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Semin Liver Dis 2008; 28(1): 043-058
DOI: 10.1055/s-2008-1040320
© Thieme Medical Publishers

The Management of Ascites and Hyponatremia in Cirrhosis

Pere Ginès1 , Andrés Cárdenas2
  • 1Liver Unit, Hospital Clínic and University of Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Ciber de Enfermedades Hepaticas y Digestivas (CIBERHED), Barcelona, Spain
  • 2GI Unit, Hospital Clínic and University of Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Ciber de Enfermedades Hepaticas y Digestivas (CIBERHED), Barcelona, Spain
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Publication History

Publication Date:
22 February 2008 (online)

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ABSTRACT

Ascites is the most common complication of cirrhosis and is associated with an increased risk for the development of infections, dilutional hyponatremia, renal failure, and mortality. Cirrhotic patients who develop ascites and associated complications have a low probability of long-term survival without liver transplantation, and therefore should be referred for evaluation of liver transplantation. While the initial management of uncomplicated ascites with low-sodium diet and diuretic treatment is straightforward in the majority of patients, there is a group of patients who fail to respond to diuretics and develop refractory ascites. The development of specific associated complications such as dilutional hyponatremia may further challenge the management of patients with ascites. New pharmacological agents such as the V2 receptor antagonists, drugs that directly antagonize the effects of elevated plasma antidiuretic hormone levels, induce solute-free water diuresis and seem to be promising in the management of patients with cirrhosis, ascites, and dilutional hyponatremia. This article focuses on the pathophysiology, clinical consequences, current management, and new treatment modalities for ascites and dilutional hyponatremia in cirrhosis.

