Bacterial Infections, Sepsis, and Multiorgan Failure in Cirrhosis

ABSTRACT

Bacterial infections are an important complication of cirrhosis, particularly in hospitalized patients. In this article we review the prevalence, risk factors, and pathogenesis of bacterial infections in cirrhosis, focusing on the mechanisms of bacterial translocation such as impaired immunity and bacterial overgrowth, as well as maneuvers that may inhibit bacterial translocation and could be used not only to prevent infections but also to ameliorate the hyperdynamic circulatory state of cirrhosis. We also review the clinical features and management of the most common infection in cirrhosis, spontaneous bacterial peritonitis (SBP), specifically the evidence behind the therapy of acute SBP, the role of albumin, and the role of antibiotics in the prophylaxis of high-risk patients. It has been recognized that SBP and other bacterial infections lead to the systemic inflammatory response syndrome, sepsis, and multiorgan failure. We review the pathogenesis and management of these complications, the role of adrenal insufficiency, and the utility of intensive care prognostic models.

KEYWORDS

Bacterial infection - spontaneous bacterial peritonitis - cirrhosis - bacterial translocation - sepsis - SIRS - multiorgan failure

REFERENCES

• 1 Borzio M, Salerno F, Piantoni L et al.. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study.  Dig Liver Dis. 2001;  33 41-48
• 2 Fernandez J, Navasa M, Gomez J et al.. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis.  Hepatology. 2002;  35 140-148
• 3 Bernard B, Grange J D, Khac E N et al.. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis.  Hepatology. 1999;  29 1655-1661
• 4 Foreman M G, Mannino D M, Moss M. Cirrhosis as a risk factor for sepsis and death: analysis of the national hospital discharge survey.  Chest. 2003;  124 1016-1020
• 5 Deschenes M, Villeneuve J P. Risk factors for the development of bacterial infections in hospitalized patients with cirrhosis.  Am J Gastroenterol. 1999;  94 2193-2197
• 6 Yoshida H, Hamada T, Inzuka S et al.. Bacterial infection in cirrhosis, with and without hepatocellular carcinoma.  Am J Gastroenterol. 1993;  88 2067-2071
• 7 Caly W R, Strauss E. A prospective study of bacterial infections in patients with cirrhosis.  J Hepatol. 1993;  18 353-358
• 8 Rimola A, Bory F, Teres J et al.. Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage.  Hepatology. 1985;  5 463-467
• 9 Soriano G, Guarner C, Tomas A et al.. Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage.  Gastroenterology. 1992;  103 1267-1272
• 10 Blaise M, Pateron D, Trinchet J C et al.. Systemic antibiotic therapy prevents bacterial infection in cirrhotic patients with gastrointestinal hemorrhage.  Hepatology. 1994;  20 34-38
• 11 Bernard B, Cadranel J F, Valla D et al.. Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study.  Gastroenterology. 1995;  108 1828-1834
• 12 Pauwels A, Mostefa-Kara N, Debenes B et al.. Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection.  Hepatology. 1996;  24 802-806
• 13 Hsieh W J, Lin H C, Hwang S J et al.. The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding.  Am J Gastroenterol. 1998;  93 962-966
• 14 Goulis J, Armonis A, Patch D et al.. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage.  Hepatology. 1998;  27 1207-1212
• 15 Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis.  Best Pract Res Clin Gastroenterol. 2004;  18 353-372
• 16 Christou L, Pappas G, Falagas M E. Bacterial infection-related morbidity and mortality in cirrhosis.  Am J Gastroenterol. 2007;  102 1510-1517
• 17 Fierer J, Finley F. Deficient serum bactericidal activity against Escherichia coli in patients with cirrhosis of the liver.  J Clin Invest. 1979;  63 912-921
• 18 Hassner A, Kletter Y, Shlag D et al.. Impaired monocyte function in liver cirrhosis.  BMJ. 1981;  282 1262-1263
