What is the significance of SAAG (Serum-Ascites Albumin Gradient) values in patients presenting with ascites?

SAAG Values: Clinical Significance in Ascites Evaluation

Primary Diagnostic Function

The SAAG (Serum-Ascites Albumin Gradient) is calculated by subtracting ascitic fluid albumin from serum albumin measured on the same day, and serves as the single most accurate test to distinguish portal hypertension-related ascites (SAAG ≥1.1 g/dL) from non-portal hypertension causes (SAAG <1.1 g/dL) with approximately 97% accuracy. 1, 2, 3

Calculation Method

• Measure serum albumin and ascitic fluid albumin on the same day 1, 3
• Subtract the ascitic fluid albumin value from the serum albumin value 1, 3
• The resulting number is the SAAG 3

Interpretation of SAAG Values

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

A SAAG ≥1.1 g/dL indicates portal hypertension with 97% accuracy and predicts response to sodium restriction and diuretics. 1, 2, 3

Common causes include:

• Liver cirrhosis 1, 2
• Cardiac ascites 1, 2
• Hepatic vein thrombosis (Budd-Chiari syndrome) 1, 2, 3
• Sinusoidal obstruction syndrome (veno-occlusive disease) 1, 2, 3

Low SAAG (<1.1 g/dL): Non-Portal Hypertension Causes

A SAAG <1.1 g/dL indicates non-portal hypertension etiology and predicts that patients will NOT respond to sodium restriction and diuretics (except nephrotic syndrome). 2, 3, 4

Common causes include:

• Peritoneal carcinomatosis 2, 4
• Tuberculous peritonitis 1, 2, 4
• Nephrotic syndrome 2, 3, 4
• Pancreatic ascites 2

Refining the Diagnosis: Adding Ascitic Fluid Protein

When SAAG is ≥1.1 g/dL, measure ascitic fluid total protein to distinguish cardiac from cirrhotic ascites: 2, 3

• High SAAG (≥1.1 g/dL) + High protein (>2.5 g/dL) = Cardiac ascites 2, 3
• High SAAG (≥1.1 g/dL) + Low protein (<2.5 g/dL) = Cirrhotic ascites 2, 3

When SAAG is <1.1 g/dL with high protein (>2.5 g/dL), suspect peritoneal tuberculosis or peritoneal carcinomatosis and proceed immediately to cytology, mycobacterial cultures, and consider laparoscopy with biopsy. 4

Direct Treatment Implications

For High SAAG Ascites (≥1.1 g/dL):

• Initiate dietary sodium restriction to 2000 mg/day (88 mmol/day) 2
• Start oral diuretics: spironolactone 100 mg daily plus furosemide 40 mg daily 2
• Treat underlying liver disease (e.g., alcohol cessation for alcoholic cirrhosis) 2, 3
• Consider large-volume paracentesis for tense ascites with albumin replacement at 8g per liter removed 2

For Low SAAG Ascites (<1.1 g/dL):

• Do NOT use sodium restriction and diuretics as primary therapy (exception: nephrotic syndrome may respond) 3, 4
• Direct treatment toward the underlying disorder 3, 4
• Order additional testing based on clinical suspicion: cytology for malignancy, mycobacterial cultures for tuberculosis 1, 4

Critical Pitfalls and Caveats

Mixed Ascites

Approximately 5% of patients have two or more causes of ascites simultaneously. 2, 3, 4 When portal hypertension coexists with a second cause (e.g., cirrhosis plus peritoneal carcinomatosis), the SAAG remains ≥1.1 g/dL because portal hypertension dominates the gradient. 2, 3, 4

Low SAAG in Known Cirrhosis

In patients with established cirrhosis who develop low SAAG ascites, only 38% have an identifiable non-portal hypertension cause. 5 The most common identifiable causes are spontaneous bacterial peritonitis (38%), peritoneal carcinomatosis (28%), and nephrotic syndrome (17%). 5 Importantly, 73% of cirrhotic patients with low SAAG who undergo repeat paracentesis convert to high SAAG, suggesting measurement error or transient conditions. 5 Therefore, repeat paracentesis is recommended in cirrhotic patients with unexpectedly low SAAG. 5

Infection Risk Assessment

**Ascitic fluid total protein <1.5 g/dL is a major risk factor for spontaneous bacterial peritonitis and may warrant prophylactic antibiotics in cirrhotic patients.** 4 Always measure ascitic fluid neutrophil count; >250 cells/μL indicates spontaneous bacterial peritonitis requiring immediate antibiotics. 4

Diagnostic Testing to Avoid

Never order serum CA-125 in patients with ascites—it is nonspecifically elevated by mesothelial cell pressure from any cause of ascites and leads to unnecessary gynecologic referrals and potentially harmful surgeries. 4

Prognostic Significance

Development of ascites in cirrhotic patients indicates poor prognosis with approximately 20% mortality in the first year, warranting liver transplantation evaluation. 2, 4

Initial Workup Algorithm

For all new-onset ascites, obtain: 2, 3, 4

1. Ascitic fluid cell count with differential
2. Ascitic fluid albumin (with simultaneous serum albumin for SAAG calculation)
3. Ascitic fluid total protein
4. If infection suspected: culture fluid at bedside in blood culture bottles before antibiotics 2, 3, 4
5. Additional tests based on clinical suspicion: cytology, amylase, mycobacterial studies 1, 4