KEYWORDS

Ascites - hyponatremia - vaptans

REFERENCES

  • 1 Minino A M, Heron M P, Smith B L. Deaths: preliminary data for 2004.  Natl Vital Stat Rep. 2006;  54 1-49
    PubMedGoogle Scholar
  • 2 Ginès P, Quintero E, Arroyo V et al.. Compensated cirrhosis: natural history and prognostic factors.  Hepatology. 1987;  7 122-128
    CrossrefPubMedGoogle Scholar
  • 3 Planas R, Montoliu S, Ballesté B et al.. Natural history of patients hospitalized for management of cirrhotic ascites.  Clin Gastroenterol Hepatol. 2006;  4 1385-1394
    CrossrefPubMedGoogle Scholar
  • 4 Ginès A, Escorsell A, Ginès P et al.. Incidence, predictive factors, and prognosis of hepatorenal syndrome in cirrhosis.  Gastroenterology. 1993;  105 229-236
    CrossrefPubMedGoogle Scholar
  • 5 Angeli P, Wong F, Watson H, Ginès P. CAPPS Investigators . Hyponatremia in cirrhosis: results of a patient population survey.  Hepatology. 2006;  44 1535-1542
    CrossrefPubMedGoogle Scholar
  • 6 Ginès P. Vaptans: a promising therapy in the management of advanced cirrhosis.  J Hepatol. 2007;  46 1150-1152
    CrossrefPubMedGoogle Scholar
  • 7 Schrier R W, Arroyo V, Bernardi M, Epstein M, Henriksen J H, Rodés J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis.  Hepatology. 1988;  8 1151-1157
    CrossrefPubMedGoogle Scholar
  • 8 Iwakiri Y, Groszmann R. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule.  Hepatology. 2006;  43 S121-S131
    CrossrefPubMedGoogle Scholar
  • 9 Iwakiri Y, Groszmann R. Vascular endothelial dysfunction in cirrhosis.  J Hepatol. 2007;  46 927-934
    CrossrefPubMedGoogle Scholar
  • 10 Wiest R, Das S, Cadelina G et al.. Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility.  J Clin Invest. 1999;  104 1223-1233
    PubMedGoogle Scholar
  • 11 Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis.  Hepatology. 2005;  41 422-433
    CrossrefPubMedGoogle Scholar
  • 12 Riordan S M, Williams R. The intestinal flora and bacterial infection in cirrhosis.  J Hepatol. 2006;  45 744-757
    CrossrefPubMedGoogle Scholar
  • 13 Ruiz-del-Arbol L, Urman J, Fernández J et al.. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis.  Hepatology. 2003;  38 1210-1218
    CrossrefPubMedGoogle Scholar
  • 14 Ruiz-del-Arbol L, Monescillo A, Arocena C et al.. Circulatory function and hepatorenal syndrome in cirrhosis.  Hepatology. 2005;  42 439-447
    CrossrefPubMedGoogle Scholar
  • 15 Lee S S, Liu H. Cardiovascular determinants of survival in cirrhosis.  Gut. 2007;  56 746-748
    CrossrefPubMedGoogle Scholar
  • 16 Sherlock S, Dooley J. Ascites. In: Sherlock S, Dooley J Diseases of the Liver and Biliary System. 11th ed. Oxford, England; Blackwell Science 2002: 127-146
    Google Scholar
  • 17 Ginès P, Cárdenas A, Arroyo V, Rodés J. Management of cirrhosis and ascites.  N Engl J Med. 2004;  350 1646-1654
    CrossrefPubMedGoogle Scholar
  • 18 Cárdenas A, Arroyo V. Ascites. In: Al-Knawy B, Sniffman M, Wiesner R Hepatology: A Practical Approach. Philadelphia; Elsevier Science 2005: 347-360
    Google Scholar
  • 19 Moore K P, Wong F, Ginès P et al.. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club.  Hepatology. 2003;  38 258-266
    PubMedGoogle Scholar
  • 20 Runyon B A. Management of adult patients with ascites due to cirrhosis.  Hepatology. 2004;  39 841-856
    CrossrefPubMedGoogle Scholar
  • 21 Ghassemi S, Garcia-Tsao G. Prevention and treatment of infections in patients with cirrhosis.  Best Pract Res Clin Gastroenterol. 2007;  21 77-93
    CrossrefPubMedGoogle Scholar
  • 22 Runyon B A, Antillon M R, Akriviadis E A, McHutchison J G. Bedside inoculation of blood culture bottles is superior to delayed inoculation in the detection of spontaneous bacterial peritonitis.  J Clin Microbiol. 1990;  28 2811-2812
    PubMedGoogle Scholar
  • 23 Ginès P, Berl T, Bernardi M et al.. Hyponatremia in cirrhosis: from pathogenesis to treatment.  Hepatology. 1998;  28 851-864
    CrossrefPubMedGoogle Scholar