• 19 Akalin H E, Laleli Y, Telatar H. Serum bactericidal and opsonic activities in patients with non-alcoholic cirrhosis.  Q J Med. 1985;  56 431-437
• 20 Garcia-Gonzalez M, Boixeda D, Herrero D et al.. Effect of granulocyte-macrophage colony-stimulating factor on leukocyte function in cirrhosis.  Gastroenterology. 1993;  105 527-531
• 21 Finlayson N D, Krohn K, Fauconnet M H et al.. Significance of serum complement levels in chronic liver disease.  Gastroenterology. 1972;  63 653-659
• 22 Mellencamp M A, Preheim L C. Pneumococcal pneumonia in a rat model of cirrhosis: effects of cirrhosis on pulmonary defense mechanisms against Streptococcus pneumoniae.  J Infect Dis. 1991;  163 102-108
• 23 Homann C, Varming K, Hogasen K et al.. Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to infection and increased mortality.  Gut. 1997;  40 544-549
• 24 Rimola A, Soto R, Bory F et al.. Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis.  Hepatology. 1984;  4 53-58
• 25 Zweifach B W, Benacerraf B. Effect of hemorrhagic shock on the phagocytic function of Kupffer cells.  Circ Res. 1958;  6 83-87
• 26 Altura B M, Hershey S G. Sequential changes in reticuloendothelial system after acute hemorrhage.  Proc Soc Exp Biol Med. 1972;  139 935-939
• 27 Llovet J M, Bartoli R, Planas R et al.. Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock.  Hepatology. 1996;  23 781-787
• 28 Garcia-Tsao G. Bacterial infections in cirrhosis: treatment and prophylaxis.  J Hepatol. 2005;  42 S85-S92
• 29 Berg R D, Garlington A W. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model.  Infect Immun. 1979;  23 403-411
• 30 Kraehenbuhl J P, Corbett M. Immunology: keeping the gut microflora at bay.  Science. 2004;  303 1624-1625
• 31 Garcia-Tsao G, Albillos A, Barden G E et al.. Bacterial translocation in acute and chronic portal hypertension.  Hepatology. 1993;  17 1081-1085
• 32 Garcia-Tsao G, Lee F Y, Barden G E et al.. Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites.  Gastroenterology. 1995;  108 1835-1841
• 33 Battista S, Bar F, Mengozzi G, Zanon E, Grosso M, Molino G. Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric oxide levels in hepatic and portal veins.  J Hepatol. 1997;  26 75-80
• 34 Lumsden A B, Henderson J M, Kutner M H et al.. Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis.  Hepatology. 1988;  8 232-236
• 35 Wiest R, Das S, Cadelina G et al.. Bacterial translocation to lymph nodes of cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility.  J Clin Invest. 1999;  104 1223-1233
• 36 Wiest R, Cadelina G, Milstien S et al.. Bacterial translocation up-regulated GTP-cyclohydrolase I in mesenteric vasculature of cirrhotic rats.  Hepatology. 2003;  38 1508-1515
• 37 Chin-Dusting J P, Rasaratnam B, Jennings G L et al.. Effect of fluoroquinolone on the enhanced nitric oxide-induced peripheral vasodilation seen in cirrhosis.  Ann Intern Med. 1997;  127 985-988
• 38 Rabiller A, Nunes H, Lebrec D et al.. Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome.  Am J Respir Crit Care Med. 2002;  166 514-517
• 39 Albillos A, de la Hera A, Gonzalez M et al.. Increased lipopolysaccharide binding protein in cirrhotic patients with more marked immune and hemodynamic derangement.  Hepatology. 2003;  37 208-217
• 40 Runyon B A, Squier S, Borzio M et al.. Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis.  J Hepatol. 1994;  21 792-796
• 41 Llovet J M, Bartoli R, March F et al.. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiological evidence.  J Hepatol. 1998;  28 307-313
• 42 Steffen E K, Berg R D, Deitch E A et al.. Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node.  J Infect Dis. 1988;  157 1032-1038
• 43 Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis.  Hepatology. 2005;  41 422-433
