Semin Liver Dis 2016; 36(02): 141-152
DOI: 10.1055/s-0036-1583198
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management of Acute-on-Chronic Liver Failure

Francois Durand
1   Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, University Paris VII Diderot, Paris and Département Hospitalo-Universitaire UNITY, Clichy, France
,
Mitra K. Nadim
2   Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, California
› Author Affiliations
Further Information

Publication History

Publication Date:
12 May 2016 (online)

Abstract

Acute-on-chronic liver failure (ACLF) is defined by the occurrence of organ failure(s) other than the liver in patients with cirrhosis. Even though mortality rates are high, there should no longer be reluctance to admit patients with ACLF in the intensive care unit. The prevalence of multidrug-resistant bacteria is high and broad spectrum antibiotics should be initiated as soon as infection is suspected. In patients with circulatory failure, the assessment of circulatory status is challenging due to the hyperkinetic state and an imbalance between the splanchnic and systemic blood volume. Acute kidney injury is common in patients with ACLF. Acute tubular necrosis should be differentiated from hepatorenal syndrome, which justifies vasoconstrictive agents. Renal replacement therapy and mechanical ventilation should be decided on clinical grounds. Recent trials on extracorporeal liver support failed to demonstrate a survival benefit. Aggressive management may serve as a bridge to transplantation provided patients are likely to survive after transplantation.

 
  • References

  • 1 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 (7) 1426-1437 , 1437.e1–1437.e9
  • 2 Agopian VG, Dhillon A, Baber J , et al. Liver transplantation in recipients receiving renal replacement therapy: outcomes analysis and the role of intraoperative hemodialysis. Am J Transplant 2014; 14 (7) 1638-1647
  • 3 Knaak J, McVey M, Bazerbachi F , et al. Liver transplantation in patients with end-stage liver disease requiring intensive care unit admission and intubation. Liver Transpl 2015; 21 (6) 761-767
  • 4 Nadim MK, Annanthapanyasut W, Matsuoka L , et al. Intraoperative hemodialysis during liver transplantation: a decade of experience. Liver Transpl 2014; 20 (7) 756-764
  • 5 Nadim MK, Genyk YS, Tokin C , et al. Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome. Liver Transpl 2012; 18 (5) 539-548
  • 6 Wehler M, Kokoska J, Reulbach U, Hahn EG, Strauss R. Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems. Hepatology 2001; 34 (2) 255-261
  • 7 Tsai MH, Peng YS, Lien JM , et al. Multiple organ system failure in critically ill cirrhotic patients. A comparison of two multiple organ dysfunction/failure scoring systems. Digestion 2004; 69 (3) 190-200
  • 8 Ho YP, Chen YC, Yang C , et al. Outcome prediction for critically ill cirrhotic patients: a comparison of APACHE II and Child-Pugh scoring systems. J Intensive Care Med 2004; 19 (2) 105-110
  • 9 Rabe C, Schmitz V, Paashaus M , et al. Does intubation really equal death in cirrhotic patients? Factors influencing outcome in patients with liver cirrhosis requiring mechanical ventilation. Intensive Care Med 2004; 30 (8) 1564-1571
  • 10 Chen YC, Tian YC, Liu NJ , et al. Prospective cohort study comparing sequential organ failure assessment and acute physiology, age, chronic health evaluation III scoring systems for hospital mortality prediction in critically ill cirrhotic patients. Int J Clin Pract 2006; 60 (2) 160-166
  • 11 Cholongitas E, Senzolo M, Patch D , et al. Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit. Aliment Pharmacol Ther 2006; 23 (7) 883-893
  • 12 Cholongitas E, Betrosian A, Senzolo M , et al. Prognostic models in cirrhotics admitted to intensive care units better predict outcome when assessed at 48 h after admission. J Gastroenterol Hepatol 2008; 23 (8 Pt 1) 1223-1227
  • 13 Juneja D, Gopal PB, Kapoor D, Raya R, Sathyanarayanan M, Malhotra P. Outcome of patients with liver cirrhosis admitted to a specialty liver intensive care unit in India. J Crit Care 2009; 24 (3) 387-393
  • 14 Karvellas CJ, Pink F, McPhail M , et al. Bacteremia, acute physiology and chronic health evaluation II and modified end stage liver disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure. Crit Care Med 2010; 38 (1) 121-126
  • 15 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
  • 16 Filloux B, Chagneau-Derrode C, Ragot S , et al. Short-term and long-term vital outcomes of cirrhotic patients admitted to an intensive care unit. Eur J Gastroenterol Hepatol 2010; 22 (12) 1474-1480
