostic and prognostic marker for acute kidney injury in cirrhosis: a prospective study. Clin Transl Gastroenterol 2021; 12 (05) e00359
  • 134 Velez JCQ, Petkovich B, Karakala N, Huggins JT. Point-of-care echocardiography unveils misclassification of acute kidney injury as hepatorenal syndrome. Am J Nephrol 2019; 50 (03) 204-211
  • 135 Del Risco-Zevallos J, Andújar AM, Piñeiro G. et al. Management of acute renal replacement therapy in critically ill cirrhotic patients. Clin Kidney J 2022; 15 (06) 1060-1070
  • 136 Gonwa TA, Wadei HM. The challenges of providing renal replacement therapy in decompensated liver cirrhosis. Blood Purif 2012; 33 1-3 144-148
  • 137 Jones BE, Allegretti AS, Pose E. et al. Renal replacement therapy for acute kidney injury in severe alcohol-associated hepatitis as a bridge to transplant or recovery. Dig Dis Sci 2022; 67 (02) 697-707
  • 138 Bagshaw SM, Wald R, Adhikari NKJ. et al; STARRT-AKI Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group; United Kingdom Critical Care Research Group; Canadian Nephrology Trials Network; Irish Critical Care Trials Group. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med 2020; 383 (03) 240-251
  • 139 Gaudry S, Hajage D, Martin-Lefevre L. et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet 2021; 397 (10281): 1293-1300
  • 140 European Association for the Study of the Liver. Electronic address:; European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69 (02) 406-460
  • 141 Staufer K, Roedl K, Kivaranovic D. et al. Renal replacement therapy in critically ill liver cirrhotic patients-outcome and clinical implications. Liver Int 2017; 37 (06) 843-850
  • 142 Witzke O, Baumann M, Patschan D. et al. Which patients benefit from hemodialysis therapy in hepatorenal syndrome?. J Gastroenterol Hepatol 2004; 19 (12) 1369-1373
  • 143 Wong LP, Blackley MP, Andreoni KA, Chin H, Falk RJ, Klemmer PJ. Survival of liver transplant candidates with acute renal failure receiving renal replacement therapy. Kidney Int 2005; 68 (01) 362-370
  • 144 Zhang W, Bai M, Yu Y. et al. Safety and efficacy of regional citrate anticoagulation for continuous renal replacement therapy in liver failure patients: a systematic review and meta-analysis. Crit Care 2019; 23 (01) 22
  • 145 Klingele M, Stadler T, Fliser D, Speer T, Groesdonk HV, Raddatz A. Long-term continuous renal replacement therapy and anticoagulation with citrate in critically ill patients with severe liver dysfunction. Crit Care 2017; 21 (01) 294
  • 146 European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010; 53 (03) 397-417
  • 147 Angeli P, Wong F, Watson H, Ginès P. CAPPS Investigators. Hyponatremia in cirrhosis: results of a patient population survey. Hepatology 2006; 44 (06) 1535-1542
  • 148 Flores B, Trivedi HD, Robson SC, Bonder A. Hemostasis, bleeding and thrombosis in liver disease. J Transl Sci 2017; 3 (03) 3
  • 149 Blasi A, Calvo A, Prado V. et al. Coagulation failure in patients with acute-on-chronic liver failure and decompensated cirrhosis: beyond the international normalized ratio. Hepatology 2018; 68 (06) 2325-2337
  • 150 O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: coagulation in cirrhosis. Gastroenterology 2019; 157 (01) 34-43 .e1
  • 151 Kor DJ, Gajic O. Blood product transfusion in the critical care setting. Curr Opin Crit Care 2010; 16 (04) 309-316
  • 152 European Association for the Study of the Liver. Electronic address:; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022; 76 (05) 1151-1184
  • 153 Northup PG, Garcia-Pagan JC, Garcia-Tsao G. et al. Vascular liver disorders, portal vein thrombosis, and procedural bleeding in patients with liver disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73 (01) 366-413
  • 154 Villanueva C, Colomo A, Bosch A. et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368 (01) 11-21
  • 155 Tripodi A, Primignani M, Chantarangkul V. et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44 (02) 440-445
  • 156 Caldwell SH, Hoffman M, Lisman T. et al; Coagulation in Liver Disease Group. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006; 44 (04) 1039-1046
  • 157 Seeff LB, Everson GT, Morgan TR. et al; HALT–C Trial Group. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol 2010; 8 (10) 877-883