• 44 Wells C L, Maddaus M A, Reynolds C M et al.. Role of anaerobic flora in the translocation of aerobic and facultatively anaerobic intestinal bacteria.  Infect Immun. 1987;  55 2689-2694
• 45 Cirera I, Bauer T M, Navasa M et al.. Bacterial translocation of enteric organisms in patients with cirrhosis.  J Hepatol. 2001;  34 32-37
• 46 Garcia-Tsao G. Bacterial translocation: cause or consequence of decompensation in cirrhosis?.  J Hepatol. 2001;  34 150-155
• 47 Albillos A, de-la-Hera A, Alvarez-Mon M. Serum lipopolysaccharide-binding protein prediction of severe bacterial infection in cirrhotic patients with ascites.  Lancet. 2004;  363 1608-1610
• 48 Guarner C, González-Navajas J M, Sanchez E et al.. The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation.  Hepatology. 2006;  44 633-639
• 49 Such J, Francés R, Muñoz C et al.. Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites.  Hepatology. 2002;  36 135-141
• 50 Francés R, Muñoz C, Zapater P et al.. Bacterial DNA activates cell mediated immune responses and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites.  Gut. 2004;  53 860-864
• 51 Francés R, González-Navajas J M, Zapater P et al.. Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.  J Clin Immunol. 2007;  27 438-444
• 52 Bellot P, Garcia-Pagan J C, Francés R et al.. Bacterial translocation induces proinflammatory cytokines and worsens systemic hemodynamics in cirrhotic patients with ascites.  J Hepatol. 2007;  46 S90
• 53 Yang C Y, Chang C S, Chen G H. Small intestinal bacterial overgrowth in patients with liver cirrhosis, diagnosed with glucose H2 or CH4 breath tests.  Scand J Gastroenterol. 1998;  33 867-871
• 54 Chang C S, Chen G H, Lien H C et al.. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis.  Hepatology. 1998;  28 1187-1190
• 55 Galati J S, Holdeman K P, Bottjen P L et al.. Gastric emptying and orocecal transit in portal hypertension and end-stage chronic liver disease.  Liver Transpl Surg. 1997;  3 34-38
• 56 Madrid A M, Brahm J, Buckel E et al.. Orthotopic liver transplantation improves small bowel motility disorders in cirrhotic patients.  Am J Gastroenterol. 1997;  92 1044-1045
• 57 Madrid A M, Cumsille F, Defilippi C. Altered small bowel motility in patients with liver cirrhosis depends on severity of liver disease.  Dig Dis Sci. 1997;  42 738-742
• 58 Gunnarsdottir S A, Sadik R, Shev S et al.. Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension.  Am J Gastroenterol. 2003;  98 1362-1370
• 59 Riordan S M, Williams R. The intestinal flora and bacterial infection in cirrhosis.  J Hepatol. 2006;  45 744-757
• 60 Natarajan S K, Ramamoorthy P, Thomas S et al.. Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: changes in glycosylation and luminal bacteria.  Hepatology. 2006;  43 837-846
• 61 Bauer T M, Schwacha H, Steinbruckner B et al.. Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia.  Am J Gastroenterol. 2002;  97 2364-2370
• 62 Perez-Paramo M, Munoz J, Albillos A et al.. Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites.  Hepatology. 2000;  31 43-48
• 63 Misra V, Misra S, Dwivedi M et al.. Histomorphometric study of portal hypertensive enteropathy.  Am J Clin Pathol. 1997;  108 652-657
• 64 Zhang S C, Wang W, Ren W Y et al.. Effect of cisapride on intestinal bacterial and endotoxin translocation in cirrhosis.  World J Gastroenterol. 2003;  9 534-538
• 65 Campillo B, Perner P, Bories P N et al.. Intestinal permeability in liver cirrhosis: relationship with severe septic complications.  Eur J Gastroenterol Hepatol. 1999;  11 755-759
• 66 Pascual S, Such J, Esteban A et al.. Intestinal permeability is increased in patients with advanced cirrhosis.  Hepatogastroenterology. 2003;  50 1482-1486
• 67 Zuckerman M J, Menzies I S, Ho H et al.. Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes.  Dig Dis Sci. 2004;  49 621-626
• 68 Kalaitzakis E, Johansson J E, Bjarnason I et al.. Intestinal permeability in cirrhotic patients with and without ascites.  Scand J Gastroenterol. 2006;  41 326-330
