What is the pathophysiology and management of ascites in patients with liver disease, such as cirrhosis?

From the Guidelines

Ascites in liver disease is primarily managed with sodium restriction and diuretic therapy, with the goal of improving morbidity, mortality, and quality of life. The pathophysiology of ascites involves portal hypertension, decreased albumin production, and sodium retention, leading to fluid accumulation in the abdominal cavity 1. Management begins with moderate sodium restriction (2 g or 90 mmol/day) and diuretics (spironolactone with or without furosemide) as the first-line treatment in patients with cirrhosis and grade 2 ascites 1. Key considerations in management include:

• Diuretic therapy, typically starting with spironolactone 100mg daily and furosemide 40mg daily, which can be titrated up to maximum doses of 400mg and 160mg respectively while monitoring for electrolyte abnormalities
• Fluid restriction is only necessary for hyponatremia (sodium <125 mEq/L)
• Large-volume paracentesis (LVP) is indicated for tense or refractory ascites, with albumin infusion (6-8g per liter removed) recommended when removing >5 liters to prevent circulatory dysfunction
• TIPS (transjugular intrahepatic portosystemic shunt) may be considered for refractory ascites not responding to medical therapy
• Patients should be monitored for spontaneous bacterial peritonitis through diagnostic paracentesis when ascites is first detected or if patients develop fever, abdominal pain, or encephalopathy
• Long-term management should address the underlying liver disease, with abstinence from alcohol for alcoholic cirrhosis and consideration for liver transplantation in appropriate candidates
• Regular weight monitoring helps assess fluid status and treatment response, with weight gain >2kg in 3 days suggesting fluid retention requiring diuretic adjustment 1. The most recent and highest quality study, published in 2021 by the American Association for the Study of Liver Diseases, provides guidance on the diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome 1. Overall, the management of ascites in liver disease requires a comprehensive approach that addresses the underlying pathophysiology and incorporates ongoing monitoring and adjustment of treatment to optimize patient outcomes.

From the FDA Drug Label

In patients with hepatic cirrhosis and ascites, spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function, worsening hepatic encephalopathy and coma. WARNINGS In patients with hepatic cirrhosis and ascites, Furosemide tablets therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis.

The pathophysiology of ascites in patients with liver disease, such as cirrhosis, involves the accumulation of fluid in the peritoneal cavity due to portal hypertension and sodium retention. The management of ascites includes the use of diuretics like spironolactone and furosemide to reduce fluid accumulation and prevent complications like hepatic encephalopathy and coma.

• Key considerations in the management of ascites include:
  • Initiating therapy in a hospital setting to monitor for potential complications
  • Starting with low doses and titrating slowly to minimize the risk of adverse reactions
  • Monitoring renal function and electrolyte balance closely
  • Avoiding sudden alterations in fluid and electrolyte balance to prevent hepatic coma 2 3

From the Research

Pathophysiology of Ascites

• Ascites formation in patients with cirrhosis, portal hypertension, or both usually results from hyperdynamic circulatory dysfunction, where the retention of sodium and water is associated with the activation of the sympathetic and renin-angiotensin-aldosterone systems 4.
• The main factor of ascites formation is renal sodium retention due to activation of the renin-angiotensin-aldosterone system and sympathetic nervous system by the reduced effective volume secondary to splanchnic arterial vasodilation 5.
• The development of ascites is driven by portal hypertension, systemic inflammation, and splanchnic arterial vasodilation 6.
• The renin-angiotensin-aldosterone system, the sympathetic nervous system, and arginine vasopressin are responsible for sodium and water retention in patients with cirrhosis 7.

Management of Ascites

• Sodium restriction, diuretics, and large volume paracentesis are the mainstay of treatment in grade 1 to 3 ascites 5.
• The aim of medical therapy is to achieve a negative sodium balance and, consequently, fluid loss 7.
• Large-volume paracentesis is safe and effective in the management of tense ascites, but use of diuretic agents should be continued to prevent reaccumulation of ascites 7.
• In selected patients, long-term albumin use, norfloxacin prophylaxis, and transjugular intrahepatic portosystemic shunt reduce the risk of further decompensation and improve survival 6.
• Repeated large volume paracentesis plus albumin is the first line treatment for refractory ascites, and liver transplantation is recommended in patients with refractory ascites 5.

Complications of Ascites

• Complications of ascites (ie, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent/refractory ascites, and hepatic hydrothorax) further worsen survival 6.
• The hepatorenal syndrome has an associated grave prognosis, especially in patients who are not candidates for liver transplantation 7.
• The presence of ascites indicates the development of liver decompensation, and complications seen in conjunction with ascites may result in increased morbidity and mortality 4.