What is the recommended approach to managing a patient with cirrhosis?

Managing Cirrhosis: A Comprehensive Evidence-Based Approach

The cornerstone of cirrhosis management is aggressive treatment of the underlying etiology combined with systematic prevention and management of complications, with all decompensated patients requiring immediate liver transplant evaluation. 1

1. Treat the Underlying Cause First

Etiological therapy is the single most important intervention to prevent decompensation and improve survival. 1 The management paradigm has shifted from reactive complication treatment to proactive disease modification while patients remain compensated. 1

Specific Etiological Treatments:

• Alcohol-related cirrhosis: Complete and permanent alcohol cessation is mandatory and can lead to "re-compensation" with excellent long-term outcomes in some patients. 1

• Hepatitis B: Start antiviral therapy immediately when HBV DNA is detectable by PCR, regardless of ALT level or viral load. 1 Use entecavir 1 mg daily (not 0.5 mg) or tenofovir as first-line agents due to potent antiviral activity and high genetic barrier to resistance. 1 Peginterferon-α is absolutely contraindicated in decompensated cirrhosis due to risk of hepatic failure, infection, and death. 1

• Hepatitis C: Direct-acting antivirals improve liver function and reduce portal hypertension, though benefits are not universal. 1

• Autoimmune hepatitis: Immunosuppressive therapy shows clear benefits even in decompensated disease. 1

2. Ascites Management: A Staged Approach

Grade 1 Ascites (Detectable Only by Imaging):

• Restrict dietary sodium to <5 g/day (87-113 mmol/day); this translates to a no-added-salt diet with avoidance of precooked meals. 2
• Stricter sodium restriction is not recommended as it worsens malnutrition. 2, 1
• Provide nutritional counseling on sodium content. 2

Grade 2 Ascites (Moderate, Visible on Inspection):

• Start spironolactone 100 mg once daily as monotherapy for first presentation. 2
• If weight loss is <2 kg/week, increase spironolactone by 100 mg every 72 hours up to maximum 400 mg/day. 2
• Add furosemide 40 mg/day when spironolactone alone is insufficient or hyperkalemia develops (K+ >5.5 mmol/L); titrate in 40 mg increments to maximum 160 mg/day. 2, 1
• For recurrent or long-standing ascites, begin combination therapy (spironolactone + furosemide) from the outset to achieve faster natriuresis. 2

Grade 3 Ascites (Massive/Tense):

• Perform therapeutic paracentesis first, then initiate sodium restriction and diuretic therapy. 2, 1
• Ultrasound guidance should be considered when available to reduce adverse events. 2
• Routine measurement of prothrombin time and platelet count before paracentesis is not recommended. 2

Albumin Replacement After Large-Volume Paracentesis:

• Infuse albumin (20% or 25% solution) at 8 g/L of ascites removed when >5 L are extracted. 2
• For <5 L removed, consider albumin in patients with acute-on-chronic liver failure or high risk of post-paracentesis acute kidney injury. 2

Monitoring During Diuretic Therapy:

• Check serum creatinine, sodium, and potassium at least weekly during the first month. 2, 1
• Target weight loss of 0.5 kg/day without peripheral edema or 1 kg/day with edema. 1
• Almost half of patients on diuretics experience adverse events requiring dose reduction or discontinuation. 2

Hyponatremia Management Algorithm:

Serum Sodium	Action
126-135 mmol/L	Continue diuretics; monitor closely [1]
120-125 mmol/L	Stop diuretics or use cautiously; fluid restriction to 1-1.5 L/day [2,1]
<120 mmol/L	Stop diuretics; expand plasma volume with normal saline [2,1]

• Hypertonic saline (3%) should be reserved for severely symptomatic acute hyponatremia, with slow correction. 2

Refractory Ascites:

• Options include serial large-volume paracentesis, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation. 2, 1
• Midodrine may be considered on a case-by-case basis. 2
• Patients requiring paracentesis more frequently than every 2 weeks likely have poor dietary compliance. 1
• Palliative care referral should be offered to non-transplant candidates. 1

3. Spontaneous Bacterial Peritonitis (SBP) Prevention and Management

Diagnostic Approach:

• Perform diagnostic paracentesis without delay in any cirrhotic patient with ascites on hospital admission or clinical deterioration. 2, 3
• Send ascitic fluid for: cell count with differential (neutrophil count >250/mm³ confirms SBP), culture with bedside inoculation into blood culture bottles, total protein, and serum-ascites albumin gradient. 2, 3

Treatment:

• In patients with SBP and increased or rising serum creatinine, infuse albumin 1.5 g/kg within 6 hours of diagnosis, followed by 1 g/kg on day 3. 2
• Start empirical antibiotics immediately; ceftriaxone 1 g daily is first-line, covering approximately 95% of flora. 3
• Cefotaxime has been widely studied, but antibiotic choice should be guided by local resistance patterns. 2

Prophylaxis:

• Secondary prophylaxis: Patients who have recovered from SBP should receive norfloxacin 400 mg once daily, ciprofloxacin 500 mg once daily, or co-trimoxazole (800 mg sulfamethoxazole/160 mg trimethoprim daily). 2
• Primary prophylaxis: Offer to high-risk patients with ascitic protein <1.5 g/dL, guided by local resistance patterns. 2
• Patients with gastrointestinal bleeding and ascites should receive prophylactic antibiotics. 2, 1

4. Acute Kidney Injury (AKI) Management in Cirrhosis

Stage 1 AKI:

• Review all medications immediately: Withdraw diuretics, nephrotoxic drugs, vasodilators, and NSAIDs. 2
• Provide plasma volume expansion in clinically suspected hypovolemia with crystalloids, albumin, or blood (if AKI from GI bleeding). 2
• Promptly recognize and treat bacterial infections when diagnosed or strongly suspected. 2
• Monitor closely; assess serum creatinine every 2-4 days during hospitalization and every 2-4 weeks for first 6 months after discharge. 2

Stage 2 and 3 AKI:

• Withdraw diuretics (if not already done) and expand plasma volume with albumin 1 g/kg for 2 consecutive days. 2
• If criteria for hepatorenal syndrome are met, initiate vasoconstrictors and albumin. 2

5. Hepatic Encephalopathy Management

Identify and Treat Precipitating Factors:

• Look for: constipation, infection, GI bleeding, certain medications, electrolyte imbalances, and medication noncompliance. 4, 5
• Serum sodium <130 mmol/L is an independent risk factor for hepatic encephalopathy. 1
• Discontinue benzodiazepines immediately; they are contraindicated in decompensated cirrhosis. 1
• Limit proton-pump inhibitor use to validated indications only. 1

Pharmacologic Treatment:

• Initiate lactulose 30-45 mL every 1-2 hours until patient has at least 2 bowel movements, then titrate to achieve 2-3 soft stools daily. 3, 6
• Lactulose reduces mortality (8.5% vs 14% with placebo) and recurrent overt hepatic encephalopathy (25.5% vs 46.8%). 6
• Add rifaximin 550 mg twice daily for persistent or recurrent episodes. 1, 3
• Combination therapy improves recovery (76% vs 44%) and shortens hospital stays. 3

Diagnostic Considerations:

• Hepatic encephalopathy remains a clinical diagnosis; the Animal Naming Test (<20 animals in 1 minute) suggests covert hepatic encephalopathy. 1
• Blood ammonia measurement is only useful when diagnosis is uncertain; a normal value argues against hepatic encephalopathy, but an elevated value does not confirm it. 1

6. Variceal Bleeding Prevention

• Non-selective beta-blockers (carvedilol or propranolol) reduce the composite outcome of decompensation or death from 27% to 16% in patients with clinically significant portal hypertension. 1, 6
• In a 3-year trial, non-selective beta-blockers reduced decompensation or death compared with placebo (16% vs 27%). 6
• Screening endoscopy should be performed to assess for varices requiring prophylaxis. 1
• Prophylactic band ligation is standard of care for varices. 1

Caution with Beta-Blockers:

• Use with caution in patients with severe or refractory ascites. 1
• Reduce or stop if mean arterial pressure falls <65 mmHg or acute/progressive renal dysfunction develops. 1

7. Medications to Absolutely Avoid

• NSAIDs are absolutely contraindicated in cirrhosis. 2, 1 They reduce urinary sodium excretion, precipitate renal dysfunction, and convert diuretic-sensitive ascites to refractory ascites. 2, 1
• Discontinue ACE inhibitors and angiotensin receptor blockers. 1, 3
• Metformin is contraindicated in decompensated cirrhosis due to lactic acidosis risk. 1
• Sulfonylureas should be avoided in hepatic decompensation due to hypoglycemia risk. 1

8. Medications Safe with Caution

• Compensated cirrhosis (Child-Pugh A): GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) and SGLT2 inhibitors (empagliflozin, dapagliflozin) are acceptable. 1
• Child-Pugh B: SGLT2 inhibitors may be used. 1
• Statins: Can be prescribed in compensated cirrhosis according to cardiovascular-risk guidelines; they may also lower portal pressure and improve survival. 1

9. Hepatocellular Carcinoma Screening

• Perform ultrasound screening every 6 months for all patients with cirrhosis. 4, 5
• Approximately 1-4% of patients with cirrhosis develop hepatocellular carcinoma each year, with 5-year survival of approximately 20%. 6

10. Gastroenterology Referral Indications

• Any decompensation event (ascites, variceal bleeding, hepatic encephalopathy). 1
• Refractory ascites not responding to maximum diuretic therapy. 1
• Need for TIPS placement. 1
• All patients with decompensated cirrhosis should be evaluated for liver transplantation immediately. 1, 3

11. Monitoring Schedule

• Liver function tests every 1-3 months. 1
• In HBV-related disease, serum HBV DNA (real-time PCR) and HBeAg status every 2-6 months. 1

12. Common Pitfalls to Avoid

• Do not impose routine fluid restriction; restrict fluids only when serum sodium is <120-125 mmol/L. 2, 1
• Bed rest is not recommended; excessive bed rest causes muscle atrophy and sarcopenia. 1
• Do not rely on ammonia levels to diagnose or monitor hepatic encephalopathy; it remains a clinical diagnosis. 1
• Do not use reverse MDRD formula to estimate baseline creatinine in cirrhotic patients; it is inaccurate, particularly in those with ascites. 2
• Patients can be managed outpatient unless complicated by bleeding, encephalopathy, infection, hypotension, or liver cancer. 1

13. Prognosis

• Without liver transplantation, median survival with decompensated cirrhosis is approximately 1 year. 3
• Median survival after onset of hepatic encephalopathy is 0.92 years and after ascites is 1.1 years. 6
• Among patients with ascites, annual incidence of spontaneous bacterial peritonitis is 11% and hepatorenal syndrome is 8%; the latter is associated with median survival of less than 2 weeks. 6