• 69 Albillos A, de la Hera A, Reyes E et al.. Tumor necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.  J Hepatol. 2004;  40 624-631
• 70 Saitoh O, Sugi K, Lojima K et al.. Increased prevalence of intestinal inflammation in patients with liver cirrhosis.  World J Gastroenterol. 1999;  5 391-396
• 71 Runyon B A, Borzio M, Young S et al.. Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis.  Hepatology. 1995;  21 1719-1724
• 72 Guarner C, Runyon B A, Heck M et al.. Effect of long-term trimethoprim-sulfamethoxazole prophylaxis on ascites formation, bacterial translocation, spontaneous bacterial peritonitis, and survival in cirrhotic rats.  Dig Dis Sci. 1999;  44 1957-1962
• 73 Rimola A, Bory F, Teres J et al.. Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastroinestinal hemorrhage.  Hepatology. 1985;  5 457-462
• 74 Ginèes 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;  12 716-724
• 75 Fernandez J, Navasa M, Planas R et al.. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis.  Gastroenterology. 2007;  133 818-824
• 76 Levitsky J. Probiotics: application of “healthy” bacteria to liver transplant recipients.  Hepatology. 2006;  44 507-510
• 77 Rayes N, Seehofer D, Hansen S et al.. Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients.  Transplantation. 2002;  74 123-127
• 78 Rayes N, Seehofer D, Theruvath T et al.. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation: a randomized, double-blind trial.  Am J Transplant. 2005;  5 125-130
• 79 Bauer T M, Fernandez J, Navasa M et al.. Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis.  J Hepatol. 2002;  36 501-506
• 80 Chiva M, Soriano G, Rochat I et al.. Effect of lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis.  J Hepatol. 2002;  37 456-462
• 81 Wiest R, Chen F, Cadelina G et al.. Effect of lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension.  Dig Dis Sci. 2003;  48 1136-1141
• 82 Bartoli R, Mane J, Cabre E et al.. Effect of the administration of fermentable and non-fermentable dietary fibre on intestinal bacterial translocation in ascitic cirrhotic rats.  Clin Nutr. 2007;  26 383-387
• 83 Mackay A D, Taylor M B, Kibbler C C et al.. Lactobacillus endocarditis caused by a probiotic organism.  Clin Microbiol Infect. 1999;  5 290-292
• 84 Rautio M, Jousimies-Somer H, Kauma H et al.. Liver abscess due to a lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG.  Clin Infect Dis. 1999;  28 1159-1160
• 85 Pardo A, Bartoli R, Lorenzo-Zuniga V et al.. Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis.  Hepatology. 2000;  31 858-863
• 86 Madrid A M, Hurtado C, Venegas M et al.. Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function.  Am J Gastroenterol. 2001;  96 1251-1255
• 87 Sandhu B S, Gupta R, Sharma J et al.. Norfloxacin and cisapride combination decreases the incidence of spontaneous bacterial peritonitis in cirrhotic ascites.  J Gastroenterol Hepatol. 2005;  20 599-605
• 88 Cholongitas E, Papatheodoridis G V, Manesis E K et al.. Spontaneous bacterial peritonitis in cirrhotic patients: is prophylactic propranolol therapy beneficial?.  J Gastroenterol Hepatol. 2006;  21 581-587
• 89 Abraldes J G, Tarantino I, Turnes J et al.. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis.  Hepatology. 2003;  37 902-908
• 90 Gonzalez-Suarez B, Guarner C, Villanueva C et al.. Pharmacologic treatment of portal hypertension in the prevention of community-acquired spontaneous bacterial peritonitis.  Eur J Gastroenterol Hepatol. 2006;  18 49-55
• 91 Turnes J, Garcia-Pagan J C, Abraldes J G et al.. Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis.  Am J Gastroenterol. 2006;  101 506-512
• 92 Slocum M M, Sittig K M, Specian R D et al.. Absence of intestinal bile promotes bacterial translocation.  Am Surg. 1992;  58 305-310
