Intensive Management of Hepatic Failure

Mary E. Rinella; Arun Sanyal

doi:10.1055/s-2006-945528

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2006; 27(3): 241-261
DOI: 10.1055/s-2006-945528

Intensive Management of Hepatic Failure

Mary E. Rinella¹ , Arun Sanyal²

¹Division of Hepatology, Northwestern University, Chicago, Illinois
²Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia

Abstract

ABSTRACT

A substantial number of patients with liver failure are admitted to the intensive care unit; thus a thorough understanding of the prevention and treatment of complications in such patients is imperative. The management of liver failure is demanding and often involves the combined efforts of many specialists. Critically ill patients with hepatic failure encompass a broad spectrum of disease, ranging from acute liver failure in a patient with no prior history of liver disease, to acute on chronic liver failure. The initial assessment and management of acute liver failure are reviewed with an emphasis on the prevention and treatment of brain edema in the pretransplant setting. The current treatment of complications resulting from decompensated chronic liver disease such as portal hypertensive bleeding; infection, renal failure, and hepatic encephalopathy are then discussed.

KEYWORDS

Liver failure - cerebral edema - portal hypertension - management

Full Text

References

REFERENCES

1 Trey C, Lipworth L, Davidson C S. Halothane and liver damage. N Engl J Med. 1969; 280 562-563
2 Trey C, Davidson C S. The management of fulminant hepatic failure. Prog Liver Dis. 1970; 3 282-298
3 Bernal W, Wendon J. Liver transplantation in adults with acute liver failure. J Hepatol. 2004; 40 192-197
4 Blei A T. Medical therapy of brain edema in fulminant hepatic failure. Hepatology. 2000; 32 666-669
5 Mas A, Rodes J. Fulminant hepatic failure. Lancet. 1997; 349 1081-1085
6 Larsen F S, Wendon J. Brain edema in liver failure: basic physiologic principles and management. Liver Transpl. 2002; 8 983-989
7 O'Grady J G, Alexander G J, Hayllar K M, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989; 97 439-446
8 Izumi S, Langley P G, Wendon J et al.. Coagulation factor V levels as a prognostic indicator in fulminant hepatic failure. Hepatology. 1996; 23 1507-1511
9 Pereira L M, Langley P G, Hayllar K M, Tredger J M, Williams R. Coagulation factor V and VIII/V ratio as predictors of outcome in paracetamol induced fulminant hepatic failure: relation to other prognostic indicators. Gut. 1992; 33 98-102
10 Lee W M. Acute liver failure in the United States. Semin Liver Dis. 2003; 23 217-226
11 Seeff L B, Cuccherini B A, Zimmerman H J, Adler E, Benjamin S B. Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med. 1986; 104 399-404
12 Ostapowicz G, Fontana R J, Schiodt F V et al.. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002; 137 947-954
13 Makin A J, Wendon J, Williams R. A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987-1993). Gastroenterology. 1995; 109 1907-1916
14 Zimmerman H J, Maddrey W C. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatology. 1995; 22 767-773
15 Schiodt F V, Rochling F A, Casey D L, Lee W M. Acetaminophen toxicity in an urban county hospital. N Engl J Med. 1997; 337 1112-1117
16 McClain C J, Kromhout J P, Peterson F J, Holtzman J L. Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA. 1980; 244 251-253
17 Murphy R, Swartz R, Watkins P B. Severe acetaminophen toxicity in a patient receiving isoniazid. Ann Intern Med. 1990; 113 799-800
18 Prescott L F, Critchley J A. The treatment of acetaminophen poisoning. Annu Rev Pharmacol Toxicol. 1983; 23 87-101
19 Lee W M. Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology. 2004; 40 6-9
20 Harrison P M, Keays R, Bray G P, Alexander G J, Williams R. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet. 1990; 335 1572-1573
21 Donaldson B W, Gopinath R, Wanless I R et al.. The role of transjugular liver biopsy in fulminant liver failure: relation to other prognostic indicators. Hepatology. 1993; 18 1370-1376
22 Chung P Y, Sitrin M D, Te H S. Serum phosphorus levels predict clinical outcome in fulminant hepatic failure. Liver Transpl. 2003; 9 248-253
