Review article on clinical significance and management of hyponatremia in liver cirrhosis
- B. Sri Vaishnavi Pharm D, V Year Ratnam Institute of Pharmacy, spsr Nellore, Andhra Pradesh.
- K.Akshya Kumari Pharm D, V Year Ratnam Institute of Pharmacy, spsr Nellore, Andhra Pradesh.
- G.Sathish Pharm D, V Year Ratnam Institute of Pharmacy, spsr Nellore, Andhra Pradesh.
-
P. Narayana Swamy
Associate professor, Department of Pharmacy Practice, Ratnam Institute of Pharmacy, spsr Nellore, Andhra Pradesh.
swamycool@gmail.com
- Y. Ramesh Professor and Head, Department of Pharmacy Practice, Ratnam Institute of Pharmacy, spsr Nellore, Andhra Pradesh.
- Y. Prapurna Chandra Principal of Ratnam Institute of Pharmacy, spsr Nellore, Andhra Pradesh.
Abstract
Hyponatremia is commonly observed in Liver cirrhosis patients, particularly in advanced stages with various complications and high mortality. The prevalence of hyponatremia in cirrhotic patients is approximately 50%., More frequently observed hyponatremia is hypervolemic hyponatremia, which occurs due to the overactivation of sodium and water retention mechanisms in response to effective arterial hypovolemia.Whereas hypovolemic hyponatremia typically results from excessive fluid loss, often due to diuretic therapy or diarrhea.In this review, we can figure out the relation between hyponatremia with clinical outcomes and management. Hyponatremia is a significant predictor of mortality and is associated with an increased risk of hepatorenal syndrome, altered mental status, infections, and poor post-transplantation outcomes. In treating hyponatremia, distinguishing between hypovolemic and hypervolemic types is essential.In hypervolemic hyponatremia,the management should be initiated only in the symptomatic patients. Prevents further declines in sodium levels by discontinuing diuretics and implementing fluid restriction. Currently, only albumin infusions can be routinely recommended, while other treatments such as vaptans, splanchnic vasoconstrictors, niravoline, or osmotic diuretics are reserved for specific scenarios, such as impending liver transplantation, or require careful indication.
Keywords:
Hyponatremia, liver cirrhosis, mortality, fluid restriction, vaptanes, liver transplantation
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References
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1999–2003.
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473.
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28) European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J. Hepatol. 2010, 53, 397–417.
29) Bichet, D.G.; Groves, B.M.; Schrier, R.W. Mechanisms of improvement of water and sodium excretion by immersion in decompensated cirrhotic patients. Kidney Int. 1983, 24, 788–794.
30) 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(S1):S95.
31) Cardenas A, Gines P, Marotta P, et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J Hepatol 2012;56:571- 578.
32) Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012;367:2407-2418.
33) Dahl E, Gluud LL, Kimer N, et al. Meta-analysis: The safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatremia. Aliment Pharmacol Ther 2012; 36:619-626.
34) Chishina H, Hagiwara S, Nishida N, et al. Clinical factors predicting the effect of Tolvaptan for refractory ascites in patients with decompensated liver cirrhosis. Dig Dis 2016;34:659-664.
35) Atsukawa M, Tsubota A, Kato K, et al. Analysis of factors predicting the response totolvaptan in patients with liver cirrhosis and hepatic. J Gastroenterol Hepatol 2018;33:1256-1263.
2) 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.
3) Angeli, P.; Wong, F.; Watson, H.; Gines, P. Hyponatremia in cirrhosis: Results of a patient population survey. Hepatology 2006, 44, 1535–1542.
4) IwakiriY. The molecules: Mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hyper tension. J Clin Gastroenterol 2007;41(Suppl. 3):S288-S294.
5) Gines P, Cardenas A. The management of ascites and hyponatremia in cirrhosis. Semin Liver Dis 2008;28:43-58.
6) Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mor tality among patients on the liver-transplant waiting list. N Engl J Med 2008;359:1018-1026.
7) Sterns RH. Disorders of plasma sodium—causes, consequences, and correction. N Engl J Med 2015;372:55-65.
8) Jimenez JV, Carrillo-Perez DL, Rosado-Canto R, et al. Electrolyte and acid-base disturbances in end-stage liver disease: A physiological approach. Dig Dis Sci 2017;628:1855-1871.
9) HaussingerD. Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 2006; 43:1187-1190.
10) Heins J, Zwingmann C. Organic osmolytes in hyponatremia and ammonia toxicity. Metab Brain Dis 2010;25:81-89.
11) Costa, D.; Simbrunner, B.; Jachs, M.; Hartl, L.; Bauer, D.; Paternostro, R.; Schwabl, P.; Scheiner, B.; Stattermayer, A.F.; Pinter, M.; et al. Systemic Inflammation Increases across Distinct Stages of Advanced Chronic Liver Disease and Correlates with Decompensation and Mortality. J. Hepatol. 2021, 74, 819–828.
12) Wang,Y.W.; Huo, T.I.; Yang, Y.Y.; Hou, M.C.; Lee, P.C.;
Lin, H.C.; Lee, F.Y.; Chi, C.W.; Lee, S.D. Correlation and comparison of the model for end-stage liver disease, portal pressure, and serum sodium for outcome prediction in patients with liver cirrhosis. J. Clin. Gastroenterol. 2007, 41, 706–712.
