A guide to diagnosing and managing ascites in cirrhosis

,; ,; ,; ,

doi:10.12788/jfp.0186

Applied Evidence

A guide to diagnosing and managing ascites in cirrhosis

J Fam Pract. 2021 May;70(4):174-181 | 10.12788/jfp.0186

PDF Download

References

1. Runyon BA, Montano AA, Akriviadis EA, et al. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med. 1992;117:215-220.

2. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217-231.

3. Gordon FD. Ascites. Clin Liver Dis. 2012;16:285-299.

4. Schrier RW, Arroyo V, Bernardi M, et al. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151-1157.

5. Arroyo V, Terra C, Gines P. Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome. J Hepatol. 2007;46:935-946.

6. Bernardi M, Moreau R, Angeli P, et al. Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015;63:1272-1284.

7. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60:1310-1324.

8. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61:1385-1396.

9. Oey RC, van Buuren HR, de Man RA. The diagnostic work-up in patients with ascites: current guidelines and future prospects. Neth J Med. 2016;74:330-335.

10. de Kerguenec C, Hillaire S, Molinié V, et al. Hepatic manifestations of hemophagocytic syndrome: a study of 30 cases. Am J Gastroenterol. 2001;96:852-857.

11. Milić S, Lulić D, Štimac D. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World J Gastroenterol. 2014;20:9330-9337.

12. Aron-Wisnewsky J, Clement K, Pépin J-L. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism. 2016;65:1124-1135.

13. Li CP, Lee FY, Hwang SJ, et al. Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Scand J Gastroenterol. 1999;34:520-523.

14. Cavanaugh J. Gynecomastia and cirrhosis of the liver. Arch Intern Med. 1990;150:563-565.

15. Karnath B. Stigmata of chronic liver disease. Hosp Phys. 2003;7:14-16,28.

16. Schipper HG, Godfried MH. [Physical diagnosis--ascites]. Ned Tijdschr Geneeskd. 2001;145:260-264.

17. Cattau EL, Jr., Benjamin SB, Knuff TE, et al. The accuracy of the physical examination in the diagnosis of suspected ascites. JAMA. 1982;247:1164-1166.

18. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406-460.

19. Runyon BA, AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology 2009;49:2087-2107.

20. EASL Clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182-236.

21. Runyon BA. Care of patients with ascites. New Engl J Med. 1994;330:337-342.

22. Sakai H, Sheer TA, Mendler MH, et al. Choosing the location for non-image guided abdominal paracentesis. Liver Int. 2005;25:984-986.

23. Mercaldi CJ, Lanes SF. Ultrasound guidance decreases complications and improves the cost of care among patients undergoing thoracentesis and paracentesis. Chest. 2013;143:532-538.

24. Ennis J, Schultz G, Perera P, et al. Ultrasound for detection of ascites and for guidance of the paracentesis procedure: technique and review of the literature. Int J Clin Med. 2014;5:1277-1293.

25. Runyon BA, Canawati HN, Akriviadis EA. Optimization of ascitic fluid culture technique. Gastroenterology. 1988;95:1351-1355.

26. Akriviadis EA, Runyon BA. Utility of an algorithm in differentiating spontaneous from secondary bacterial peritonitis. Gastroenterology 1990;98:127-133.

27. Hoefs JC. Serum protein concentration and portal pressure determine the ascitic fluid protein concentration in patients with chronic liver disease. J Lab Clin Med. 1983;102:260-273.

28. Farias AQ, Silvestre OM, Garcia-Tsao G, et al. Serum B-type natriuretic peptide in the initial workup of patients with new onset ascites: a diagnostic accuracy study. Hepatology. 2014;59:1043-1051.

29. Gupta R, Misra SP, Dwivedi M, et al. Diagnosing ascites: value of ascitic fluid total protein, albumin, cholesterol, their ratios, serum-ascites albumin and cholesterol gradient. J Gastroenterol Hepatol. 1995;10:295-299.

30. Runyon BA. Management of adult patients with ascites due to cirrhosis: update 2012. AASLD Practice Guideline. Accessed April 28, 2021. www.aasld.org/sites/default/files/2019-06/AASLDPracticeGuidelineAsciteDuetoCirrhosisUpdate2012Edition4_.pdf

31. Morando F, Rosi S, Gola E, et al. Adherence to a moderate sodium restriction diet in outpatients with cirrhosis and ascites: a real-life cross-sectional study. Liver Int. 2015;35:1508-1515.

32. Bernardi M, Laffi G, Salvagnini M, et al. Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content. Liver. 1993;13:156-162.

33. Angeli P, Fasolato S, Mazza E, et al. Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut. 2010;59:98-104.

34. 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.

35. Grattagliano I, Ubaldi E, Bonfrate L, et al. Management of liver cirrhosis between primary care and specialists. World J Gastroenterol. 2011;17:2273-2282.

36. Pockros PJ, Reynolds TB. Rapid diuresis in patients with ascites from chronic liver disease: the importance of peripheral edema. Gastroenterology. 1986;90:1827-1833.

37. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397-417.

38. 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.

39. 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.

40. 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.

41. Bernardi M, Caraceni P, Navickis RJ, et al. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012;55:1172-1181.

42. Bureau C, Thabut D, Oberti F, et al. Transjugular intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites. Gastroenterology. 2017;152:157-163.

43. Fagiuoli S, Bruno R, Debernardi Venon W, et al. Consensus conference on TIPS management: techniques, indications, contraindications. Dig Liver Dis. 2017;49:121-137.

44. Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716-721.

45. Salerno F, Guevara M, Bernardi M, et al. Refractory ascites: pathogenesis, definition and therapy of a severe complication in patients with cirrhosis. Liver Int. 2010;30:937-947.

46. Caraceni P, Riggio O, Angeli P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet. 2018;391:2417-2429.

47. Solà E, Solé C, Simón-Talero M, et al. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial. J Hepatol. 2018;69:1250-1259.

48. Fasolato S, Angeli P, Dallagnese L, et al. Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features. Hepatology. 2007;45:223-229.

49. Hoefs JC, Canawati HN, Sapico FL, et al. Spontaneous bacterial peritonitis. Hepatology. 2007;2:399-407.

50. 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.

51. Lenz K, Kapral C, Gegenhuber A, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2004;39:865-866.

52. Sigal SH, Stanca CM, Fernandez J, et al. Restricted use of albumin for spontaneous bacterial peritonitis. Gut. 2007;56:597-599.

53. Fernández J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133:818-824.

54. Boyer TD, Zia P, Reynolds TB. Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. Gastroenterology. 1979;77:215-222.

55. Grattagliano I, Ubaldi E, Portincasa P, et al. Liver disease: early signs you may be missing. J Fam Pract. 2009;58:514-521.

56. Bini EJ, Weinshel EH, Generoso R, et al. Impact of gastroenterology consultation on the outcomes of patients admitted to the hospital with decompensated cirrhosis. Hepatology. 2001;34:1089-1095.

57. Volk ML, Tocco RS, Bazick J, et al. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol. 2012;107:247-252.

58. Morando F, Maresio G, Piano S, et al. How to improve care in outpatients with cirrhosis and ascites: a new model of care coordination by consultant hepatologists. J Hepatol. 2013;59:257-264.

Calculating serum ascites albumin gradient (SAAG) is recommended as it has been shown to better characterize ascitic fluid than total protein-based tests.²⁷ SAAG is calculated by subtracting the level of ascitic fluid albumin from serum albumin level (SAAG = serum albumin – ascitic fluid albumin). A SAAG ≥ 1.1 g/dL is consistent with portal hypertension,²⁸ with approximately 97% accuracy.

After calculating SAAG, look at total protein levels in ascitic fluid. Total protein concentration ≥ 2.5 g/dL with SAAG ≥ 1.1 g/dL has a 78.3% diagnostic accuracy in determining heart failure as the cause of ascites, with a sensitivity of 53.3% and specificity of 86.7%.²⁸ On the other hand, a value of total protein < 2.5 g/dL indicates cirrhosis, liver failure, or acute hepatitis as the cause of fluid build-up.²⁹ Stepwise evaluation of SAAG and total protein and how they can point toward the most likely cause of ascites is presented in FIGURE 2.^27-29

Management

Noninvasive measures

Sodium restriction. The aim of treatment for uncomplicated clinically apparent ascites is sodium restriction and removal of fluid from the body. Dietary salt restriction is complicated, and care should be taken to properly educate patients. Salt restriction advised in the literature has shifted from a strict measure of < 2 g/d³⁰ to more moderate strategies (described below).¹⁸

The 2 main reasons for this easing of restriction are issues with patient compliance and concerns about adverse effects with aggressive salt-restricted diets. One study assessing patient compliance with a salt-restricted diet found that more than two-thirds of the patients were noncompliant,³¹ and 65% of the patients incorrectly assumed they were following the plan, which suggests poor dietary education.³¹ Of the group that was compliant, 20% actually decreased their caloric intake, which can be detrimental in liver disease.³¹ Concerns have been raised that aggressive salt restriction along with diuretic use can lead to diuretic-induced hyponatremia and renal failure.³² Current European Association for the Study of the Liver (EASL) guidelines recommend salt restriction to a more moderate degree (80-120 mmol/d of sodium). This is equivalent to 4.9-6.9 g of salt (1 tablespoon is roughly equivalent to 6 g or 104 mmol of sodium).¹⁸

Diuretics. Initiation and dosage of diuretic therapy is a matter of some controversy. Historically, simultaneous administration of a loop diuretic and mineralocorticoid receptor blocker were recommended: 40 mg furosemide and 100 mg spironolactone, keeping the ratio constant with any dosage increases. This was based on a randomized controlled trial (RCT) showing that the combined diuretic therapy effectively mobilized ascites in a shorter period of time and with less frequent adverse effects (eg, hyperkalemia) compared with initial monotherapy.³³

Continue to: On the other hand...