  • 17 Tu KH, Jenq CC, Tsai MH , et al. Outcome scoring systems for short-term prognosis in critically ill cirrhotic patients. Shock 2011; 36 (5) 445-450
  • 18 Cholongitas E, Agarwal B, Antoniadis N, Burroughs AK. Patients with cirrhosis admitted to an intensive care unit. J Hepatol 2012; 57 (1) 230-231 , author reply 231–232
  • 19 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 (1) 95-102
  • 20 Olmez S, Gümürdülü Y, Tas A, Karakoc E, Kara B, Kidik A. Prognostic markers in cirrhotic patients requiring intensive care: a comparative prospective study. Ann Hepatol 2012; 11 (4) 513-518
  • 21 Levesque E, Saliba F, Ichaï P, Samuel D. Outcome of patients with cirrhosis requiring mechanical ventilation in ICU. J Hepatol 2014; 60 (3) 570-578
  • 22 Galbois A, Aegerter P, Martel-Samb P , et al; Collège des Utilisateurs des Bases des données en Réanimation (CUB-Réa) Group. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study*. Crit Care Med 2014; 42 (7) 1666-1675
  • 23 Boone MD, Celi LA, Ho BG , et al. Model for End-Stage Liver Disease score predicts mortality in critically ill cirrhotic patients. J Crit Care 2014; 29 (5) 881.e7-881.e13
  • 24 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 (4) 554-562
  • 25 Pan HC, Jenq CC, Tsai MH , et al. Scoring systems for 6-month mortality in critically ill cirrhotic patients: a prospective analysis of chronic liver failure - sequential organ failure assessment score (CLIF-SOFA). Aliment Pharmacol Ther 2014; 40 (9) 1056-1065
  • 26 McPhail MJ, Shawcross DL, Abeles RD , et al. Increased survival for patients with cirrhosis and organ failure in liver intensive care and validation of the chronic liver failure-sequential organ failure scoring system. Clin Gastroenterol Hepatol 2015; 13 (7) 1353-1360.e8
  • 27 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 (5) 1038-1047
  • 28 Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions. J Hepatol 2014; 61 (4) 912-924
  • 29 Sakka SG, Reinhart K, Meier-Hellmann A. Comparison of pulmonary artery and arterial thermodilution cardiac output in critically ill patients. Intensive Care Med 1999; 25 (8) 843-846
  • 30 Monnet X, Teboul JL. Assessment of volume responsiveness during mechanical ventilation: recent advances. Crit Care 2013; 17 (2) 217
  • 31 Biancofiore G, Critchley LA, Lee A , et al. Evaluation of a new software version of the FloTrac/Vigileo (version 3.02) and a comparison with previous data in cirrhotic patients undergoing liver transplant surgery. Anesth Analg 2011; 113 (3) 515-522
  • 32 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 (7) 901-909
  • 33 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 (4) 968-974
  • 34 Galbois A, Bigé N, Pichereau C , et al. Exploration of skin perfusion in cirrhotic patients with septic shock. J Hepatol 2015; 62 (3) 549-555
  • 35 Cecconi M, De Backer D, Antonelli M , et al. Consensus on circulatory shock and hemodynamic monitoring. Task Force of the European Society of Intensive Care Medicine. Intensive Care Med 2014; 40 (12) 1795-1815
  • 36 Holst LB, Haase N, Wetterslev J , et al; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014; 371 (15) 1381-1391
  • 37 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
  • 38 Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol 2014; 61 (2) 396-407
  • 39 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 (6) 403-409
  • 40 Boyer TD, Sanyal AJ, Garcia-Tsao G , et al; Terlipressin Study Group. Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. J Hepatol 2011; 55 (2) 315-321
  • 41 Sola-Vera J, Miñana J, Ricart E , et al. Randomized trial comparing albumin and saline in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients with ascites. Hepatology 2003; 37 (5) 1147-1153
  • 42 Moreau R, Valla DC, Durand-Zaleski I , et al. Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid: a randomised controlled pilot trail. Liver Int 2006; 26 (1) 46-54
  • 43 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 (4) 759-765
  • 44 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 (2) 124-134
  • 45 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 (9) 779-789
  • 46 O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002; 359 (9313) 1209-1210
  • 47 Leone M, Albanèse J, Delmas A, Chaabane W, Garnier F, Martin C. Terlipressin in catecholamine-resistant septic shock patients. Shock 2004; 22 (4) 314-319
  • 48 Fede G, Spadaro L, Tomaselli T , et al. Adrenocortical dysfunction in liver disease: a systematic review. Hepatology 2012; 55 (4) 1282-1291