  • 24 Henkel A S, Buchman A L. Nutritional support in patients with chronic liver disease.  Nat Clin Pract Gastroenterol Hepatol.. 2006;  3 202-209
    CrossrefPubMedGoogle Scholar
  • 25 McCullough A J. Nutrition and malnutrition in liver disease. In: Wolfe MM, Davis GL, Farraye F, Giannella RA, Malagelada JR, Steer ML Therapy of Digestive Disorders. 2nd ed. Philadelphia; Saunders 2006: 67-83
    Google Scholar
  • 26 Kearns P J, Young H, Garcia G et al.. Accelerated improvement of alcoholic liver disease with enteral nutrition.  Gastroenterology. 1992;  102 200-205
    PubMedGoogle Scholar
  • 27 Cabrè E, Gonzalez-Hux F, Abad-Lacruz A et al.. Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics: a randomized controlled trial.  Gastroenterology. 1990;  98 715-720
    PubMedGoogle Scholar
  • 28 Perez-Ayuso R M, Arroyo V, Planas R et al.. Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites: relationship between the diuretic response and the activity of the renin-aldosterone system.  Gastroenterology. 1983;  84 961-968
    PubMedGoogle Scholar
  • 29 Santos J, Planas R, Pardo A et al.. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis: a randomized comparative study of efficacy and safety.  J Hepatol. 2003;  39 187-192
    CrossrefPubMedGoogle Scholar
  • 30 Li C P, Lee F Y, Hwang S J et al.. Treatment of mastalgia with tamoxifen in male patients with liver cirrhosis: a randomized crossover study.  Am J Gastroenterol. 2000;  95 1051-1055
    CrossrefPubMedGoogle Scholar
  • 31 Lee F Y, Lee S D, Tsai Y T et al.. A randomized controlled trial of quinidine in the treatment of cirrhotic patients with muscle cramps.  J Hepatol. 1991;  12 236-240
    CrossrefPubMedGoogle Scholar
  • 32 Angeli P, Albino G, Carraro P et al.. Cirrhosis and muscle cramps: evidence of a causal relationship.  Hepatology. 1996;  23 264-273
    CrossrefPubMedGoogle Scholar
  • 33 Ginès P, Arroyo V, Quintero E et al.. Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites: results of a randomized study.  Gastroenterology. 1987;  93 234-241
    PubMedGoogle Scholar
  • 34 Salerno F, Badalamenti S, Incerti P et al.. Repeated paracentesis and i.v. albumin infusion to treat “tense” ascites in cirrhotic patients. A safe alternative therapy.  J Hepatol. 1987;  5 102-108
    CrossrefPubMedGoogle Scholar
  • 35 Moore K P, Aithal G P. Guidelines on the management of ascites in cirrhosis.  Gut. 2006;  55(suppl 6) vi1-vi12
    CrossrefPubMedGoogle Scholar
  • 36 Ginès P, Tito L, Arroyo V et al.. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis.  Gastroenterology. 1988;  94 1493-1502
    PubMedGoogle Scholar
  • 37 Ruiz-del-Arbol L, Monescillo A, Jiménez W et al.. Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis.  Gastroenterology. 1997;  113 579-586
    CrossrefPubMedGoogle Scholar
  • 38 Ginès A, Fernández-Esparrach G, Monescillo A et al.. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis.  Gastroenterology. 1996;  111 1002-1010
    CrossrefPubMedGoogle Scholar
  • 39 Moreau R, Valla D C, 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 trial.  Liver Int. 2006;  26 46-54
    CrossrefPubMedGoogle Scholar
  • 40 Sola-Vera J, Minana 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 1147-1153
    CrossrefPubMedGoogle Scholar
  • 41 Fernández-Esparrach G, Guevara M, Sort P et al.. Diuretic requirements after therapeutic paracentesis in non-azotemic patients with cirrhosis: a randomized double-blind trial of spironolactone versus placebo.  J Hepatol. 1997;  26 614-620
    CrossrefPubMedGoogle Scholar
  • 42 Thomsen T W, Shaffer R W, White B, Setnik G S. Videos in clinical medicine: paracentesis.  N Engl J Med. 2006;  355 e21
    CrossrefPubMedGoogle Scholar
  • 43 Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease.  Aliment Pharmacol Ther. 2005;  21 525-529
    CrossrefPubMedGoogle Scholar
  • 44 Caldwell S H, Hoffman M, Lisman T et al.. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management.  Hepatology. 2006;  44 1039-1046