  • 158 West J, Card TR. Reduced mortality rates following elective percutaneous liver biopsies. Gastroenterology 2010; 139 (04) 1230-1237
  • 159 Moulis G, Bagheri H, Sailler L. et al; French Association of PharmacoVigilance Centers. Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009-2013 French PharmacoVigilance assessment. Eur J Intern Med 2014; 25 (08) 777-780
  • 160 Gunawan B, Runyon B. The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis. Aliment Pharmacol Ther 2006; 23 (01) 115-120
  • 161 Villa E, Cammà C, Marietta M. et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143 (05) 1253-1260.e4
  • 162 Francoz C, Belghiti J, Vilgrain V. et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54 (05) 691-697
  • 163 Intagliata NM, Henry ZH, Shah N, Lisman T, Caldwell SH, Northup PG. Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding. Liver Int 2014; 34 (01) 26-32
  • 164 Barclay SM, Jeffres MN, Nguyen K, Nguyen T. Evaluation of pharmacologic prophylaxis for venous thromboembolism in patients with chronic liver disease. Pharmacotherapy 2013; 33 (04) 375-382
  • 165 Tsai MH, Peng YS, Chen YC. et al. Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. Hepatology 2006; 43 (04) 673-681
  • 166 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 (05) 1288-1295
  • 167 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 (18) 1971-1977
  • 168 Finfer S, Chittock DR, Su SY. et al; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360 (13) 1283-1297
  • 169 Bajaj JS, O'Leary JG, Reddy KR. et al; NACSELD. Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology 2012; 56 (06) 2328-2335
  • 170 Bajaj JS, O'Leary JG, Wong F, Reddy KR, Kamath PS. Bacterial infections in end-stage liver disease: current challenges and future directions. Gut 2012; 61 (08) 1219-1225
  • 171 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 (05) 1551-1561
  • 172 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 (06) 1310-1324
  • 173 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 (04) 556-563
  • 174 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 (04) 1049-1056 , quiz 1285
  • 175 Ginés P, Rimola A, Planas R. et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology 1990; 12 4, Pt 1 716-724
  • 176 Cannon MD, Martin P, Carrion AF. Bacterial infection in patients with cirrhosis: don't get bugged to death. Dig Dis Sci 2020; 65 (01) 31-37
  • 177 Saab S, Hernandez JC, Chi AC, Tong MJ. Oral antibiotic prophylaxis reduces spontaneous bacterial peritonitis occurrence and improves short-term survival in cirrhosis: a meta-analysis. Am J Gastroenterol 2009; 104 (04) 993-1001 , quiz 1002
  • 178 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 (06) 403-409
  • 179 Vergis N, Atkinson SR, Knapp S. et al. In patients with severe alcoholic hepatitis, prednisolone increases susceptibility to infection and infection-related mortality, and is associated with high circulating levels of bacterial DNA. Gastroenterology 2017; 152 (05) 1068-1077.e4
  • 180 Flamm SL. Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence. Therap Adv Gastroenterol 2011; 4 (03) 199-206
  • 181 Ayares G, Idalsoaga F, Díaz LA, Arnold J, Arab JP. Current medical treatment for alcohol-associated liver disease. J Clin Exp Hepatol 2022; 12 (05) 1333-1348
  • 182 Engelmann C, Berg T. Management of infectious complications associated with acute-on-chronic liver failure. Visc Med 2018; 34 (04) 261-268
  • 183 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 (04) 1299-1309
  • 184 Rivers E, Nguyen B, Havstad S. et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345 (19) 1368-1377
  • 185 Fernandez J, Arroyo V. Bacterial infections in cirrhosis: a growing problem with significant implications. Clin Liver Dis (Hoboken) 2013; 2 (03) 102-105
  • 186 Merli M, Lucidi C, Di Gregorio V. et al. An empirical broad spectrum antibiotic therapy in health-care-associated infections improves survival in patients with cirrhosis: a randomized trial. Hepatology 2016; 63 (05) 1632-1639
  • 187 McDonald LC, Gerding DN, Johnson S. et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66 (07) 987-994