13) Narasimha GL, Dornadula GR. A Case Report on Pleural Effusion Induced by Pulmonary Tuberculosis Reactivation. International Journal of Science and Research (IJSR) ISSN: 2319-7064, Volume 8 Issue 8, August 2019.
14) Mathur, S.; Gane, E.J.; McCall, J.L.; Plank, L.D. Serum sodium and hydration status predict transplant-free survival independent of MELDscore in patients with cirrhosis. J. Gastroenterol. Hepatol. 2008, 23, 239–
243.
15) Sharawey, M.A.; Shawky, E.M.; Ali, L.H.; Mohammed, A.A.; Hassan, H.A.; Fouad, Y.M. Cystatin C: A predictor of hepatorenal syndrome in patients with liver cirrhosis. Hepatol. Int. 2011, 5, 927–933.
16) Tyagi, P.; Sharma, P.; Sharma, B.C.; Puri, A.S.; Kumar, A.; Sarin, S.K. Prevention of hepatorenal syndrome in patients with cirrhosis and ascites: A pilot randomized control trial between pentoxifylline and placebo. Eur. J. Gastroenterol. Hepatol. 2011, 23, 210–217.
17) Guevara, M.; Baccaro, M.E.; Torre, A.; Gomez-Anson, B.; Rios, J.; Torres, F.; Rami, L.; Monte-Rubio, G.C.; Martin-Llahi, M.; Arroyo, V.; et al. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: A prospective study with time- dependent analysis. Am. J. Gastroenterol. 2009, 104, 1382–1389.
18) Janicko, M.; Veseliny, E.; Abraldes, J.G.; Jarcuska, P. Serum sodium identifies patients with cirrhosis at high risk of hepatorenal syndrome. Z. Fur Gastroenterol. 2013, 51, 628–634.
19) Wunsch,E.; Naprawa, G.; Koziarska, D.; Milkiewicz, M.; Nowacki, P.; Milkiewicz, P. Serum natremia affects health-related quality of life in patients with liver cirrhosis: A prospective, single centre study. Ann. Hepatol. 2013, 12, 448–455.
20) Bossen, L.; Gines, P.; Vilstrup, H.; Watson, H.; Jepsen,
P. Serum sodium as a risk factor for hepatic encephalopathy in patients with cirrhosis and ascites. J. Gastroenterol. Hepatol. 2019, 34, 914–920.
21) Kim,J.H.; Lee, J.S.; Lee, S.H.; Bae, W.K.; Kim, N.H.; Kim,
K.A.; Moon, Y.S. The association between the serum sodium level and the severity of complications in liver cirrhosis. Korean J. Intern. Med. 2009, 24, 106–
112.
22) Watson, H.; Guevara, M.; Vilstrup, H.; Gines, P. Improvement of hyponatremia in cirrhosis is associated with improved complex information processing. J. Gastroenterol. Hepatol. 2019, 34,
1999–2003.
23) Ahluwalia, V.; Wade, J.B.; Thacker, L.; Kraft, K.A.; Sterling, R.K.; Stravitz, R.T.; Fuchs, M.; Bouneva, I.; Puri, P.; Luketic, V.; et al. Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis. J. Hepatol. 2013, 59, 467–
473.
24) Gunturu LN, Pamayyagari K, Dornadula GR. A Case Report on Herpes Zoster Eruption Associated with Chronic Obstructive Pulmonary Disease. International Journal of Therapeutic Applications, Volume 37, 2020.
25) Gines P, Berl T, Bernardi M, et al. Hyponatremia in cirrhosis: From pathogenesis to treatment. Hepatology 1998;28:851-864.
26) Gines P, Guevara M. Hyponatremia in cirrhosis: Pathogenesis, clinical significance, and management. Hepatology 2008;48:1002-1010.
27) Biggins, S.W.; Angeli, P.; Garcia-Tsao, G.; Ginès, P.; Ling, S.C.; Nadim, M.K.; Wong, F.; Kim, W.R. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021, 74, 1014–1048.
28) European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J. Hepatol. 2010, 53, 397–417.
29) Bichet, D.G.; Groves, B.M.; Schrier, R.W. Mechanisms of improvement of water and sodium excretion by immersion in decompensated cirrhotic patients. Kidney Int. 1983, 24, 788–794.
30) 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(S1):S95.
31) Cardenas A, Gines P, Marotta P, et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J Hepatol 2012;56:571- 578.
32) Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012;367:2407-2418.
33) Dahl E, Gluud LL, Kimer N, et al. Meta-analysis: The safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatremia. Aliment Pharmacol Ther 2012; 36:619-626.
34) Chishina H, Hagiwara S, Nishida N, et al. Clinical factors predicting the effect of Tolvaptan for refractory ascites in patients with decompensated liver cirrhosis. Dig Dis 2016;34:659-664.
35) Atsukawa M, Tsubota A, Kato K, et al. Analysis of factors predicting the response totolvaptan in patients with liver cirrhosis and hepatic. J Gastroenterol Hepatol 2018;33:1256-1263.
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B, S. V., K, A. K., G, S., P, N. S., Y, R., & Y, P. C. (2025). Review article on clinical significance and management of hyponatremia in liver cirrhosis. Asian Journal of Hospital Pharmacy, 5(1), 12-16. Retrieved from https://ajhponline.com/index.php/journal/article/view/96
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