    CrossrefPubMedGoogle Scholar
  • 45 Cárdenas A, Guevara M, Ginès P. Paracentesis. In: Weinstein W, Hawkey CJ, Bosch J Clinical Gastroenterology and Hepatology. Philadelphia; Elsevier Science 2005: 1097-1100
    Google Scholar
  • 46 Sakai H, Sheer T A, Mendler M H, Runyon B A. Choosing the location for non-image guided abdominal paracentesis.  Liver Int. 2005;  25 984-986
    CrossrefPubMedGoogle Scholar
  • 47 Arroyo V, Ginès P, Gerbes A et al.. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis.  Hepatology. 1996;  23 164-176
    CrossrefPubMedGoogle Scholar
  • 48 Guardiola J, Baliellas C, Xiol X et al.. External validation of a prognostic model for predicting survival of cirrhotic patients with refractory ascites.  Am J Gastroenterol. 2002;  97 2374-2378
    PubMedGoogle Scholar
  • 49 Ginès P, Uriz J, Calahorra B et al.. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.  Gastroenterology. 2002;  123 1839-1847
    CrossrefPubMedGoogle Scholar
  • 50 Boyer T D, Haskal Z. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension.  Hepatology. 2005;  41 386-400
    CrossrefPubMedGoogle Scholar
  • 51 Bureau C, García-Pagan J C, Otal P et al.. Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study.  Gastroenterology. 2004;  126 469-475
    CrossrefPubMedGoogle Scholar
  • 52 Lebrec D, Giuily N, Hadengue A et al.. Transjugular intrahepatic portosystemic shunts-comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial.  J Hepatol. 1996;  25 135-144
    CrossrefPubMedGoogle Scholar
  • 53 Rossle M, Ochs A, Gulberg V et al.. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.  N Engl J Med. 2000;  342 1701-1707
    CrossrefPubMedGoogle Scholar
  • 54 Sanyal A J, Genning C, Reddy R K et al.. The North American Study for Treatment of Refractory Ascites.  Gastroenterology. 2003;  124 634-641
    CrossrefPubMedGoogle Scholar
  • 55 Salerno F, Merli M, Riggio O et al.. Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.  Hepatology. 2004;  40 629-635
    CrossrefPubMedGoogle Scholar
  • 56 Allard J P, Chau J, Sandokji K, Blendis L M, Wong F. Effects of ascites resolution after successful TIPS on nutrition in cirrhotic patients with refractory ascites.  Am J Gastroenterol. 2001;  96 2442-2447
    CrossrefPubMedGoogle Scholar
  • 57 Deltenre P, Mathurin P, Dharancy S et al.. Transjugular intrahepatic portosystemic shunt in refractory ascites: a meta-analysis.  Liver Int. 2005;  25 349-356
    CrossrefPubMedGoogle Scholar
  • 58 Albillos A, Banares R, Gonzales M et al.. A meta-analysis of transjugular intrahepatic portosystemic shunt versus paracentesis for refractory ascites.  J Hepatol. 2005;  43 990-996
    CrossrefPubMedGoogle Scholar
  • 59 D'Amico G, Luca A, Morabito A et al.. Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis.  Gastroenterology. 2005;  129 1282-1293
    CrossrefPubMedGoogle Scholar
  • 60 Salerno F, Camma C, Enea M et al.. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data.  Gastroenterology. 2007;  133 825-834
    CrossrefPubMedGoogle Scholar
  • 61 Cárdenas A, Ginès P. Management of refractory ascites.  Clin Gastroenterol Hepatol. 2005;  3 1187-1191
    CrossrefPubMedGoogle Scholar
  • 62 Llach J, Ginès P, Arroyo V et al.. Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites.  Gastroenterology. 1988;  94 482-487
    PubMedGoogle Scholar
  • 63 Guevara M, Cárdenas A, Uriz J, Ginès P. Prognosis of patients with ascites and cirrhosis. In: Ginès P, Arroyo V, Rodés J, Schrier R Ascites and Renal Dysfunction in Liver Disease. 2nd ed. Oxford; Blackwell Publishing 2005: 260-270
    Google Scholar
  • 64 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
    CrossrefPubMedGoogle Scholar
  • 65 Heuman D M, Abou-Assi S G, Habib A et al.. Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death.  Hepatology. 2004;  40 802-810
    CrossrefPubMedGoogle Scholar
