The Korean Journal of Medicine

  • 제82권1호
  • /
  • Pages.22-31
  • /
  • 2012
  • /
  • 1738-9364(pISSN)
  • /
  • 2289-0769(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
권호 표지
DOI QR코드

DOI QR Code

간경변성 복수 환자에서 Vaptan계열 약제의 유용성

Efficacy of Vaptans for Management of Ascites in Patients with Liver Cirrhosis

  • 최원혁 (건국대학교 의학전문대학원, 소화기병센터) ;
  • 이준성 (인제대학교 의과대학 일산백병원 내과)
  • Choe, Won-Hyeok (Digestive Disease Center, Konkuk University School of Medicine) ;
  • Lee, June-Sung (Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine)
  • 발행 : 2012.01.01
⟨ 이전 논문 다음 논문 ⟩

초록

Ascites is the most common complication of liver cirrhosis, but its pharmacological management is unsatisfactory in some patients because of a lack of response to treatment with conventional diuretics. Patients with cirrhosis and ascites generally have increased non-osmotic secretion of vasopressin which participates in the pathogenesis of fluid retention. Vaptans are a new family of orally active drugs that increase urine volume by antagonizing specifically the vasopressin receptors in the principal cells of the collecting ducts that have been shown to correct dilutional hyponatremia effectively. They also seem to be promising in the management of ascites by reducing the increased extracellular fluid volume in conditions associated with water retention including liver cirrhosis. However, there is a paucity of information on whether vaptans might have beneficial effect in enhancing ascites reduction in patients with cirrhosis. This review addresses the pharmacological actions of vaptans, their clinical applications, and future potential roles in managing patients with liver cirrhosis and ascites.

