Medical treatment of ascites in cirrhosis

Abstract

Medical treatment of cirrhotic ascites is essentially supportive, dictated by the patient's discomfort, impaired cardiovascular or respiratory function and potential for infection. Treatment of'simple' ascites (moderate fluid accumulation, serum albumin > 3.5 g/dl, serum creatinine < 1.5 mg/di, no electrolyte disturbance) is implemented sequentially. Only 10% of patients respond to dietary sodium restriction and bed rest; most require pharmacotherapy consisting of spironolactone, which increases the proportion of responding patients to 65% and loop diuretics, which may produce clinical improvement in an additional 20% (85% in all); in the remaining 15% of refractory patients, use of novel adjunctive therapies may be attempted. Patients with tense ascites, impaired renal function and electrolyte disturbances merit special consideration before diuretics are introduced. Spironolactone has long been a standard for the treatment of cirrhotic ascites because it directly antagonizes aldosterone. The loop diuretic most frequently added to spironolactone has been furosemide. However, there is preliminary evidence that torasemide may be more effective in some patients. Other investigational agents that may play a role in treatment of patients resistant to conventional drugs include ornipressin (a vasopressin analogue) and atrial natriuretic factor.Key words: Ascites; Atrial natriuretic peptide; Cirrhosis; Diuretics; Liver disease; Ornipressin; Spironolactone; Torasemide A brief overview of the pathophysiology of ascites formation in hepatic cirrhosis (1) can facilitate understanding both of the available therapeutic options and of the rationale for development of new therapeutic approaches. Traditionally, the initiating event of renal sodium and water retention in cirrhosis was considered to be ascites formation (underfilling hypothesis) or primary renal dysfunction due to a hepatorenal reflex (overflow hypothesis) (2). The alterations of systemic, splanchnic and renal haemodynamics, as well as increases in circulating levels of substances that cause sodium retention (3-6), are compatible with a decrease in effective blood volume as suggested by the underfilling hypothesis. These alterations, however, precede ascites formation. The recently introduced vasodilation hypothesis (7) reconciles many aspects of the underfilling theory and the overflow theory; it proposes that peripheral arterial vasodilation is the initiating event leading to decreased effective blood volume and renal sodium retention ( Table 1) and suggests that haemodynamic, hormonal and renal changes are augmented as liver disease becomes more severe. Peripheral arterial vasodilation leads to a decrease in effective arterial blood volume and, in compensation, increases in circulating levels of renin, aldosterone, noradrenaline and vasopressin, which result in renal vasoconstriction with sodium and water retention. With increasing severity of cirrhosis, the activation of these stimulants of sodium retention cannot restore effective blood volume. This, togethe...

Guidelines on the management of ascites in cirrhosis

“…54 Sodium restriction has been associated with lower diuretic requirement, faster resolution of ascites, and shorter hospitalisation. 55 56 In the past, dietary salt was often restricted to 22 or 50 mmol/day.…”

Evaluation of serum cystatin C concentration as a marker of renal function in patients with cirrhosis of the liver

“…1 3 Typically, these impairments in renal function in cirrhosis are of a functional nature which means that they are not accompanied by morphological changes and in the early stages can be reversed by medical intervention. [4][5][6] The extreme stage of this renal failure however, the hepatorenal syndrome, is rarely reversible, and liver transplantation is the only established therapy.…”

How impaired efficacy happened between Gancao and Yuanhua: Compounds, targets and pathways

“…These diuretics target on urine ion reabsorption and may cause electrolyte disturbances such as K + loss or hyperkalemia. Since these diseases are usually complicated with electrolyte disturbances, diuretics like furosemide may further worsen the electrolyte disturbances and have big limitations 35 . Recently, tolvaptan, a novel diuretic targeting AQP 2, has shown superior efficacy in treating ascites.…”