Ascites is a pathologic accumulation of fluid in the peritoneal cavity, most commonly due to portal hypertension caused by cirrhosis.

• Diuretic-resistant ascites: Ascites that cannot be mobilized or the early occurrence of ascites that cannot be prevented because of a lack of response to dietary sodium restriction and intensive diuretic treatment
• Diuretic-intractable ascites: Ascites that cannot be mobilized or the early recurrence of ascites that cannot be prevented because of the development of diuretic-induced complications that preclude the use of effective doses of diuretics
• Ascites may be graded according to the amount of fluid in the peritoneal cavity^1,2:
  1. Grade 1 (mild ascites): Ascites only detectable by ultrasound
  2. Grade 2 (moderate ascites): Ascites with moderate symmetric abdominal distention
  3. Grade 3 (large ascites): Ascites with marked abdominal distention

Peritoneal cavity fluid

Hydroperitoneum

Hydroperitonia

Hydrops abdominis

Ascites is the most common decompensation-defining complication of cirrhosis and is associated with worse prognosis. Ascites occurs at a rate of 7% to 10% annually in cirrhotic patients and occurs in ∼60% of individuals with cirrhosis within 10 yr of diagnosis.³ Cirrhosis is the cause of more than 80% of cases of ascites.⁴

• Important information to elicit within history:
  1. History of viral hepatitis
  2. Ongoing or previous heavy alcohol use
  3. Current or previous intravenous drug use and/or intranasal cocaine use
  4. Sexual history (e.g., unprotected sex with multiple partners, men who have sex with men)
  5. History of transfusions, tattoos, piercings, or incarceration
  6. Travel history and time spent in endemic regions for hepatitis
  7. Symptoms suggestive of peritoneal malignancy (e.g., weight loss, pain, palpable masses, rectal/vaginal bleeding)
  8. Other liver disease symptoms (e.g., increasing abdominal girth, jaundice, pruritus, confusion, pedal edema)
  9. Cardiac symptoms (e.g., pedal edema, shortness of breath, orthopnea, chest pain)
  10. Hypothyroid disease (fatigue, weight gain, constipation)
  11. History of ascites, prior treatment, large volume paracentesis (LVP) requirements and frequency
• Important physical exam findings:
  1. Protuberant abdomen (Fig. E1)
  2. Bulging flanks (can be present in obesity)
  3. Flank dullness to percussion (requires ∼1500 mL of fluid)
  4. Fluid wave on abdominal exam
  5. Lower extremity edema
  6. Shifting dullness on abdominal exam
  7. Physical signs associated with liver cirrhosis: Spider angiomas, jaundice, loss of body hair, skeletal muscle wasting (sarcopenia), Dupuytren contracture, bruising, palmar erythema, gynecomastia, testicular atrophy, rectal varices, and caput medusa

Pathophysiology of ascites (Fig. E2): Increased hepatic resistance to portal flow leads to portal hypertension. A portal pressure >12 mm Hg appears to be required for fluid retention.⁵ The splanchnic vessels respond by increased secretion of nitric oxide, causing splanchnic artery vasodilation. Vasodilation appears also to be mediated by the translocation of enteric bacteria and bacterial products. Early in the disease, increased plasma volume and increased cardiac output compensate for this vasodilation. However, as the disease progresses, the effective arterial blood volume decreases, causing sodium and fluid retention through activation of the renin-angiotensin system. Over time, activation of the sympathetic system causes renal vascular perfusion to decrease and may lead to hepatorenal syndrome. The change in capillary pressure causes increased permeability and retention of fluid in the abdomen.⁵ Principal causes of ascites formation categorized by underlying pathophysiology are summarized in Box E1.

• Chronic parenchymal liver disease, leading to portal hypertension
• Acute liver failure
• Noncirrhotic portal hypertension (e.g., portal vein clot)
• Peritoneal carcinomatosis
• Cardiac disease (e.g., heart failure, constrictive pericarditis)
• Hepatic venous outflow obstruction (e.g., Budd-Chiari syndrome, IVC webs)
• Protein losing enteropathy
• Peritoneal tuberculosis
• Nephrotic syndrome
• Pancreatitis