  • 49 Harry R, Auzinger G, Wendon J. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology 2002; 36 (2) 395-402
  • 50 Marik PE, Gayowski T, Starzl TE ; Hepatic Cortisol Research and Adrenal Pathophysiology Study Group. The hepatoadrenal syndrome: a common yet unrecognized clinical condition. Crit Care Med 2005; 33 (6) 1254-1259
  • 51 Tsai MH, Peng YS, Chen YC , et al. Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. Hepatology 2006; 43 (4) 673-681
  • 52 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
  • 53 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 (5) 1288-1295
  • 54 Harry R, Auzinger G, Wendon J. The effects of supraphysiological doses of corticosteroids in hypotensive liver failure. Liver Int 2003; 23 (2) 71-77
  • 55 Annane D, Sébille V, Charpentier C , et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288 (7) 862-871
  • 56 Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol 2015; 26 (9) 2231-2238
  • 57 Macedo E, Malhotra R, Bouchard J, Wynn SK, Mehta RL. Oliguria is an early predictor of higher mortality in critically ill patients. Kidney Int 2011; 80 (7) 760-767
  • 58 Macedo E, Malhotra R, Claure-Del Granado R, Fedullo P, Mehta RL. Defining urine output criterion for acute kidney injury in critically ill patients. Nephrol Dial Transplant 2011; 26 (2) 509-515
  • 59 Belcher JM, Garcia-Tsao G, Sanyal AJ , et al; TRIBE-AKI Consortium. Association of AKI with mortality and complications in hospitalized patients with cirrhosis. Hepatology 2013; 57 (2) 753-762
  • 60 Belcher JM, Garcia-Tsao G, Sanyal AJ , et al; TRIBE-AKI Consortium. Urinary biomarkers and progression of AKI in patients with cirrhosis. Clin J Am Soc Nephrol 2014; 9 (11) 1857-1867
  • 61 Verna EC, Brown RS, Farrand E , et al. Urinary neutrophil gelatinase-associated lipocalin predicts mortality and identifies acute kidney injury in cirrhosis. Dig Dis Sci 2012; 57 (9) 2362-2370
  • 62 Fagundes C, Pépin MN, Guevara M , et al. Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis. J Hepatol 2012; 57 (2) 267-273
  • 63 Barreto R, Elia C, Solà E , et al. Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections. J Hepatol 2014; 61 (1) 35-42
  • 64 Ariza X, Solà E, Elia C , et al. Analysis of a urinary biomarker panel for clinical outcomes assessment in cirrhosis. PLoS ONE 2015; 10 (6) e0128145
  • 65 Gluud LL, Christensen K, Christensen E, Krag A. Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome. Hepatology 2010; 51 (2) 576-584
  • 66 Ginès P, Fernández J, Durand F, Saliba F. Management of critically-ill cirrhotic patients. J Hepatol 2012; 56 (Suppl. 01) S13-S24
  • 67 Duvoux C, Zanditenas D, Hézode C , et al. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study. Hepatology 2002; 36 (2) 374-380
  • 68 Alessandria C, Ottobrelli A, Debernardi-Venon W , et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol 2007; 47 (4) 499-505
  • 69 Singh V, Ghosh S, Singh B , et al. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. J Hepatol 2012; 56 (6) 1293-1298
  • 70 Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol 2008; 103 (7) 1689-1697
  • 71 Davenport A, Will EJ, Davison AM. Effect of renal replacement therapy on patients with combined acute renal and fulminant hepatic failure. Kidney Int Suppl 1993; 41: S245-S251
  • 72 Bellomo R, Cass A, Cole L , et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009; 361 (17) 1627-1638
  • 73 Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology 2009; 50 (6) 2014-2021
  • 74 Vilstrup H, Gluud C, Hardt F , et al. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis. J Hepatol 1990; 10 (3) 291-296
  • 75 Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol 2015; 62 (2) 437-447
  • 76 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 (9) 1458-1463
  • 77 Bass NM, Mullen KD, Sanyal A , et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362 (12) 1071-1081
  • 78 Goodwin HE, Gill RS, Murakami PN, Thompson CB, Lewin III JJ, Mirski MA. Dexmedetomidine preserves attention/calculation when used for cooperative and short-term intensive care unit sedation. J Crit Care 2013; 28 (6) 1113.e7-1113.e10
  • 79 Pasin L, Greco T, Feltracco P , et al. Dexmedetomidine as a sedative agent in critically ill patients: a meta-analysis of randomized controlled trials. PLoS ONE 2013; 8 (12) e82913
  • 80 Adebayo D, Morabito V, Davenport A, Jalan R. Renal dysfunction in cirrhosis is not just a vasomotor nephropathy. Kidney Int 2015; 87 (3) 509-515
  • 81 Qin N, Yang F, Li A , et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014; 513 (7516) 59-64