• 93 Lorenzo-Zuniga V, Bartoli R, Planas R et al.. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats.  Hepatology. 2003;  37 551-557
• 94 Rimola A, Garcia-Tsao G, Navasa M et al.. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document.  J Hepatol. 2000;  32 142-153
• 95 Ghassemi S, Garcia-Tsao G. Prevention and treatment of infections in patients with cirrhosis.  Best Pract Res Clin Gastroenterol. 2007;  21 77-93
• 96 Nousbaum J B, Cadranel J F, Nahon P et al.. Diagnostic accuracy of the Multistix 8 SG reagent strip in diagnosis of spontaneous bacterial peritonitis.  Hepatology. 2007;  45 1275-1281
• 97 Garcia-Tsao G. Spontaneous bacterial peritonitis.  Gastroenterol Clin North Am. 1992;  21 257-275
• 98 Garcia-Tsao G. Spontaneous bacterial peritonitis: a historical perspective.  J Hepatol. 2004;  41 522-527
• 99 Rimola A, Salmeron J M, Clemente G et al.. Two different dosages of cefotaxime in the treatment of spontaneous bacterial peritonitis in cirrhosis: results of a prospective, randomized, multicenter study.  Hepatology. 1995;  21 674-679
• 100 Ricart E, Soriano G, Novella M et al.. Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients.  J Hepatol. 2000;  32 596-602
• 101 Navasa M, Follo A, Llovet J M et al.. Randomized comparative study of oral ofloxacin versus intravenous cefotaxime in spontaneous bacterial peritonitis.  Gastroenterology. 1996;  111 1011-1017
• 102 Ruiz-del-Arbol L, Urman J, Fernandez J et al.. Systemic, renal and hepatic hemodynamic derangements in cirrhotic patients with spontaneous bacterial peritonitis.  Hepatology. 2003;  38 1210-1218
• 103 Fernandez J, Navasa M, Garcia-Pagan J C et al.. Effect of intravenous albumin on systemic and hepatic hemodynamics and vasoactive neurohormonal systems in patients with cirrhosis and spontaneous bacterial peritonitis.  J Hepatol. 2004;  41 384-390
• 104 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
• 105 Casas M, Soriano G, Ayala E et al.. Intravenous albumin is not necessary in cirrhotic patients with spontaneous bacterial peritonitis and low-risk of mortality.  J Hepatol. 2007;  46 S91
• 106 Fernandez J, Ruiz Del Arbol L, Gomez C et al.. Norfloxacin versus ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage.  Gastroenterology. 2006;  131 1049-1056
• 107 Llach J, Rimola A, Navasa M et al.. Incidence and predictive factors of the first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration.  Hepatology. 1992;  16 724-727
• 108 Rolachon A, Cordier L, Bacq Y et al.. Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial.  Hepatology. 1995;  22 1171-1174
• 109 Singh N, Gayowski T, Yu V L et al.. Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial.  Ann Intern Med. 1995;  122 595-598
• 110 Novella M, Sola R, Soriano G et al.. Continuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin.  Hepatology. 1997;  25 532-536
• 111 Grange J D, 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;  29 430-436
• 112 Tito L, Rimola A, Ginès P et al.. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors.  Hepatology. 1988;  8 27-31
• 113 Terg R, Llano K, Cobas S M et al.. Effects of oral ciprofoxacin on aerobic gram-negative fecal flora in patients with cirrhosis: results of short and long term administration with daily and weekly dosages.  J Hepatol. 1998;  29 437-442
• 114 Bauer T M, Follo A, Navasa M et al.. Daily norfloxacin is more effective than weekly rufloxacin in prevention of spontaneous bacterial peritonitis recurrence.  Dig Dis Sci. 2002;  47 1356-1361
• 115 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.  Crit Care Med. 1992;  20 864-874
• 116 Brun-Buisson C, Doyon F, Carlet J et al.. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis.  JAMA. 1995;  274 968-974
• 117 Alberti C, Brun-Buisson C, Goodman S V et al.. Influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients.  Am J Respir Crit Care Med. 2003;  168 77-84