23 Schmidt L E, Dalhoff K. Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury. Hepatology. 2005; 41 26-31
24 Baquerizo A, Anselmo D, Shackleton C et al.. Phosphorus as an early predictive factor in patients with acute liver failure. Transplantation. 2003; 75 2007-2014
25 Shami V M, Caldwell S H, Hespenheide E E, Arseneau K O, Bickston S J, Macik B G. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl. 2003; 9 138-143
26 Bernal W. Intensive care support therapy. Liver Transpl. 2003; 9(suppl 9) S15-S17
27 Vaquero J, Chung C, Cahill M E, Blei A T. Pathogenesis of hepatic encephalopathy in acute liver failure. Semin Liver Dis. 2003; 23 259-269
28 Vaquero J, Blei A T. Etiology and management of fulminant hepatic failure. Curr Gastroenterol Rep. 2003; 5 39-47
29 Wijdicks E F, Nyberg S L. Propofol to control intracranial pressure in fulminant hepatic failure. Transplant Proc. 2002; 34 1220-1222
30 Steinberg K P. Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit. Crit Care Med. 2002; 30(Suppl 6) S362-S364
31 Jalan R. Intracranial hypertension in acute liver failure: pathophysiological basis of rational management. Semin Liver Dis. 2003; 23 271-282
32 Ellis A, Wendon J. Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: pathophysiology and management. Semin Liver Dis. 1996; 16 379-388
33 Trewby P N, Williams R. Pathophysiology of hypotension in patients with fulminant hepatic failure. Gut. 1977; 18 1021-1026
34 Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000; 32(4 Pt 1) 734-739
35 Bouachour G, Tirot P, Varache N, Gouello J P, Harry P, Alquier P. Hemodynamic changes in acute adrenal insufficiency. Intensive Care Med. 1994; 20 138-141
36 Bollaert P E, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998; 26 645-650
37 McCashland T M, Shaw Jr B W, Tape E. The American experience with transplantation for acute liver failure. Semin Liver Dis. 1996; 16 427-433
38 Davies M H, Mutimer D, Lowes J, Elias E, Neuberger J. Recovery despite impaired cerebral perfusion in fulminant hepatic failure. Lancet. 1994; 343 1329-1330
39 Wyke R J, Yousif-Kadaru A G, Rajkovic I A, Eddleston A L, Williams R. Serum stimulatory activity and polymorphonuclear leucocyte movement in patients with fulminant hepatic failure. Clin Exp Immunol. 1982; 50 442-449
40 Wyke R J, Rajkovic I A, Eddleston A L, Williams R. Defective opsonisation and complement deficiency in serum from patients with fulminant hepatic failure. Gut. 1980; 21 643-649
41 Altin M, Hughes R D, Williams R. Neutrophil adherence during hemoperfusion in fulminant hepatic failure. Int J Artif Organs. 1982; 5 315-317
42 Clapperton M, Rolando N, Sandoval L, Davies E, Williams R. Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure. Eur J Clin Invest. 1997; 27 164-168
43 Rolando N, Harvey F, Brahm J et al.. Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients. Hepatology. 1990; 11 49-53
44 Rolando N, Philpott-Howard J, Williams R. Bacterial and fungal infection in acute liver failure. Semin Liver Dis. 1996; 16 389-402
45 Wade J, Rolando N, Philpott-Howard J, Wendon J. Timing and aetiology of bacterial infections in a liver intensive care unit. J Hosp Infect. 2003; 53 144-146
46 Rolando N, Gimson A, Wade J, Philpott-Howard J, Casewell M, Williams R. Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure. Hepatology. 1993; 17 196-201
47 Salmeron J M, Tito L, Rimola A et al.. Selective intestinal decontamination in the prevention of bacterial infection in patients with acute liver failure. J Hepatol. 1992; 14 280-285
48 Rolando N, Wade J J, Stangou A et al.. Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure. Liver Transpl Surg. 1996; 2 8-13
49 Vaquero J, Polson J, Chung C et al.. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology. 2003; 125 755-764
50 Billiau A, Vandekerckhove F. Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock. Eur J Clin Invest. 1991; 21 559-573
51 Jalan R, Pollok A, Shah S H, Madhavan K, Simpson K J. Liver derived pro-inflammatory cytokines may be important in producing intracranial hypertension in acute liver failure. J Hepatol. 2002; 37 536-538
52 Bihari D J, Gimson A E, Williams R. Cardiovascular, pulmonary and renal complications of fulminant hepatic failure. Semin Liver Dis. 1986; 6 119-128