  • 82 Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut 2001; 48 (2) 206-211
  • 83 Kakiyama G, Pandak WM, Gillevet PM , et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J Hepatol 2013; 58 (5) 949-955
  • 84 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 (6) 1310-1324
  • 85 Wasmuth HE, Kunz D, Yagmur E , et al. Patients with acute on chronic liver failure display “sepsis-like” immune paralysis. J Hepatol 2005; 42 (2) 195-201
  • 86 Rolas L, Makhezer N, Hadjoudj S , et al. Inhibition of mammalian target of rapamycin aggravates the respiratory burst defect of neutrophils from decompensated patients with cirrhosis. Hepatology 2013; 57 (3) 1163-1171
  • 87 O'Brien AJ, Fullerton JN, Massey KA , et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med 2014; 20 (5) 518-523
  • 88 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 (6) 2328-2335
  • 89 Jalan R, Gines P, Olson JC , et al. Acute-on chronic liver failure. J Hepatol 2012; 57 (6) 1336-1348
  • 90 Umgelter A, Reindl W, Miedaner M, Schmid RM, Huber W. Failure of current antibiotic first-line regimens and mortality in hospitalized patients with spontaneous bacterial peritonitis. Infection 2009; 37 (1) 2-8
  • 91 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 (4) 825-832
  • 92 Ramírez MJ, Titos E, Clària J, Navasa M, Fernández J, Rodés J. Increased apoptosis dependent on caspase-3 activity in polymorphonuclear leukocytes from patients with cirrhosis and ascites. J Hepatol 2004; 41 (1) 44-48
  • 93 Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R. Severe sepsis in cirrhosis. Hepatology 2009; 50 (6) 2022-2033
  • 94 Gandoura S, Weiss E, Rautou PE , et al. Gene- and exon-expression profiling reveals an extensive LPS-induced response in immune cells in patients with cirrhosis. J Hepatol 2013; 58 (5) 936-948
  • 95 Fernández J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol 2012; 56 (Suppl. 01) S1-S12
  • 96 Bernard B, Grangé JD, Khac EN, Amiot X, Opolon P, Poynard T. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology 1999; 29 (6) 1655-1661
  • 97 Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet 1999; 353 (9147) 139-142
  • 98 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 (4) 1049-1056 , quiz 1285
  • 99 de Franchis R ; Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension. J Hepatol 2010; 53 (4) 762-768
  • 100 Fernández J, Navasa M, Planas R , et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology 2007; 133 (3) 818-824
  • 101 Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F , et al. Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review. Aliment Pharmacol Ther 2011; 34 (5) 509-518
  • 102 de Franchis R ; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63 (3) 743-752
  • 103 Soriano G, Guarner C, Tomás A , et al. Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. Gastroenterology 1992; 103 (4) 1267-1272
  • 104 Wu CK, Wang JH, Lee CH , et al. The outcome of prophylactic intravenous cefazolin and ceftriaxone in cirrhotic patients at different clinical stages of disease after endoscopic interventions for acute variceal hemorrhage. PLoS ONE 2013; 8 (4) e61666
  • 105 [Anonymous] 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 (3) 397-417
  • 106 Rampini SK, Bloemberg GV, Keller PM , et al. Broad-range 16S rRNA gene polymerase chain reaction for diagnosis of culture-negative bacterial infections. Clin Infect Dis 2011; 53 (12) 1245-1251
  • 107 Patel R. MALDI-TOF MS for the diagnosis of infectious diseases. Clin Chem 2015; 61 (1) 100-111
  • 108 Loomba R, Wesley R, Bain A, Csako G, Pucino F. Role of fluoroquinolones in the primary prophylaxis of spontaneous bacterial peritonitis: meta-analysis. Clin Gastroenterol Hepatol 2009; 7 (4) 487-493
  • 109 Novella M, Solà R, Soriano G , et al. Continuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin. Hepatology 1997; 25 (3) 532-536
  • 110 Grangé JD, Roulot D, Pelletier G , et al. Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial. J Hepatol 1998; 29 (3) 430-436
  • 111 Terg R, Fassio E, Guevara M , et al. Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study. J Hepatol 2008; 48 (5) 774-779
  • 112 Panasiuk A, Wysocka J, Maciorkowska E , et al. Phagocytic and oxidative burst activity of neutrophils in the end stage of liver cirrhosis. World J Gastroenterol 2005; 11 (48) 7661-7665
  • 113 Cheruvattath R, Balan V. Infections in patients with end-stage liver disease. J Clin Gastroenterol 2007; 41 (4) 403-411
  • 114 Meersseman W, Lagrou K, Spriet I , et al. Significance of the isolation of Candida species from airway samples in critically ill patients: a prospective, autopsy study. Intensive Care Med 2009; 35 (9) 1526-1531