• 118 Dhainaut J F, Claessens Y E, Nelson D R. Underlying disorders and their impact on the host response to infection.  Clin Infect Dis. 2005;  41 S481-S489
• 119 Sanchez W, Kamath P S. Prevention and treatment of acute liver failure in patients with chronic liver disease. In: Arroyo V, Sanchez-Fueyo A, Fernandez-Gomez J, Forns X, Ginès P, Rodés J Advances in the Therapy of Liver Diseases. Barcelona; Ars Medica 2007: 73-77
• 120 Wong F, Bernardi M, Balk R et al.. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club.  Gut. 2005;  54 718-725
• 121 Lin R S, Lee F Y, Lee S D et al.. Endotoxaemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation.  J Hepatol. 1995;  22 165-172
• 122 Chan C C, Hwang S J, Lee F Y et al.. Prognostic value of plasma endotoxin levels in patients with cirrhosis.  Scand J Gastroenterol. 1997;  32 942-946
• 123 Szabo G, Romics J L, Frendl G. Liver in sepsis and systemic inflammatory response syndrome.  Clin Liver Dis. 2002;  6 1045-1066
• 124 Ramirez M J, Ibanez A, Navasa M et al.. High density lipoproteins reduce the effect of endotoxin on cytokine production and systemic hemodynamics in cirrhotic rats with ascites.  J Hepatol. 2004;  40 424-430
• 125 Ottesen L H, Harry D, Frost M et al.. Increased formation of S-nitrothiols and nitrotyrosine in cirrhotic rats during endotoxaemia.  Free Radic Biol Med. 2001;  31 790-798
• 126 Deviere J, Content J, Denys C et al.. Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis.  Hepatology. 1990;  11 628-634
• 127 Byl B, Roucloux I, Crusiaux A et al.. Tumor necrosis factor a and interleukin 6 plasma levels in infected cirrhotic patients.  Gastroenterology. 1993;  104 1492-1497
• 128 Heller J, Sogni P, Barrière E et al.. Effects of lipopolysaccharide on TNF-alpha production, hepatic NOS2 activity, and hepatic toxicity in rats with cirrhosis.  J Hepatol. 2000;  33 376-381
• 129 Antoniades C G, Wendon J, Vergani D. Paralysed monocytes in acute on chronic liver disease.  J Hepatol. 2005;  42 163-165
• 130 Tschaikowsky K, Hedwig-Geissing M, Schiele A et al.. Coincidence of pro- and anti-inflammatory responses in the early phase of severe sepsis: longitudinal study of mononuclear histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in septic and postoperative patients.  Crit Care Med. 2002;  30 1015-1023
• 131 Le Tulzo Y, Pangault C, Amiot L et al.. Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock.  Am J Respir Crit Care Med. 2004;  169 1144-1151
• 132 Wasmuth H E, Kunz D, Yagmur E et al.. Patients with acute on chronic liver failure display “sepsis-like” immune paralysis.  J Hepatol. 2005;  42 195-201
• 133 Lin C Y, Tsai I F, Ho Y P et al.. Endotoxemia contributes to the immune paralysis in patients with cirrhosis.  J Hepatol. 2007;  46 816-826
• 134 Fumeaux T, Pugin J. Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock.  Am J Respir Crit Care Med. 2002;  166 1475-1482
• 135 Arabi Y, Ahmed Q A, Haddad S et al.. Outcome predictors of cirrhosis patients admitted to the intensive care unit.  Eur J Gastroenterol Hepatol. 2004;  16 333-339
• 136 Moreau R, Hadengue A, Soupison T et al.. Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome.  Crit Care Med. 1992;  20 746-750
• 137 Follo A, Llovet J M, Navasa M et al.. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis.  Hepatology. 1994;  20 1495-1501
• 138 Salerno F, Gerbes A, Ginès P et al.. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis.  Gut. 2007;  56 1310-1318
• 139 Lee S S. Cardiac dysfunction in spontaneous bacterial peritonitis: a manifestation of cirrhotic cardiomyopathy?.  Hepatology. 2003;  38 1089-1091
• 140 Navasa M, Follo A, Filella X et al.. Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: relationship with the development of renal failure and mortality.  Hepatology. 1998;  27 1227-1232