53 Briegel J, Forst H, Haller M et al.. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999; 27 723-732
54 Harry R, Auzinger G, Wendon J. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology. 2002; 36 395-402
55 Davenport A, Will E J, Davison A M et al.. Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy. Nephron. 1989; 53 142-146
56 Davenport A, Will E J, Davidson A M. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med. 1993; 21 328-338
57 Davenport A, Will E J, Davison A M. Continuous vs. intermittent forms of haemofiltration and/or dialysis in the management of acute renal failure in patients with defective cerebral autoregulation at risk of cerebral oedema. Contrib Nephrol. 1991; 93 225-233
58 O'Grady J G. Paracetamol hepatotoxicity: how to prevent. J R Soc Med. 1997; 90 368-370
59 Blei A T. Hypothermia for hypertension. Lancet. 1999; (9195) 2082
60 Clemmesen J O, Larsen F S, Kondrup J, Hansen B A, Ott P. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999; 29 648-653
61 Strauss G I, Knudsen G M, Kondrup J, Moller K, Larsen F S. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure. Gastroenterology. 2001; 121 1109-1119
62 Strauss G I, Christiansen M, Moller K, Clemmesen J O, Larsen F S, Knudsen G M. S-100b and neuron-specific enolase in patients with fulminant hepatic failure. Liver Transpl. 2001; 7 964-970
63 Keays R T, Alexander G J, Williams R. The safety and value of extradural intracranial pressure monitors in fulminant hepatic failure. J Hepatol. 1993; 18 205-209
64 Lidofsky S D, Bass N M, Prager M C et al.. Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure. Hepatology. 1992; 16 1-7
65 Donovan J P, Shaw Jr B W, Langnas A N, Sorrell M F. Brain water and acute liver failure: the emerging role of intracranial pressure monitoring. Hepatology. 1992; 16 267-268
66 Larsen F S, Knudsen G M, Hansen B A. Pathophysiological changes in cerebral circulation, oxidative metabolism and blood-brain barrier in patients with acute liver failure: tailored cerebral oxygen utilization. J Hepatol. 1997; 27 231-238
67 Toftengi F, Larsen F S. Management of patients with fulminant hepatic failure and brain edema. Metab Brain Dis. 2004; 19 207-214
68 Blei A T, Olafsson S, Webster S, Levy R. Complications of intracranial pressure monitoring in fulminant hepatic failure. Lancet. 1993; 341 157-158
69 Vaquero J, Blei A, Fontana R J et al.. Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transpl. 2005; 12 1581-1589
70 Cordoba J, Blei A T. Cerebral edema and intracranial pressure monitoring. Liver Transpl Surg. 1995; 1 187-194
71 Caldwell S H, Chang C, Macik B G. Recombinant activated factor VII (rFVIIa) as a hemostatic agent in liver disease: a break from convention in need of controlled trials. Hepatology. 2004; 39 592-598
72 Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology. 2004; 39 464-470
73 Clemmesen J O, Kondrup J, Nielsen L B, Larsen F S, Ott P. Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure. Am J Gastroenterol. 2001; 96 1217-1223
74 Awad S S, Swaniker F, Magee J, Punch J, Bartlett R H. Results of a phase I trial evaluating a liver support device utilizing albumin dialysis. Surgery. 2001; 130 354-362
75 Rose C, Michalak A, Rao K V, Quack G, Kircheis G, Butterworth R F. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology. 1999; 30 636-640
76 Canalese J, Gimson A E, Davis C, Mellon P J, Davis M, Williams R. Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure. Gut. 1982; 23 625-629
77 Ede R J, Gimson A E, Bihari D, Williams R. Controlled hyperventilation in the prevention of cerebral oedema in fulminant hepatic failure. J Hepatol. 1986; 2 43-51
78 Strauss G I, Moller K, Holm S, Sperling B, Knudsen G M, Larsen F S. Transcranial Doppler sonography and internal jugular bulb saturation during hyperventilation in patients with fulminant hepatic failure. Liver Transpl. 2001; 7 352-358
79 Strauss G, Hansen B A, Knudsen G M, Larsen F S. Hyperventilation restores cerebral blood flow autoregulation in patients with acute liver failure. J Hepatol. 1998; 28 199-203
80 Jensen K, Ohrstrom J, Cold G E, Astrup J. Indomethacin (Confortid) in severe head injury and elevated intracranial pressure (ICP). Acta Neurochir Suppl (Wien). 1992; 55 47-48