  • 115 Cornely OA, Bassetti M, Calandra T , et al; ESCMID Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18 (7) (Suppl. 07) 19-37
  • 116 Pappas PG, Kauffman CA, Andes D , et al; Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48 (5) 503-535
  • 117 Tripodi A, Primignani M, Chantarangkul V , et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137 (6) 2105-2111
  • 118 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 (4) 1039-1046
  • 119 Giannini EG, Savarino V. Thrombocytopenia in liver disease. Curr Opin Hematol 2008; 15 (5) 473-480
  • 120 Colucci M, Binetti BM, Branca MG , et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 2003; 38 (1) 230-237
  • 121 Valla DC, Rautou PE. The coagulation system in patients with end-stage liver disease. Liver Int 2015; 35 (Suppl. 01) 139-144
  • 122 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365 (2) 147-156
  • 123 Joist JH. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state. Am J Gastroenterol 1999; 94 (10) 2801-2803
  • 124 Rijken DC, Kock EL, Guimarães AH , et al. Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests. J Thromb Haemost 2012; 10 (10) 2116-2122
  • 125 Youssef W. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol 2003; 98 (6) 1391-1394
  • 126 Tripodi A, Primignani M, Chantarangkul V , et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44 (2) 440-445
  • 127 Nascimento B, Goodnough LT, Levy JH. Cryoprecipitate therapy. Br J Anaesth 2014; 113 (6) 922-934
  • 128 Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014; 54 (5) 1389-1405 , quiz 1388
  • 129 Spahn DR, Bouillon B, Cerny V , et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care 2013; 17 (2) R76
  • 130 Gunawan B, Runyon B. The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis. Aliment Pharmacol Ther 2006; 23 (1) 115-120
  • 131 Bañares R, Nevens F, Larsen FS , et al; RELIEF study group. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 2013; 57 (3) 1153-1162
  • 132 Kribben A, Gerken G, Haag S , et al; HELIOS Study Group. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 2012; 142 (4) 782-789.e3
  • 133 Heemann U, Treichel U, Loock J , et al. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology 2002; 36 (4 Pt 1) 949-958
  • 134 Mitzner SR, Stange J, Klammt S , et al. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl 2000; 6 (3) 277-286
  • 135 Jalan R, Sen S, Steiner C, Kapoor D, Alisa A, Williams R. Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis. J Hepatol 2003; 38 (1) 24-31
  • 136 Glorioso JM, Mao SA, Rodysill B , et al. Pivotal preclinical trial of the spheroid reservoir bioartificial liver. J Hepatol 2015; 63 (2) 388-398
  • 137 Zhou N, Li J, Zhang Y , et al. Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure: A randomised study. J Hepatol 2015; 63 (2) 378-387
  • 138 Lee KC, Baker LA, Stanzani G , et al. Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study. J Hepatol 2015; 63 (3) 634-642
  • 139 Angeli P, Volpin R, Gerunda G , et al. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999; 29 (6) 1690-1697
  • 140 Colle I, Durand F, Pessione F , et al. Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with terlipressin: a retrospective analysis. J Gastroenterol Hepatol 2002; 17 (8) 882-888
  • 141 Halimi C, Bonnard P, Bernard B , et al. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol 2002; 14 (2) 153-158
  • 142 Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci 2007; 52 (3) 742-748
  • 143 Uriz J, Ginès P, Cárdenas A , et al. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol 2000; 33 (1) 43-48
  • 144 Mulkay JP, Louis H, Donckier V , et al. Long-term terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study. Acta Gastroenterol Belg 2001; 64 (1) 15-19
  • 145 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
  • 146 Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol 2003; 18 (2) 152-156
  • 147 Neri S, Pulvirenti D, Malaguarnera M , et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci 2008; 53 (3) 830-835
  • 148 Sanyal AJ, Boyer T, Garcia-Tsao G , et al; Terlipressin Study Group. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008; 134 (5) 1360-1368
  • 149 Martín-Llahí M, Pépin MN, Guevara M , et al; TAHRS Investigators. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008; 134 (5) 1352-1359
  • 150 Cavallin M, Kamath PS, Merli M , et al; Italian Association for the Study of the Liver Study Group on Hepatorenal Syndrome. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology 2015; 62 (2) 567-574