What is the serum‑ascites albumin gradient (SAAG) and how is it interpreted in the evaluation of ascites?

Serum-Ascites Albumin Gradient (SAAG): Definition and Interpretation

The SAAG is calculated by subtracting the ascitic fluid albumin from the serum albumin (measured simultaneously), and a value ≥1.1 g/dL indicates portal hypertension with 97% accuracy, while <1.1 g/dL excludes portal hypertension and points to alternative causes such as peritoneal carcinomatosis or tuberculosis. 1, 2

How to Calculate SAAG

• Obtain serum and ascitic fluid samples on the same day 1
• Measure albumin concentration in both samples 1
• SAAG = Serum Albumin - Ascitic Fluid Albumin 1, 2

Interpretation of SAAG Values

High SAAG (≥1.1 g/dL): Portal Hypertension Present

• Indicates portal hypertension with approximately 97% diagnostic accuracy 1, 2, 3
• Common causes include:
  • Cirrhosis (most common in Western world) 1, 3
  • Cardiac ascites from right heart failure 1, 3
  • Massive liver metastases 1
  • Budd-Chiari syndrome (hepatic vein thrombosis) 2, 3
  • Sinusoidal obstruction syndrome 2, 3

Low SAAG (<1.1 g/dL): Portal Hypertension Absent

• Excludes portal hypertension with 97% accuracy 1, 3
• Common causes include:
  • Peritoneal carcinomatosis (most frequent malignant cause) 1, 3
  • Tuberculous peritonitis 1, 2, 3
  • Nephrotic syndrome 2, 3
  • Pancreatic ascites 3

Critical Distinction: Cardiac vs. Cirrhotic Ascites

When SAAG is ≥1.1 g/dL, measure ascitic fluid total protein to differentiate cardiac from cirrhotic causes: 3, 4

• High SAAG (≥1.1 g/dL) + High protein (>2.5 g/dL) = Cardiac ascites 1, 3, 4
• High SAAG (≥1.1 g/dL) + Low protein (<2.5 g/dL) = Cirrhotic ascites 3, 4

When to Order SAAG

According to the 2021 AASLD guidance: 1

• First episode of ascites: Order SAAG for all inpatients and outpatients 1
• Recurrent ascites: SAAG not routinely needed unless clinical picture changes 1

Treatment Implications Based on SAAG

High SAAG Ascites (≥1.1 g/dL)

• Patients typically respond to sodium restriction (2000 mg/day) and diuretics 2, 3, 4
• Initiate spironolactone 100 mg daily plus furosemide 40 mg daily 3, 4
• Treat underlying liver disease (e.g., alcohol cessation for alcoholic cirrhosis) 3

Low SAAG Ascites (<1.1 g/dL)

• Generally do NOT respond to sodium restriction and diuretics (except nephrotic syndrome) 2, 3
• Management must target the underlying disorder 3
• Avoid empiric diuretic therapy 3

Essential Pitfalls and Special Considerations

Mixed Ascites (Critical to Recognize)

• Approximately 5% of patients have two or more causes of ascites simultaneously 2, 3, 4
• Patients with portal hypertension PLUS a second cause still have SAAG ≥1.1 g/dL 2, 3, 4
• Example: Cirrhotic patient who develops peritoneal carcinomatosis will maintain high SAAG 3

Low SAAG in Cirrhotic Patients: A Diagnostic Challenge

• In patients with known cirrhosis, a low SAAG has low diagnostic yield (only 38% have identifiable cause) 5
• Most common causes when identified: spontaneous bacterial peritonitis (38%), peritoneal carcinomatosis (28%), nephrotic syndrome (17%) 5
• Recommend repeat paracentesis, as 73% convert to high SAAG on repeat testing 5

SAAG Has Replaced Exudate/Transudate Classification

• SAAG is superior to the older exudate/transudate system 2, 6, 7
• SAAG correctly identifies cause in 97% of cases vs. 83% for exudate/transudate 6

Additional Testing Based on Clinical Context

• PMN count: Always check to rule out spontaneous bacterial peritonitis (>250 cells/mm³) 1, 3
• Culture: Inoculate blood culture bottles at bedside if infection suspected 1, 3
• Cytology: Order only when malignancy suspected (sensitivity is limited) 1, 3
• Amylase: Check only when pancreatic origin suspected 1, 3
• Never order serum CA-125: Nonspecifically elevated in all ascites, leads to unnecessary referrals and potentially fatal surgeries 3

Rare Exception: Low SAAG in Heart Failure

• Heart failure typically causes high SAAG, but rare cases present with low SAAG 8
• Consider triphasic abdominal CT to confirm portal hypertension when clinical suspicion is high despite low SAAG 8