81 Chung C, Gottstein J, Blei A T. Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis. Hepatology. 2001; 34 249-254
82 Tofteng F, Larsen F S. The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure. J Cereb Blood Flow Metab. 2004; 24 798-804
83 Forbes A, Alexander G J, O'Grady J G et al.. Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure. Hepatology. 1989; 10 306-310
84 Peignoux M, Bernuau J, Benhamou J P. Total hepatectomy and hepatic vascular exclusion in the rat: a comparison, with special reference to the influence of body temperature. Clin Sci (Lond). 1982; 62 273-277
85 Eguchi S, Kamlot A, Ljubimova J et al.. Fulminant hepatic failure in rats: survival and effect on blood chemistry and liver regeneration. Hepatology. 1996; 24 1452-1459
86 Jalan R, Damink S W, Deutz N E, Lee A, Hayes P C. Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet. 1999; 354 1164-1168
87 Jalan R, Olde Damink S W, Deutz N E et al.. Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver transplantation for acute liver failure. Transplantation. 2003; 75 2034-2039
88 Jalan R, Olde Damink S W, Deutz N E, Hayes P C, Lee A. Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology. 2004; 127 1338-1346
89 Bernuau J. Acute liver failure: avoidance of deleterious cofactors and early specific medical therapy for the liver are better than late intensive care for the brain. J Hepatol. 2004; 41 152-155
90 Munoz S J. Hypothermia may impair hepatic regeneration in acute liver failure. Gastroenterology. 2005; 128 1143-1144 author reply 1144-1145
91 Rozga J, Williams F, Ro M S et al.. Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells. Hepatology. 1993; 17 258-265
92 Sussman N L, Kelly J H. Extracorporeal liver support: cell-based therapy for the failing liver. Am J Kidney Dis. 1997; 30(5, Suppl 4) S66-S71
93 Demetriou A A, Brown Jr R S, Busuttil R W et al.. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg. 2004; 239 660-667 discussion 667-670
94 Ellis A J, Hughes R D, Wendon J A et al.. Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology. 1996; 24 1446-1451
95 Jalan R, Sen S, Williams R. Prospects for extracorporeal liver support. Gut. 2004; 53 890-898
96 Stange J, Mitzner S, Ramlow W, Gliesche T, Hickstein H, Schmidt R. A new procedure for the removal of protein bound drugs and toxins. ASAIO J. 1993; 39 M621-M625
97 Stange J, Ramlow W, Mitzner S, Schmidt R, Klinkmann H. Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins. Artif Organs. 1993; 17 809-813
98 Stange J, Mitzner S R, Klammt S et al.. Liver support by extracorporeal blood purification: a clinical observation. Liver Transpl. 2000; 6 603-613
99 Lutkes P, Lutz J, Loock J et al.. Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation. Kidney Int Suppl. 1999; (72) S71-S74
100 Mitzner S R, 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; 6 277-286
101 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
102 Sen S SC, Williams R. Artificial liver support: overview of registry and controlled trials. In: Arroyo VFX, Garcia-Pagan JC Progress in the Treatment of Liver Diseases. Barcelona; Ars Medica 2003: 429-435
103 Singh N, Gayowski T, Wagener M M, Marino I R. Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality. J Gastroenterol. 1998; 33 73-79
104 Kress J P, Rubin A, Pohlman A S, Hall J B. Outcomes of critically ill patients denied consideration for liver transplantation. Am J Respir Crit Care Med. 2000; 162(2 Pt 1) 418-423
105 Zimmerman J E, Wagner D P, Seneff M G, Becker R B, Sun X, Knaus W A. Intensive care unit admissions with cirrhosis: risk-stratifying patient groups and predicting individual survival. Hepatology. 1996; 23 1393-1401
106 Aggarwal A, Ong J P, Younossi Z M, Nelson D R, Hoffman-Hogg L, Arroliga A C. Predictors of mortality and resource utilization in cirrhotic patients admitted to the medical ICU. Chest. 2001; 119 1489-1497
107 Schrier R W, Arroyo V, Bernardi M, Epstein M, Henriksen J H, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988; 8 1151-1157
108 Gores G J, Wiesner R H, Dickson E R, Zinsmeister A R, Jorgensen R A, Langworthy A. Prospective evaluation of esophageal varices in primary biliary cirrhosis: development, natural history, and influence on survival. Gastroenterology. 1989; 96 1552-1559