키워드

참고문헌

  1. Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology 1987;7:122-128. https://doi.org/10.1002/hep.1840070124
  2. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 1988;8:1151-1157. https://doi.org/10.1002/hep.1840080532
  3. Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology 2006;43(2 Suppl 1):S121-S131. https://doi.org/10.1002/hep.20993
  4. Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. J Hepatol 2007;46:927-934. https://doi.org/10.1016/j.jhep.2007.02.006
  5. 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. https://doi.org/10.1053/jhep.2003.50447
  6. Ruiz-del-Arbol L, Monescillo A, Arocena C, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology 2005;42:439-447. https://doi.org/10.1002/hep.20766
  7. Lee SS, Liu H. Cardiovascular determinants of survival in cirrhosis. Gut 2007;56:746-748. https://doi.org/10.1136/gut.2006.112169
  8. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004;350:1646-1654. https://doi.org/10.1056/NEJMra035021
  9. Gines 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. https://doi.org/10.1016/0016-5085(87)91007-9
  10. 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. https://doi.org/10.1016/S0168-8278(87)80067-3
  11. Gines 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. https://doi.org/10.1016/0016-5085(88)90691-9
  12. Sola R, Vila MC, Andreu M, et al. Total paracentesis with dextran 40 vs diuretics in the treatment of ascites in cirrhosis: a randomized controlled study. J Hepatol 1994;20:282-288. https://doi.org/10.1016/S0168-8278(05)80070-4
  13. Salerno F, Camma C, Enea M, Rossle M, Wong F. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology 2007;133:825-834. https://doi.org/10.1053/j.gastro.2007.06.020
  14. Arroyo V, Gines P. TIPS and refractory ascites: lessons from the recent history of ascites therapy. J Hepatol 1996; 25:221-223. https://doi.org/10.1016/S0168-8278(96)80078-X
  15. Gines 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. https://doi.org/10.1053/gast.2002.37073
  16. Decaux G, Soupart A, Vassart G. Non-peptide argininevasopressin antagonists: the vaptans. Lancet 2008;371:1624-1632. https://doi.org/10.1016/S0140-6736(08)60695-9
  17. Thibonnier M, Coles P, Thibonnier A, Shoham M. The basic and clinical pharmacology of nonpeptide vasopressin receptor antagonists. Annu Rev Pharmacol Toxicol 2001;41:175-202. https://doi.org/10.1146/annurev.pharmtox.41.1.175
  18. Ghali JK, Koren MJ, Taylor JR, et al. Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab 2006;91:2145-2152. https://doi.org/10.1210/jc.2005-2287
  19. Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006;355:2099-2112. https://doi.org/10.1056/NEJMoa065181
  20. Bankir L. Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptormediated effects. Cardiovasc Res 2001;51:372-390. https://doi.org/10.1016/S0008-6363(01)00328-5
  21. Folny V, Raufaste D, Lukovic L, et al. Pancreatic vasopressin V1b receptors: characterization in In-R1-G9 cells and localization in human pancreas. Am J Physiol Endocrinol Metab 2003;285:E566-E576. https://doi.org/10.1152/ajpendo.00148.2003
  22. Kumar S, Berl T. Vasopressin antagonists in the treatment of water-retaining disorders. Semin Nephrol 2008;28:279-288. https://doi.org/10.1016/j.semnephrol.2008.03.008
  23. Gross P. Treatment of hyponatremia. Intern Med 2008;47:885-891. https://doi.org/10.2169/internalmedicine.47.0918
  24. Gines P, Guevara M. Hyponatremia in cirrhosis: pathogenesis, clinical significance, and management. Hepatology 2008;48:1002-1010. https://doi.org/10.1002/hep.22418
  25. Gines P, Wong F, Watson H, Milutinovic S, del Arbol LR, Olteanu D; HypoCAT Study Investigators. Effects of satavaptan, a selective vasopressin V(2) receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: a randomized trial. Hepatology 2008;48:204-213. https://doi.org/10.1002/hep.22293
  26. Ferguson-Myrthil N. Novel agents for the treatment of hyponatremia: a review of conivaptan and tolvaptan. Cardiol Rev 2010;18:313-321. https://doi.org/10.1097/CRD.0b013e3181f5b3b7
  27. Gassanov N, Semmo N, Semmo M, Nia AM, Fuhr U, Er F. Arginine vasopressin (AVP) and treatment with arginine vasopressin receptor antagonists (vaptans) in congestive heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Eur J Clin Pharmacol 2011;67:333-346. https://doi.org/10.1007/s00228-011-1006-7
  28. Boyer TD. Tolvaptan and hyponatremia in a patient with cirrhosis. Hepatology 2010;51:699-702. https://doi.org/10.1002/hep.23522
  29. Blumenfeld JD, Tepler J, Mauer A, Coller B, Bichet DG, Smith B. Tolvaptan inhibition of desmopressin effects on coagulation factors in a patient with decreased von Willebrand factor and polycystic kidney disease. Blood 2011;118:474-476. https://doi.org/10.1182/blood-2011-04-347328
  30. Yamaguchi K, Shijubo N, Kodama T, et al. Clinical implication of the antidiuretic hormone (ADH) receptor antagonist mozavaptan hydrochloride in patients with ectopic ADH syndrome. Jpn J Clin Oncol 2011;41:148-152. https://doi.org/10.1093/jjco/hyq170
  31. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N; Conivaptan Study Group. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 2007;27:447-457. https://doi.org/10.1159/000106456
  32. Annane D, Decaux G, Smith N; Conivaptan Study Group. Efficacy and safety of oral conivaptan, a vasopressinreceptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci 2009;337:28-36. https://doi.org/10.1097/MAJ.0b013e31817b8148
  33. Gheorghiade M, Konstam MA, Burnett JC Jr, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA 2007;297:1332-1343. https://doi.org/10.1001/jama.297.12.1332
  34. Konstam MA, Gheorghiade M, Burnett JC Jr, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 2007;297:1319-1331. https://doi.org/10.1001/jama.297.12.1319
  35. Cardenas A, Gines P, Marotta P, et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis . J Hepatol 2011 Oct 23 [Epub].
  36. Okita K, Sakaida I, Okada M, et al. A multicenter, open-label, dose-ranging study to exploratively evaluate the efficacy, safety, and dose-response of tolvaptan in patients with decompensated liver cirrhosis. J Gastroenterol 2010; 45:979-987. https://doi.org/10.1007/s00535-010-0240-6
  37. Gerbes AL, Gülberg V, Gines P, et al. Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial. Gastroenterology 2003;124:933-939. https://doi.org/10.1053/gast.2003.50143
  38. Wong F, Blei AT, Blendis LM, Thuluvath PJ. 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. https://doi.org/10.1053/jhep.2003.50021
  39. Abraham WT, Aranda JM, Boehmer JP, et al. Rationale and design of the treatment of hyponatremia based on lixivaptan in NYHA class III/IV cardiac patient evaluation (THE BALANCE) study. Clin Transl Sci 2010;3:249-253. https://doi.org/10.1111/j.1752-8062.2010.00217.x
  40. Gassanov N, Biesenbach E, Caglayan E, Nia A, Fuhr U, Er F. Natriuretic peptides in therapy for decompensated heart failure. Eur J Clin Pharmacol 2011 Sep 8 [Epub].
  41. Wong F, Watson H, Gerbes A, et al. Satavaptan for the management of ascites in cirrhosis: efficacy and safety across the spectrum of ascites severity. Gut 2011 Aug 11 [Epub].
  42. Wong F, Gines P, Watson H, et al. Effects of a selective vasopressin V2 receptor antagonist, satavaptan, on ascites recurrence after paracentesis in patients with cirrhosis. J Hepatol 2010;53:283-290. https://doi.org/10.1016/j.jhep.2010.02.036
  43. Gines P, Wong F, Watson H, et al. Clinical trial: short-term effects of combination of satavaptan, a selective vasopressin V2 receptor antagonist, and diuretics on ascites in patients with cirrhosis without hyponatraemia: a randomized, doubleblind, placebo-controlled study. Aliment Pharmacol Ther 2010;31:834-845.