  • 66 Biggins S W, Rodriguez H J, Bacchetti P, Bass N M, Robert J P, Terrault N A. Serum sodium predicts mortality in patients listed for liver transplantation.  Hepatology. 2005;  41 32-39
    CrossrefPubMedGoogle Scholar
  • 67 Ruf A E, Kremers W K, Chavez L L, Descalzi V I, Podesta L G, Villamil F G. Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone.  Liver Transpl. 2005;  11 336-343
    CrossrefPubMedGoogle Scholar
  • 68 Biggins S W, Kim W R, Terrault N A et al.. Evidence-based incorporation of serum sodium concentration into MELD.  Gastroenterology. 2006;  130 1652-1660
    CrossrefPubMedGoogle Scholar
  • 69 Luca A, Angermayr B, Bertolini G et al.. An integrated MELD model including serum sodium and age improves the prediction of early mortality in patients with cirrhosis.  Liver Transpl. 2007;  13 1174-1180
    CrossrefPubMedGoogle Scholar
  • 70 Mathur S, Gane E J, McCall J L, Plank L D. Serum sodium and hydration status predict transplant-free survival independent of MELD score in patients with cirrhosis.  J Gastroenterol Hepatol. 2007;  , April 19 (Epub ahead of print)
    PubMedGoogle Scholar
  • 71 Londoño M C, Cardenas A, Guevara M et al.. MELD score and serum sodium in the prediction of survival of patients with cirrhosis awaiting liver transplantation.  Gut. 2007;  56 1283-1290
    CrossrefPubMedGoogle Scholar
  • 72 Dawwas M F, Lewsey J D, Neuberger J M et al.. The impact of serum sodium concentration on mortality after liver transplantation: a cohort multicenter study.  Liver Transpl. 2007;  13 1115-1124
    CrossrefPubMedGoogle Scholar
  • 73 Londoño M C, Guevara M, Rimola A et al.. Hyponatremia impairs early posttransplantation outcome in patients with cirrhosis undergoing liver transplantation.  Gastroenterology. 2006;  130 1135-1143
    CrossrefPubMedGoogle Scholar
  • 74 Fernández-Varo G, Ros J, Cejudo-Martin P et al.. Effect of the V1a/V2-AVP receptor antagonist, conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites.  J Hepatol. 2003;  38 755-761
    CrossrefPubMedGoogle Scholar
  • 75 Decaux G. Difference in solute excretion during correction of hyponatremic patients with cirrhosis or syndrome of inappropriate secretion of antidiuretic hormone by oral vasopressin V2 receptor antagonist VPA-985.  J Lab Clin Med. 2001;  138 18-21
    CrossrefPubMedGoogle Scholar
  • 76 Ginès P, Wong F, Watson H R et al.. Effects of a selective vasopressin V2 receptor antagonist, satavaptan (SR121463B), in patients with cirrhosis and ascites without hyponatremia.  Hepatology. 2006;  44 691A
    PubMedGoogle Scholar
  • 77 Wong F, Ginès P, Watson H R et al.. Effects of a selective vasopressin V2 receptor antagonist, satavaptan (SR121463B), on recurrence of ascites after large volume paracentesis.  Hepatology. 2006;  44 180A
    PubMedGoogle Scholar
  • 78 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
    CrossrefPubMedGoogle Scholar
  • 79 Ortega R, Ginès P, Uriz J et al.. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, non-randomized study.  Hepatology. 2002;  36 941-948
    CrossrefPubMedGoogle Scholar
  • 80 Kalambokis G, Fotopoulos A, Economou M et al.. Effects of a 7-day treatment with midodrine in non-azotemic cirrhotic patients with and without ascites.  J Hepatol. 2007;  46 213-221
    CrossrefPubMedGoogle Scholar
  • 81 Lenaerts A, Codden T, Meunier J C et al.. Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system.  Hepatology. 2006;  44 844-849
    CrossrefPubMedGoogle Scholar
  • 82 Schrier R W. Water and sodium retention in edematous disorders: role of vasopressin and aldosterone.  Am J Med. 2006;  119(suppl 1) S47-S53
    CrossrefPubMedGoogle Scholar
  • 83 Ishikawa S E, Schrier R W. Pathogenesis of hyponatremia: the role of arginine vasopressin in cirrhosis. In: Ginès P, Arroyo V, Rodés J, Schrier RW Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis and Treatment. 2nd ed. Oxford; Blackwell Science 2005: 305-314
    Google Scholar