109 Groszmann R J, Bosch J, Grace N D et al.. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology. 1990; 99 1401-1407
110 The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: a prospective multicenter study. N Engl J Med. 1988; 319 983-989
111 Mahl T C, Groszmann R J. Pathophysiology of portal hypertension and variceal bleeding. Surg Clin North Am. 1990; 70 251-266
112 Garcia-Tsao G, Groszmann R J, Fisher R L, Conn H O, Atterbury C E, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology. 1985; 5 419-424
113 Vorobioff J, Groszmann R J, Picabea E et al.. Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: a 10-year prospective study. Gastroenterology. 1996; 111 701-709
114 Moitinho E, Escorsell A, Bandi J C et al.. Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology. 1999; 117 626-631
115 Grace N D, Groszmann R J, Garcia-Tsao G et al.. Portal hypertension and variceal bleeding: an AASLD single topic symposium. Hepatology. 1998; 28 868-880
116 Rossle M. Prevention of rebleeding from oesophageal-gastric varices. Eur J Gastroenterol Hepatol. 2001; 13 343-348
117 Escorsell A, Bordas J M, Castaneda B et al.. Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension. Hepatology. 2000; 31 1061-1067
118 Chalasani N, Kahi C, Francois F et al.. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol. 2003; 98 653-659
119 Benoit J N, Womack W A, Korthuis R J, Wilborn W H, Granger D N. Chronic portal hypertension: effects on gastrointestinal blood flow distribution. Am J Physiol. 1986; 250(4 Pt 1) G535-G539
120 Graham D Y, Smith J L. The course of patients after variceal hemorrhage. Gastroenterology. 1981; 80 800-809
121 Kravetz D, Bosch J, Arderiu M, Pilar Pizcueta M, Rodes J. Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting. Hepatology. 1989; 9 808-814
122 Kruskall M S, Mintz P D, Bergin J J et al.. Transfusion therapy in emergency medicine. Ann Emerg Med. 1988; 17 327-335
123 D'Amico G, De Franchis R. Upper digestive bleeding in cirrhosis: posttherapeutic outcome and prognostic indicators. Hepatology. 2003; 38 599-612
124 El-Serag H B, Everhart J E. Improved survival after variceal hemorrhage over an 11-year period in the Department of Veterans Affairs. Am J Gastroenterol. 2000; 95 3566-3573
125 Ioannou G N, Doust J, Rockey D C. Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther. 2003; 17 53-64
126 Escorsell A, Ruiz del Arbol L, Planas R et al.. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology. 2000; 32 471-476
127 Watanabe K, Kimura K, Matsutani S, Ohto M, Okuda K. Portal hemodynamics in patients with gastric varices: a study in 230 patients with esophageal and/or gastric varices using portal vein catheterization. Gastroenterology. 1988; 95 434-440
128 Sarin S K, Lahoti D, Saxena S P, Murthy N S, Makwana U K. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology. 1992; 16 1343-1349
129 Kim T, Shijo H, Kokawa H et al.. Risk factors for hemorrhage from gastric fundal varices. Hepatology. 1997; 25 307-312
130 Ohnishi K, Sato S, Saito M et al.. Clinical and portal hemodynamic features in cirrhotic patients having a large spontaneous splenorenal and/or gastrorenal shunt. Am J Gastroenterol. 1986; 81 450-455
131 Rinella M E, Shah D, Vogelzang R L, Blei A T, Flamm S L. Fundal variceal bleeding after correction of portal hypertension in patients with cirrhosis. Gastrointest Endosc. 2003; 58 122-127
132 Thakeb F, Salem S A, Abdallah M, el Batanouny M. Endoscopic diagnosis of gastric varices. Endoscopy. 1994; 26 287-291
133 Sarin S K, Govil A, Jain A K et al.. Prospective randomized trial of endoscopic sclerotherapy versus variceal band ligation for esophageal varices: influence on gastropathy, gastric varices and variceal recurrence. J Hepatol. 1997; 26 826-832
134 Sarin S K, Jain A K, Jain M, Gupta R. A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices. Am J Gastroenterol. 2002; 97 1010-1015
135 Lo G H, Lai K H, Cheng J S, Chen M H, Chiang H T. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology. 2001; 33 1060-1064
136 Gallet B, Zemour G, Saudemont J P, Renard P, Hillion M L, Hiltgen M. Echocardiographic demonstration of intracardiac glue after endoscopic obturation of gastroesophageal varices. J Am Soc Echocardiogr. 1995; 8(5 Pt 1) 759-761