• Initial evaluation should always include:
  1. Diagnostic paracentesis. Initial laboratory tests on ascitic fluid should include a cell count and differential, albumin, total protein, culture, and Gram stain. A serum-ascites albumin gradient (SAAG) should be calculated in all patients. The SAAG is measured by subtracting the level of albumin in the ascitic fluid from a concurrent serum albumin measurement: SAAG = serum albumin-ascites albumin.
     1. If the SAAG is greater than 1.1 g/dL, the cause of ascites can be attributed to portal hypertension (e.g., cirrhosis, or post-sinusoidal elevated pressures as in Budd-Chiari syndrome or heart failure). A total ascitic protein level >2.5 g/dL may be indicative of cardiac ascites.⁴
     2. If SAAG is less than 1.1 g/dL, the cause of ascites is not portal hypertension (e.g., peritoneal carcinomatosis, tuberculous ascites, nephrotic syndrome). Optional tests on ascitis fluid that may aid in diagnosis include amylase, lactic dehydrogenase, acid-fast bacilli, and glucose levels.
     3. Cell count and differential: Ascitic fluid with greater than 250 neutrophils per cubic mm is diagnostic of spontaneous bacterial peritonitis (SBP).⁴
     4. Total ascitic fluid protein: Patients with protein concentration <1.5 g/dL have an increased risk of SBP.¹
     5. Cytology: Obtain in patients with a high index of suspicion for associated malignancy.²
  2. Aspartate aminotransferase, alanine transaminase, total and direct bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transpeptidase.
  3. CBC, coagulation studies (prothrombin time/INR).
  4. Electrolytes, blood urea nitrogen (BUN), creatinine.
• Causes of ascites in the normal or diseased peritoneum by SAAG are summarized in Table 1.
• Fig. 3 illustrates an algorithm for the approach to the differential diagnosis of ascites.

Figure 3 Algorithm for the approach to the differential diagnosis of ascites.

LDH, Lactic dehydrogenase; PMN, polymorphonuclear neutrophil; RBC, red blood cell; TB, tuberculosis; TG, triglyceride; TP, total protein; U/L, upper and lower; US, ultrasound.

From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.

• Abdominal ultrasound (Fig. E4) is the most sensitive measure for detecting ascitic fluid; a computed tomography or MRI scan is a viable alternative. Doppler studies of portal and hepatic veins should be added to rule out vascular etiology of ascites.
• Endoscopy of the upper GI tract to evaluate for esophageal and gastric varices if ascites is secondary to portal hypertension.

• Sodium-restricted diet (88 mmol/day or <2 g/day) is recommended for all patients with grade 2 ascites.
• Fluid restriction is only indicated in patients with hyponatremia (Na ≤125 mmol/L).
• All patients should be counseled on avoiding NSAIDs, ACE inhibitors, ARBs, alpha-adrenergic antagonists, and aminoglycoside antibiotics.

Patients with moderate-volume ascites causing only moderate discomfort may be treated on an outpatient basis with the following diuretic regimen:

1. Spironolactone: Start at 50 to 100 mg/day and titrate up every 3 to 4 days to a maximum dose of 400 mg/day (monotherapy or combination therapy with furosemide).²
2. Furosemide: Start at 40 mg/day and titrate up to 160 mg/day maximum (no role for monotherapy). A ratio of 40 mg/day of furosemide to 100 mg/day of spironolactone is an effective strategy in most patients but can modified based on kidney function and electrolytes.²
3. Monitor renal function and sodium levels carefully for signs of prerenal azotemia (in patients without edema, goal weight loss is 300 to 500 g/day; in patients with edema, goal weight loss is 800 to 1000 g/day). Furosemide alone is not recommended.²
4. Measurement of the urinary sodium level can be helpful to identify noncompliance with dietary sodium restriction and diuretic therapy. Patients excreting more than 78 mmol of sodium/day (24-h urine) and not losing weight likely have nonadherence with low Na diet. Patients with low Na excretion, less than 78 mmol daily, require up titration of diuretics and evaluation of compliance.

Patients with large-volume ascites causing marked discomfort or impairment in activities of daily living may be treated in the outpatient setting with diuretic therapy alone or in combination with large-volume paracentesis.

1. Large-volume paracentesis: Defined as >5L removed during a single paracentesis.
2. Diuretic therapy until loss of fluid is noted (maximum spironolactone 400 mg daily and furosemide 160 mg daily).
   1. No difference in long-term mortality rate was found; however, paracentesis is faster, more effective, and associated with fewer adverse effects.³
   2. Patients receiving large-volume paracentesis (>5L) should receive albumin replacement therapy at the dose of 6 to 8 g/L of ascites removed to prevent post-paracentesis circulatory dysfunction (PPCD).^2,6 Patients with renal dysfunction or hyponatremia should receive albumin for lower volumes as well.

Table 2 summarizes primary medical therapy and adjunctive medications used to increase the efficacy of primary therapy in the treatment of ascites.