• 141 Such J, Hillebrand D J, Guarner C et al.. Nitric oxide in ascitic fluid is an independent predictor of the development of renal impairment in patients with cirrhosis and spontaneous bacterial peritonitis.  Eur J Gastroenterol Hepatol. 2004;  16 571-577
• 142 Terra C, Guevara M, Torre A et al.. Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score.  Gastroenterology. 2005;  129 1944-1953
• 143 Fasolato S, Angeli P, Dallagnese L et al.. Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features.  Hepatology. 2007;  45 223-229
• 144 du Cheyron D, Bouchet B, Parienti J J et al.. The attributable mortality of acute renal failure in critically ill patients with liver cirrhosis.  Intensive Care Med. 2005;  31 1693-1699
• 145 Vaquero J, Polson J, Chung C et al.. Infection and the progression of hepatic encephalopathy in acute liver failure.  Gastroenterology. 2003;  125 755-764
• 146 Shawcross D L, Davies N A, Williams R et al.. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis.  J Hepatol. 2004;  40 247-254
• 147 Blei A T. Infection, inflammation and hepatic encephalopathy, synergism redefined.  J Hepatol. 2004;  40 327-330
• 148 Wright G, Davies N A, Shawcross D L et al.. Endotoxemia produces coma and brain swelling in bile duct ligated rats.  Hepatology. 2007;  45 1517-1526
• 149 Plessier A, Denninger M H, Consigny Y et al.. Coagulation disorders in patients with cirrhosis and severe sepsis.  Liver Int. 2003;  23 440-448
• 150 Amitrano L, Guardascione M A, Brancaccio V, Balzano A. Coagulation disorders in liver disease.  Semin Liver Dis. 2002;  22 83-96
• 151 Zambruni A, Thalheimer U, Coppell J et al.. Endogenous heparin-like activity detected by anti-Xa assays in cirrhotic and non-cirrhotic patients.  Scand J Gastroenterol. 2004;  39 830-836
• 152 Goulis J, Patch D, Burroughs A K. Bacterial infection in the pathogenesis of variceal bleeding.  Lancet. 1999;  353 139-142
• 153 Hou M C, Lin H C, Lee F Y et al.. Prophylactic antibiotic prevents rebleeding in patients with acute gastroesophageal variceal bleeding following endoscopic treatment: a randomized trial.  Hepatology. 2003;  38 292A
• 154 Bernard G R, Artigas A, Brigham K et al.. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.  Am J Respir Crit Care Med. 1994;  149 818-824
• 155 Monchi M, Bellenfant F, Cariou A et al.. Early predictive factors of survival in the acute respiratory distress syndrome: a multivariate analysis.  Am J Respir Crit Care Med. 1998;  158 1076-1081
• 156 TenHoor T, Mannino D M, Moss M. Risk Factors for ARDS in the United States: analysis of the 1993 National Mortality Followback Study.  Chest. 2001;  119 1179-1184
• 157 Kaplan J E, Saba T M. Platelet removal from the circulation by the liver and spleen.  Am J Physiol. 1978;  235 H314-H320
• 158 Matuschak G M. Lung-liver interactions in sepsis and multiple organ failure syndrome.  Clin Chest Med. 1996;  17 83-98
• 159 Aggarwal A, Ong J P, Younossi Z M et al.. Predictors of mortality and resource utilization in cirrhotic patients admitted to the medical ICU.  Chest. 2001;  119 1489-1497
• 160 Kamath P S, Wiesner R H, Malinchoc M et al.. A model to predict survival in patients with end-stage liver disease.  Hepatology. 2001;  33 464-470
• 161 Pugh R N, Murray-Lyon I M, Dawson J L et al.. Transection of the oesophagus for bleeding oesophageal varices.  Br J Surg. 1973;  60 646-649
• 162 Knaus W A, Draper E A, Wagner D P et al.. APACHE II: a severity of disease classification system.  Crit Care Med. 1985;  13 818-829
• 163 Knaus W A, Wagner D P, Draper E A et al.. The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults.  Chest. 1991;  100 1619-1639
• 164 Knaus W A, Draper E A, Wagner D P et al.. Prognosis in acute organ-system failure.  Ann Surg. 1985;  202 685-693
• 165 Vincent J L, Moreno R, Takala J et al.. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study.  Crit Care Med. 1998;  26 1793-1800