137 Rickman O B, Utz J P, Aughenbaugh G L, Gostout C J. Pulmonary embolization of 2-octyl cyanoacrylate after endoscopic injection therapy for gastric variceal bleeding. Mayo Clin Proc. 2004; 79 1455-1458
138 See A, Florent C, Lamy P, Levy V G, Bouvry M. Cerebrovascular accidents after endoscopic obturation of esophageal varices with isobutyl-2-cyanoacrylate in 2 patients. Gastroenterol Clin Biol. 1986; 10 604-607
139 Yang W L, Tripathi D, Therapondos G, Todd A, Hayes P C. Endoscopic use of human thrombin in bleeding gastric varices. Am J Gastroenterol. 2002; 97 1381-1385
140 Yoshida T, Harada T, Shigemitsu T, Takeo Y, Miyazaki S, Okita K. Endoscopic management of gastric varices using a detachable snare and simultaneous endoscopic sclerotherapy and O-ring ligation. J Gastroenterol Hepatol. 1999; 14 730-735
141 Yoshida T, Hayashi N, Suzumi N et al.. Endoscopic ligation of gastric varices using a detachable snare. Endoscopy. 1994; 26 502-505
142 Kanagawa H, Mima S, Kouyama H, Gotoh K, Uchida T, Okuda K. Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol. 1996; 11 51-58
143 Fukuda T, Hirota S, Sugimura K. Long-term results of balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy. J Vasc Interv Radiol. 2001; 12 327-336
144 Sanyal A J. The use and misuse of transjugular intrahepatic portasystemic shunts. Curr Gastroenterol Rep. 2000; 2 61-71
145 Chau T N, Patch D, Chan Y W, Nagral A, Dick R, Burroughs A K. “Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding. Gastroenterology. 1998; 114 981-987
146 Henderson J M. Role of distal splenorenal shunt for long-term management of variceal bleeding. World J Surg. 1994; 18 205-210
147 Merli M, Salerno F, Riggio O et al.. Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: a randomized multicenter trial. Gruppo Italiano Studio Trends Pharmacol Sci (G.I.S.T.) Hepatology. 1998; 27 48-53
148 Zhou J H, Liu C Y, Zhang R H, Wang H R, Liu K J. Effects of octreotide on gallbladder pressure and myoelectric activity of Oddi sphincter in rabbits. World J Gastroenterol. 1998; 4 238-241
149 Garcia N, Sanyal A J. Portal hypertensive gastropathy and gastric antral vascular ectasia. Curr Treat Options Gastroenterol. 2001; 4 163-171
150 Kamath P S, Lacerda M, Ahlquist D A, McKusick M A, Andrews J C, Nagorney D A. Gastric mucosal responses to intrahepatic portosystemic shunting in patients with cirrhosis. Gastroenterology. 2000; 118 905-911
151 Bosch J, Thabut D, Bendtsen F et al.. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology. 2004; 127 1123-1130
152 Jenkins S A, Shields R, Davies M et al.. A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage. Gut. 1997; 41 526-533
153 Escorsell A, Bandi J C, Andreu V et al.. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology. 2001; 120 161-169
154 Besson I, Ingrand P, Person B et al.. Sclerotherapy with or without octreotide for acute variceal bleeding. N Engl J Med. 1995; 333 555-560
155 Sung J J, Chung S C, Yung M Y et al.. Prospective randomised study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation. Lancet. 1995; 346 1666-1669
156 Conn H O, Ramsby G R, Storer E H et al.. Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial. Gastroenterology. 1975; 68 211-221
157 Bosch J, Groszmann R J, Garcia-Pagan J C et al.. Association of transdermal nitroglycerin to vasopressin infusion in the treatment of variceal hemorrhage: a placebo-controlled clinical trial. Hepatology. 1989; 10 962-968
158 Gimson A E, Westaby D, Hegarty J, Watson A, Williams R. A randomized trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal hemorrhage. Hepatology. 1986; 6 410-413
159 Soderlund C, Magnusson I, Torngren S, Lundell L. Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices: a double-blind, randomized, placebo-controlled trial. Scand J Gastroenterol. 1990; 25 622-630
160 Garcia-Compean D, Blanc P, Bories J M et al.. Treatment of active gastroesophageal variceal bleeding with terlipressin or hemostatic balloon in patients with cirrhosis: a randomized controlled trial. Arch Med Res. 1997; 28 241-245
161 Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: a meta-analysis. Ann Intern Med. 1995; 123 280-287
