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Ascites — Sleisenger and Fordtran's Gastrointestinal and Liver Disease (Chapter 93)

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Definition and Epidemiology

• Impaired health-related quality of life
• Increased risk of SBP, hyponatremia, and AKI
• Poor survival: 5-year survival ~30% with ascites vs. ~80% in compensated cirrhosis

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Pathogenesis of Ascites in Cirrhosis

• RAAS (renin-angiotensin-aldosterone system)
• SNS (sympathetic nervous system)

1. Sodium Retention and ECF Volume Expansion

• Earliest and most frequent renal abnormality in cirrhosis
• Sodium is retained isosmotically with water
• Ascites develops when urinary sodium excretion < dietary sodium intake
• Degree of sodium retention varies widely: patients with urine Na <10 mEq/day have marked retention and worse prognosis
• Goal of pharmacologic therapy: achieve negative sodium balance

2. Portal Hypertension

• Portal hypertension triggers splanchnic vasodilation
• Leads to underfilling of the systemic circulation
• Activates neurohumoral systems (RAAS, SNS, ADH), causing renal sodium and water retention

3. Systemic Circulatory Dysfunction

• Splanchnic arterial vasodilation causes "underfilling" of the effective arterial blood volume
• Results in:
  • Impaired ability to excrete sodium
  • Impaired ability to excrete solute-free water (causing dilutional hyponatremia)
  • Reduced GFR via renal vasoconstriction (leading to hepatorenal syndrome in advanced disease)
• Chronological progression: sodium retention (earliest) → dilutional hyponatremia → HRS (most advanced)

4. Systemic Inflammation

• Chronic systemic inflammatory state further impairs circulatory function
• Contributes to kidney dysfunction and multiorgan failure in advanced cirrhosis

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Diagnosis

Clinical Assessment

• Medical history and physical examination
• Standard blood tests
• Abdominal ultrasound

Laboratory Tests

• Urine sodium excretion: Predicts diuretic response. Patients with urine Na ≥10 mEq/day respond better to lower diuretic doses. Urine Na <10 mEq/day = median survival only 1.5 years vs. 4.5 years with ≥10 mEq/day.

Abdominal Ultrasound

• First-line imaging for all patients with first-episode ascites
• Evaluates liver parenchyma, portal vein and suprahepatic vein patency, and rules out liver tumor
• Also indicated for known ascites with unexplained loss of treatment response

Ascitic Fluid Analysis

• All patients with first episode of grade 2 or 3 ascites
• All patients with ascites admitted to hospital for any intercurrent complication

• SAAG = serum albumin - ascitic fluid albumin (subtraction, NOT a ratio)
• SAAG ≥1.1 g/dL = portal hypertension (accuracy ~97%) — includes cirrhosis, cardiac ascites
• SAAG <1.1 g/dL = non-portal hypertension cause (peritoneal carcinomatosis, TB peritonitis, pancreatic ascites)

• Suspected secondary bacterial peritonitis: ascitic glucose (near 0 mg/dL in secondary peritonitis), LDH (several-fold above serum), Gram stain (polymicrobial)
• Suspected malignancy: cytology (positive for peritoneal tumor, negative if tumor confined to liver)
• Suspected TB: mycobacterial culture
• Suspected pancreatic ascites: amylase/lipase

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Grading of Ascites

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Differential Diagnosis

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Complications of Ascites

1. Spontaneous Bacterial Peritonitis (SBP) - most important (see below)
2. Refractory ascites - 10% of patients develop this; median survival ~6 months
3. Hepatorenal Syndrome (HRS)
4. Hepatic hydrothorax - accumulation of fluid in pleural space via diaphragmatic defects; median survival ~1 year; MELD underestimates prognosis
5. Abdominal wall hernias (umbilical/inguinal) - occur in up to 20% of refractory ascites patients; risks: incarceration, perforation

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Management of Ascites in Cirrhosis

Grade 1 Ascites

• No treatment recommended (insufficient data on natural history)