  • 84 Thibonnier M, Conarty D M, Preston J A, Wilkins P L, Berti-Mattera L N, Mattera R. Molecular pharmacology of human vasopressin receptors.  Adv Exp Med Biol. 1998;  449 251-276
    PubMedGoogle Scholar
  • 85 Kwon T H, Hager H, Nejsum L N, Andersen M L, Frokiaer J, Nielsen S. Physiology and pathophysiology of renal aquaporins.  Semin Nephrol. 2001;  21 231-238
    CrossrefPubMedGoogle Scholar
  • 86 Nielsen S, Frokiaer J, Marples D, Kwon T H, Agre P, Knepper M A. Aquaporins in the kidney: from molecules to medicine.  Physiol Rev. 2002;  82 205-244
    PubMedGoogle Scholar
  • 87 Esteva-Font C, Baccaro M E, Fernández-Llama P et al.. Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: relationship with ascites and hepatorenal syndrome.  Hepatology. 2006;  44 1555-1556
    CrossrefPubMedGoogle Scholar
  • 88 Wong F, Blei A T, Blendis L M, Thuluvath P J. A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: a multicenter, randomized, placebo-controlled trial.  Hepatology. 2003;  37 182-191
    CrossrefPubMedGoogle Scholar
  • 89 Gerbes A L, Gülberg V, Ginès P et al.. The VPA Study Group. Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial.  Gastroenterology. 2003;  124 933-939
    CrossrefPubMedGoogle Scholar
  • 90 Schrier R W, Gross P, Gheorghiade M et al.. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.  N Engl J Med. 2006;  355 2099-2112
    CrossrefPubMedGoogle Scholar
  • 91 Ginès P, Wong F, Milutinovic D et al.. Effects of satavaptan (SR121463B), a selective vasopressin V2 receptor antagonist on serum sodium concentration and ascites in patients with cirrhosis hyponatremia.  J Hepatol. 2006;  44 732A
    CrossrefPubMedGoogle Scholar
  • 92 Ginès P, Wong F, Watson H. Long-term improvement of serum sodium by the V2-receptor antagonist satavaptan in patients with cirrhosis and hyponatremia.  J Hepatol. 2007;  46 90A
    PubMedGoogle Scholar
  • 93 Fraser C L, Arieff A I. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy.  Am J Med. 1997;  102 67-77
    CrossrefPubMedGoogle Scholar
  • 94 Berl T, Verbalis J. Pathophysiology of water metabolism. In: Brenner & Rector's The Kidney. 7th ed. Philadelphia; Elsevier 2004: 857-920
    Google Scholar
  • 95 Verbalis J G, Gullans S R. Hyponatremia causes large sustained reductions in brain content of multiple organic osmolytes in rats.  Brain Res. 1991;  567 274-282
    CrossrefPubMedGoogle Scholar
  • 96 Verbalis J G. The syndrome of inappropriate secretion of antidiuretic hormone secretion and other hyposmolar disorders. In: Schrier R Diseases of the Kidney and Urinary Tract. 8th ed. Philadelphia, PA; Lippincott Williams & Wilkins 2007: 2214
    Google Scholar
  • 97 Halperin M L, Kamel K S. A new look at an old problem: therapy of chronic hyponatremia.  Nat Clin Pract Nephrol.. 2007;  3 2-3
    CrossrefPubMedGoogle Scholar
  • 98 Haussinger D, Laubenberger J, vom Dahl S et al.. Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy.  Gastroenterology. 1994;  107 1475-1480
    PubMedGoogle Scholar
  • 99 Häussinger D, Kircheis G, Fischer R, Schliess F, vom Dahl S. Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema.  J Hepatol. 2000;  32 1035-1038
    CrossrefPubMedGoogle Scholar
  • 100 Haussinger D. Low-grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis.  Hepatology. 2006;  43 1187-1190
    CrossrefPubMedGoogle Scholar
  • 101 Laubenberger J, Haussinger D, Bayer S et al.. Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis.  Gastroenterology. 1997;  112 1610-1616
    CrossrefPubMedGoogle Scholar
  • 102 Minguez B, Garcia-Pagan J C, Bosch J et al.. Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy.  Hepatology. 2006;  43 707-714
    CrossrefPubMedGoogle Scholar
  • 103 Seery J P, Taylor-Robinson S D. The application of magnetic resonance spectroscopy to the study of hepatic encephalopathy.  J Hepatol. 1996;  25 988-998
    CrossrefPubMedGoogle Scholar
  • 104 Butterworth R F. Pathophysiology of hepatic encephalopathy: a new look at ammonia.  Metab Brain Dis. 2002;  17 221-227
    CrossrefPubMedGoogle Scholar