162 Stiegmann G V, Goff J S, Michaletz-Onody P A et al.. Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med. 1992; 326 1527-1532
163 Sarin S K, Lamba G S, Kumar M, Misra A, Murthy N S. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med. 1999; 340 988-993
164 Sarin S K, Guptan R K, Jain A K, Sundaram K R. A randomized controlled trial of endoscopic variceal band ligation for primary prophylaxis of variceal bleeding. Eur J Gastroenterol Hepatol. 1996; 8 337-342
165 Lay C S, Tsai Y T, Teg C Y et al.. Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices. Hepatology. 1997; 25 1346-1350
166 Harry R, Wendon J. Management of variceal bleeding. Curr Opin Crit Care. 2002; 8 164-170
167 Chojkier M, Conn H O. Esophageal tamponade in the treatment of bleeding varices: a decadel progress report. Dig Dis Sci. 1980; 25 267-272
168 Sanyal A J, Freedman A M, Luketic V A et al.. The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts. Gastroenterology. 1997; 112 889-898
169 Sanyal A J, Freedman A M, Luketic V A et al.. Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy. Gastroenterology. 1996; 111 138-146
170 Bureau C, Garcia-Pagan J C, Otal P et al.. Improved clinical outcome using polytetrafluoroethylene-coated stents for Trends Pharmacol Sci: results of a randomized study. Gastroenterology. 2004; 126 469-475
171 Rossi P, Salvatori F M, Fanelli F et al.. Polytetrafluoroethylene-covered nitinol stent-graft for transjugular intrahepatic portosystemic shunt creation: 3-year experience. Radiology. 2004; 231 820-830
172 Ockenga J, Kroencke T J, Schuetz T et al.. Covered transjugular intrahepatic portosystemic stents maintain lower portal pressure and require fewer reinterventions than uncovered stents. Scand J Gastroenterol. 2004; 39 994-999
173 Marchesini G, Fabbri A, Bianchi G, Brizi M, Zoli M. Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology. 1996; 23 1084-1092
174 Kjaergard L L, Liu J, Als-Nielsen B, Gluud C. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA. 2003; 289 217-222
175 Blei A T, Cordoba J. Hepatic encephalopathy. Am J Gastroenterol. 2001; 96 1968-1976
176 Madoff D C, Perez-Young I V, Wallace M J, Skolkin M D, Toombs B D. Management of Trends Pharmacol Sci-related refractory hepatic encephalopathy with reduced Wallgraft endoprostheses. J Vasc Interv Radiol. 2003; 14 369-374
177 Kerlan Jr R K, LaBerge J M, Baker E L et al.. Successful reversal of hepatic encephalopathy with intentional occlusion of transjugular intrahepatic portosystemic shunts. J Vasc Interv Radiol. 1995; 6 917-921
178 Shioyama Y, Matsueda K, Horihata K et al.. Post-Trends Pharmacol Sci hepatic encephalopathy treated by occlusion balloon-assisted retrograde embolization of a coexisting spontaneous splenorenal shunt. Cardiovasc Intervent Radiol. 1996; 19 53-55
179 Bernard B, Cadranel J F, Valla D, Escolano S, Jarlier V, Opolon P. Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study. Gastroenterology. 1995; 108 1828-1834
180 Goulis J, Armonis A, Patch D, Sabin C, Greenslade L, Burroughs A K. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage. Hepatology. 1998; 27 1207-1212
181 Soriano G, Guarner C, Tomas A et al.. Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. Gastroenterology. 1992; 103 1267-1272
182 Blaise M, Pateron D, Trinchet J C, Levacher S, Beaugrand M, Pourriat J L. Systemic antibiotic therapy prevents bacterial infection in cirrhotic patients with gastrointestinal hemorrhage. Hepatology. 1994; 20(1 Pt 1) 34-38
183 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
184 Pauwels A, Mostefa-Kara N, Debenes B, Degoutte E, Levy V G. Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection. Hepatology. 1996; 24 802-806
185 Bernard B, Grange J D, Khac E N, 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 1655-1661
186 Toledo C, Salmeron J M, Rimola A et al.. Spontaneous bacterial peritonitis in cirrhosis: predictive factors of infection resolution and survival in patients treated with cefotaxime. Hepatology. 1993; 17 251-257
187 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
188 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 impairment and mortality. Hepatology. 1998; 27 1227-1232
189 Garcia-Tsao G, Albillos A, Barden G E, West A B. Bacterial translocation in acute and chronic portal hypertension. Hepatology. 1993; 17 1081-1085