Grade 2 (Moderate) Ascites

• Managed in outpatient setting
• Most have urine Na >20 mEq/L at baseline
• Dietary sodium restriction: 80-120 mEq/day (4.6-6.9 g salt/day) - more stringent restriction is poorly tolerated and may worsen malnutrition
• Diuretics (first-line):
  • Spironolactone (anti-mineralocorticoid): 100 mg/day, can increase to 400 mg/day
  • Furosemide (loop diuretic): often combined, starting at 40 mg/day, up to 160 mg/day
  • Combination preferred: maintains normokalemia; spironolactone:furosemide ratio 100:40 maintained throughout
• Response target: weight loss of 0.5 kg/day (no edema) or 1 kg/day (with edema)
• Monitor: serum creatinine, Na, K during therapy

Grade 3 (Tense) Ascites

• Large-Volume Paracentesis (LVP) is first-line treatment
• Must be accompanied by IV albumin infusion to prevent post-paracentesis circulatory dysfunction (PPCD):
  • 6-8 g albumin per liter of ascites removed when >5 L removed
  • For <5 L: alternative plasma expanders may be acceptable, but albumin preferred
• After LVP: restart diuretic therapy + sodium restriction to prevent recurrence

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Refractory Ascites

• Maximum diuretic doses, OR
• Diuretic-related complication preventing effective dosing

• Diuretic-resistant: No response to spironolactone 400 mg/day + furosemide 160 mg/day with Na restriction
• Diuretic-intractable: Diuretic-induced complications preclude effective dosing

1. LVP + Albumin

• First-line for refractory ascites
• Repeated as needed; patient typically requires paracentesis every 2-4 weeks

2. Diuretics in Refractory Ascites

• Should generally be stopped once refractory ascites develops to prevent adverse events

3. TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• Connects intrahepatic portal branch to hepatic vein outflow → decompresses portal system
• Improves effective blood volume and renal hemodynamics → increases urinary Na excretion
• Evidence: 6 RCTs + 7 meta-analyses show TIPS > LVP for control of recurrent/refractory ascites
• Survival benefit: TIPS improves survival in recurrent ascites but NOT in refractory ascites
• Covered stents preferred (reduce TIPS dysfunction and hepatic encephalopathy)
• HE risk: up to 50% with uncovered stents; reduced with covered stents

• Serum bilirubin >3 mg/dL
• Platelet count <75,000/mm³ (especially <20,000/mm³)
• Grade >2 or chronic hepatic encephalopathy
• Multiple hepatic cysts
• Unrelieved biliary obstruction
• Active infection
• Progressive renal failure
• Severe systemic or diastolic cardiac dysfunction
• Pulmonary hypertension

4. Hepatic Hydrothorax Management

• Thoracentesis for diagnosis and symptomatic relief
• Same medical treatment as ascites (Na restriction + diuretics)
• Chest tube drainage contraindicated (risk of complications)
• TIPS can be considered in selected cases
• LT is the definitive treatment

Contraindicated Drugs in Cirrhotic Ascites

• NSAIDs: Cause renal vasoconstriction and sodium retention; precipitate AKI and HRS
• ACE inhibitors / ARBs: Cause hypotension and AKI in cirrhosis
• Alpha-1 adrenergic blockers (e.g., prazosin): Worsen circulatory dysfunction
• Aminoglycosides: Nephrotoxic

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Spontaneous Bacterial Peritonitis (SBP)

Pathogenesis

Diagnosis

• PMN count >250/mm³ in ascitic fluid = diagnostic of SBP
• Culture should be performed (monomicrobial = SBP; polymicrobial = suspect secondary bacterial peritonitis)
• Most common organisms: Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae

Treatment

• Cefotaxime 2g IV q8h x 5 days (antibiotic of choice)
• IV albumin 1.5 g/kg at diagnosis + 1 g/kg on day 3 → prevents HRS and reduces mortality

Prophylaxis

• Primary prophylaxis: Indicated when ascitic protein <1.5 g/dL AND (serum creatinine ≥1.2 mg/dL OR BUN ≥25 mg/dL OR serum Na ≤130 mEq/L OR Child-Pugh ≥9 + bilirubin ≥3 mg/dL)
• Secondary prophylaxis (after first SBP episode): Norfloxacin 400 mg/day indefinitely (or ciprofloxacin/trimethoprim-sulfamethoxazole)
• Short-term prophylaxis (GI hemorrhage): IV ceftriaxone 1g/day x 7 days

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