• 166 Hung P D, Sterling R K. Predicting outcome of critically ill patients with cirrhosis admitted to the intensive care unit.  J Clin Gastroenterol. 2003;  37 203-205
• 167 Cholongitas E, Senzolo M, Patch D et al.. Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.  Aliment Pharmacol Ther. 2006;  24 453-464
• 168 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;  23 883-893
• 169 Tsai M H, Chen Y C, Ho Y P et al.. Organ system failure scoring system can predict hospital mortality in critically ill cirrhotic patients.  J Clin Gastroenterol. 2003;  37 251-257
• 170 Rothwell P M, Udwadia Z F, Lawler P G. Cortisol response to corticotropin and survival in septic shock.  Lancet. 1991;  337 582-583
• 171 Bollaert P E, Fieux F, Charpentier C, Levy B. Baseline cortisol levels, cortisol response to corticotropin, and prognosis in late septic shock.  Shock. 2003;  19 13-15
• 172 Annane D, Bellissant E, Sebille V et al.. Impaired pressor sensitivity to norepinephrine in septic shock patients with and without impaired adrenal function reserve.  Br J Clin Pharmacol. 1998;  46 589-597
• 173 Annane D, Bellissant E, Bollaert P E et al.. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis.  BMJ. 2004;  329 480-489
• 174 Minneci P C, Deans K J, Banks S M et al.. Meta-analysis: the effects of steroids on survival and shock during sepsis depends on the dose.  Ann Intern Med. 2004;  141 47-56
• 175 Tsai M H, Peng Y S, Chen Y C et al.. Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock.  Hepatology. 2006;  43 673-681
• 176 Cochrane Injuries Group . Human albumin administration in critically ill patients: systematic review of randomized controlled trials.  BMJ. 1998;  317 235-240
• 177 Wilkes M M, Navickis R J. Patient survival after human albumin administration: a meta-analysis of randomized, controlled trials.  Ann Intern Med. 2001;  135 149-164
• 178 Finfer S, Bellomo R, Boyce N et al.. A comparison of albumin and saline for fluid resuscitation in the intensive care unit.  N Engl J Med. 2004;  350 2247-2256
• 179 Vincent J L, Sakr Y, Reinhart K et al.. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study.  Crit Care. 2005;  9 R745-R754
• 180 Moreau R, Durand F, Poynard T et al.. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.  Gastroenterology. 2002;  122 923-930
• 181 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;  36 941-948
• 182 Gluud L L, Kjaer M S, Christensen E. Terlipressin for hepatorenal syndrome.  Cochrane Database Syst Rev. 2006;  (4) CD005162
• 183 Sanyal A, Boyer T, Garcia-Tsao G et al.. A prospective, randomized, double-blind placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome (HRS).  Hepatology. 2006;  44 694A
• 184 Angeli P, Volpin R, Gerunda G et al.. Reversal of type 1 hepatorenal syndrome (HRS) with the combined administration of midodrine and octreotide.  Hepatology. 1999;  29 1690-1697
• 185 Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome.  Hepatology. 2004;  40 55-64
• 186 Moreau R, Barriére E, Tazi K A et al.. Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis.  Hepatology. 2002;  36 1070-1078
• 187 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
• 188 Uriu K, Osajima A, Hiroshige K et al.. Endotoxin removal by direct hemoperfusion with an adsorbent column using polymyxin B-immobilized fiber ameliorates systemic circulatory disturbance in patients with septic shock.  Am J Kidney Dis. 2002;  39 937-947
• 189 Donati G, Piscaglia F, Coli L et al.. Acute systemic, splanchnic and renal hemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end-stage cirrhosis.  Aliment Pharmacol Ther. 2007;  26 717-726
• 190 Khuroo M S, Khuroo M S, Farahat K L. Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: a meta-analysis.  Liver Transpl. 2004;  10 1099-1106
• 191 Rittler P, Ketscher C, Inthorn D et al.. Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction: preliminary results.  Liver Int. 2004;  24 136-141