190 Llovet J M, Bartoli R, March F et al.. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J Hepatol. 1998; 28 307-313
191 Tito L, Rimola A, Gines P, Llach J, Arroyo V, Rodes J. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. Hepatology. 1988; 8 27-31
192 Andreu M, Sola R, Sitges-Serra A et al.. Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with ascites. Gastroenterology. 1993; 104 1133-1138
193 Runyon B A. Low-protein-concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis. Gastroenterology. 1986; 91 1343-1346
194 Conn H O. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome. Ann Intern Med. 1964; 60 568-580
195 Guarner C, Soriano G. Spontaneous bacterial peritonitis. Semin Liver Dis. 1997; 17 203-217
196 McHutchison J, Runyon B A. Spontaneous bacterial peritonitis. In: Surawicz CM, Owen R Gastrointestinal and Hepatic Infections. Philadelphia, PA; WB Saunders 1994: 455-475
197 Runyon B A, Hoefs J C. Culture-negative neutrocytic ascites: a variant of spontaneous bacterial peritonitis. Hepatology. 1984; 4 1209-1211
198 Chu C M, Chang K Y, Liaw Y F. Prevalence and prognostic significance of bacterascites in cirrhosis with ascites. Dig Dis Sci. 1995; 40 561-565
199 Cabrera J, Arroyo V, Ballesta A M et al.. Aminoglycoside nephrotoxicity in cirrhosis: value of urinary beta 2-microglobulin to discriminate functional renal failure from acute tubular damage. Gastroenterology. 1982; 82 97-105
200 Felisart J, Rimola A, Arroyo V et al.. Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections. Hepatology. 1985; 5 457-462
201 Runyon B A, McHutchison J G, Antillon M R, Akriviadis E A, Montano A A. Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis: a randomized controlled study of 100 patients. Gastroenterology. 1991; 100 1737-1742
202 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
203 Fernandez J, Monteagudo J, Bargallo X et al.. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology. 2005; 42 627-634
204 Ochs A, Rossle M, Haag K et al.. The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites. N Engl J Med. 1995; 332 1192-1197
205 Choudhury J, Sanyal A J. Treatment of ascites. Curr Treat Options Gastroenterol. 2003; 6 481-491
206 Luca A, Garcia-Pagan J C, Bosch J et al.. Beneficial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis. Hepatology. 1995; 22 753-758
207 Dagher L, Moore K. The hepatorenal syndrome. Gut. 2001; 49 729-737
208 Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med. 2004; 350 1646-1654
209 Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet. 2003; 362 1819-1827
210 Arroyo V, Gines P, Gerbes A L et al.. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996; 23 164-176
211 Moller S, Bendtsen F, Henriksen J H. Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome. Scand J Gastroenterol. 2005; 40 491-500
212 Laffi G, La Villa G, Gentilini P. Pathogenesis and management of the hepatorenal syndrome. Semin Liver Dis. 1994; 14 71-81
213 Arroyo V, Guevara M, Gines P. Hepatorenal syndrome in cirrhosis: pathogenesis and treatment. Gastroenterology. 2002; 122 1658-1676
214 Maurizio R, Eugenio C, Roberto P R. Results of sclerotherapy for bleeding esophageal varices in patients with schistosomal liver disease: a retrospective study. Hepatogastroenterology. 2000; 47 424-428
215 Ortega R, Gines 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
216 Angeli P, Volpin R, Gerunda G et al.. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology. 1999; 29 1690-1697
217 Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and Trends Pharmacol Sci in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004; 40 55-64
218 Malinchoc M, Kamath P S, Gordon F D, Peine C J, Rank J, ter Borg P C. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000; 31 864-871
219 Wiesner R H, McDiarmid S V, Kamath P S et al.. MELD and PELD: application of survival models to liver allocation. Liver Transpl. 2001; 7 567-580
220 Wiesner R, Edwards E, Freeman R et al.. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003; 124 91-96

Arun SanyalM.D.

Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University

MCV Box 980341, Richmond, VA 23298-0341

Email: ajsanyal@hsc.vcu.edu