• 5% to 10% of patients with large-volume ascites will be refractory to high-dose diuretic treatment.¹ Treatment strategies include repeated large-volume paracentesis with infusion of albumin every 2 to 4 wk or placement of a transjugular intrahepatic portosystemic shunt (TIPS).³ TIPS evaluation should include echocardiogram, assessment for hepatic encephalopathy (HE), and characterization of liver impairment.
• Long-term albumin administration (40 g weekly) may improve mortality, reduce episodes of HE, and delay accumulation of ascites compared to standard medical therapy.⁷ However, more research is needed before recommending the long-term use of albumin in routine management.²
• There are limited data on use of nonselective betablockers (NSBBs) in patients with diuretic-resistant ascites. Changes in mean arterial pressure (MAP) should be carefully monitored in patients on NSBBs, and these should be dose-reduced or stopped if substantial decrease in MAP is observed or systolic blood pressure is less than 90 mm Hg.⁴
• Patients known to have ascites should receive a diagnostic paracentesis if they develop any signs of SBP or upon any admission to the hospital even in the absence of these signs.
• Primary prophylaxis for SBP is recommended in patients with ascitic fluid protein <1.5 g/dL along with impaired renal function (creatinine ≥1.2 mg/dL or 106 micromol/L), BUN ≥25 mg/dL or 8.9 mmol/L or Na ≤130 mmol/L, or liver failure (Child-Pugh score ≥9 and bilirubin ≥3 mg/dL or 51 micromol/L).²
• Secondary prophylaxis for SBP should be instituted in all patients who were diagnosed with SBP in the form of a daily fluoroquinolone such as ciprofloxacin or norfloxacin, or double-strength trimethoprim-sulfamethoxazole.²
• Patients with known ascites who develop gastrointestinal bleeding should receive intravenous ceftriaxone for 7 days to prevent bacterial infections.
• Clinical use of vaptan agents is not currently recommended in cirrhotic patients.
• Oral midodrine 7.5 mg three times daily has been shown to increase urine volume, urine sodium, mean arterial pressure, and survival.³
• Peritoneovenous shunts or surgical portosystemic shunts have poor evidence and are not recommended.
• The Automated Low-Flow Ascites pump (not approved in North America) works by transporting small amounts of fluid from the peritoneal cavity to the bladder. Studies have shown improved symptoms and reduced LVP requirements.^3,8
• Liver transplantation remains definitive management for cirrhosis with refractory ascites.⁸ Referral to a transplant-capable center should be discussed.
• Table 3 summarizes the management of refractory ascites.
• A treatment approach to patients with malignant ascites is described in Fig. E5.

Figure E5 Malignant ascites, treatment approach.

From Abeloff MD: Clinical oncology, ed 3, Philadelphia, 2004, Churchill Livingstone.

• Development of ascites signals a shift to decompensated cirrhosis and close follow-up is required. 2-yr mortality reaches 75% in refractory ascites cases.³
• Monitor closely for worsening liver function and development of SBP.

Referral to hepatology at a transplant-capable center.

• Prevalence of SBP in patients with ascites ranges between 10% and 30%.⁶
  1. Presence of at least 250 neutrophils per cubic millimeter of ascitic fluid is diagnostic; however, ascitic culture should be obtained for every diagnostic paracentesis where SBP is being considered.
  2. Gram-negative bacteria such as E. coli are the most common isolates.⁶
  3. Third-generation cephalosporins are the treatment of choice for most patients. There should be consideration of multi-drug resistant organisms (MDRO) in patients with nosocomial infection, critical illness, or recent hospitalization. MDRO treatment may be tailored to local antimicrobiograms.
  4. Albumin improves survival in patients with SBP. Antibiotics should be administered with 1.5 g/kg albumin on treatment day 1 and 1.0 g/kg albumin on day 3 to prevent hepatorenal syndrome.⁶
  5. For patients diagnosed with SBP, a repeat diagnostic paracentesis may be obtained at 48 h after initiation of antibiotics to assess for response. A decrease of total ascitic polymorphonuclear neutrophil (PMN) count by at least 25% from baseline PMN count is considered a response.⁶
  6. By 1 yr post-SBP, 70% of patients have recurrence of SBP and should therefore receive ciprofloxacin 750 mg PO once/wk indefinitely for prophylaxis.⁶

• Prevention of liver cirrhosis through avoidance of long-term use of alcohol, immunization against hepatitis A and B, and treatment of hepatitis C
• In cirrhotic patients, following a low-sodium diet (<2 g daily)

Ascites (Patient Information)

Cirrhosis (Related Key Topic)