  • 105 Butterworth R F. Pathogenesis of hepatic encephalopathy: new insights from neuroimaging and molecular studies.  J Hepatol. 2003;  39 278-285
    CrossrefPubMedGoogle Scholar
  • 106 Restuccia T, Gómez-Ansón B, Guevara M et al.. Effects of dilutional hyponatremia on brain organic osmolytes and water content in patients with cirrhosis.  Hepatology. 2004;  39 1613-1622
    CrossrefPubMedGoogle Scholar
  • 107 Córdoba J, Gottstein J, Blei A T. Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after porto-caval anastomosis.  J Hepatol. 1998;  29 589-594
    CrossrefPubMedGoogle Scholar
  • 108 Shawcross D L, Balata S, Olde Damink S W et al.. Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia.  Am J Physiol Gastrointest Liver Physiol. 2004;  287 G503-G509
    CrossrefPubMedGoogle Scholar
  • 109 Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride in intracranial pressure in patients with acute liver failure.  Hepatology. 2004;  39 464-470
    CrossrefPubMedGoogle Scholar
  • 110 Baccaro M E, Guevara M, Torre A et al.. Hyponatremia predisposes to hepatic encephalopathy in patients with cirrhosis: results of a prospective study with time-dependent analysis.  Hepatology. 2006;  44 118A
    PubMedGoogle Scholar
  • 111 Guevara M, Uriz J, Arcos E et al.. Hyponatremia is a risk factor of hepatic encephalopathy in cirrhosis: a post hoc time-dependent analysis of the international study group on refractory ascites trial.  Hepatology. 2006;  44 677A
    PubMedGoogle Scholar
  • 112 Ginès P, Smajda Lew E, Diamand F. Hyponatremia is a major determinant of impaired health-related quality of life in cirrhosis with ascites.  Hepatology. 2007;  46 744A
    PubMedGoogle Scholar
  • 113 Abbasoglu O, Goldstein R M, Vodapally M S et al.. Liver transplantation in hyponatremic patients with emphasis on central pontine myelinolysis.  Clin Transplant. 1998;  12 263-269
    PubMedGoogle Scholar
  • 114 Wszolek Z K, McComb R D, Pfeiffer R F et al.. Pontine and extrapontine myelinolysis following liver transplantation: relationship to serum sodium.  Transplantation. 1989;  48 1006-1012
    PubMedGoogle Scholar
  • 115 Jalan R, Mookerjee R, Cheshire L et al.. Albumin infusion for severe hyponatremia in patients with refractory ascites: a randomized clinical trial.  J Hepatol. 2007;  46 232A
    PubMedGoogle Scholar
  • 116 De Troyer A, Pilloy W, Broeckaert I, Demanet J C. Demeclocycline treatment of water retention in cirrhosis.  Ann Intern Med. 1976;  85 336-337
    PubMedGoogle Scholar
  • 117 Carrilho F, Bosch J, Arroyo V et al.. Renal failure associated with demeclocycline in cirrhosis.  Ann Intern Med. 1977;  87 195-197
    PubMedGoogle Scholar
  • 118 Decaux G, Mols P, Cauchie P et al.. Treatment of hyponatremic cirrhosis with ascites resistant to urea.  Nephron. 1986;  44 337-343
    PubMedGoogle Scholar
  • 119 Gadano A, Moreau R, Pessione F et al.. Aquaretic effects of niravoline, a kappa-opioid agonist, in patients with cirrhosis.  J Hepatol. 2000;  32 38-42
    PubMedGoogle Scholar
  • 120 Inoue T, Ohnishi A, Matsuo A et al.. Therapeutic and diagnostic potential of a vasopressin-2 antagonist for impaired water handling in cirrhosis.  Clin Pharmacol Ther. 1998;  63 561-570
    PubMedGoogle Scholar
  • 121 Thuluvath P J, Maheshwari A, Wong F et al.. Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites: a randomized, double-blind, placebo-controlled, single ascending dose study.  Aliment Pharmacol Ther. 2006;  24 973-982
    CrossrefPubMedGoogle Scholar
  • 122 Afdhal N, Cardenas A, Ginès P et al.. Randomized, placebo-controlled trial of tolvaptan, a novel V2-receptor antagonist, in hyponatremia: results of the SALT 2 trial with emphasis on efficacy and safety in cirrhosis.  Hepatology. 2005;  42 LB19A
    PubMedGoogle Scholar

Pere GinèsM.D. 

Liver Unit, Hospital Clínic, Villarroel 170

08036 Barcelona, Spain

Email: pgines@clinic.ub.es

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