What is the recommended medication regimen for an adult with compensated or decompensated cirrhosis to treat the underlying etiology, prevent portal‑hypertensive complications, and manage ascites, hepatic encephalopathy, and infection?

Comprehensive Medication Regimen for Cirrhosis Management

The cornerstone of cirrhosis management is aggressive treatment of the underlying etiology—complete alcohol abstinence, antiviral therapy for viral hepatitis, or immunosuppression for autoimmune disease—as this single intervention most effectively prevents further decompensation and improves survival. 1

Treat the Underlying Cause First

• For alcoholic cirrhosis: Mandate complete and permanent alcohol cessation; this can lead to "re-compensation" and excellent long-term outcomes in some patients. 1
• For HBV-related cirrhosis: Initiate entecavir 1 mg daily or tenofovir as first-line therapy if HBV DNA ≥2,000 IU/mL, regardless of ALT levels; these agents have potent antiviral efficacy and high genetic barrier to resistance. 1
• For HCV-related cirrhosis: Direct-acting antivirals improve liver function and reduce portal hypertension, though effects are not universal. 1
• For autoimmune hepatitis: Immunosuppressive therapy shows beneficial effects even in decompensated cirrhosis. 1
• Critical caveat: Interferon-α is absolutely contraindicated in decompensated cirrhosis due to risk of infection and hepatic failure. 1

Ascites Management: Stepwise Medication Algorithm

Grade 1 Ascites (Detectable Only by Imaging)

• Sodium restriction to <5 g/day (88 mmol/day) is the primary intervention; more stringent restriction worsens malnutrition. 2, 1
• No diuretics needed yet; focus on treating underlying disease. 1
• Discontinue NSAIDs, ACE inhibitors, and angiotensin receptor blockers immediately. 1

Grade 2 Ascites (Moderate, Visible on Inspection)

• Start spironolactone 100 mg once daily as first-line monotherapy. 2, 1
• If weight loss <2 kg/week: Increase spironolactone by 100 mg every 72 hours, up to maximum 400 mg/day. 2, 1
• Add furosemide 40 mg/day when spironolactone alone is insufficient or hyperkalemia develops (K+ >5.5 mEq/L); titrate by 40 mg increments to maximum 160 mg/day. 2, 1
• For recurrent or long-standing ascites: Start combination therapy (spironolactone + furosemide) from the outset to achieve faster natriuresis and lower hyperkalemia risk. 1
• Target weight loss: 0.5 kg/day without peripheral edema or 1 kg/day with edema. 1
• Monitor weekly: Serum creatinine, sodium, and potassium during the first month. 2, 1

Grade 3 Ascites (Massive/Tense)

• Perform therapeutic paracentesis first to relieve symptoms, then initiate sodium restriction and diuretic therapy. 2, 1
• Albumin replacement: Administer 8 g albumin per liter of ascites removed (approximately 100 mL of 20% albumin for every 3 L removed) when removing >5 L. 2, 1
• For <5 L removed: Albumin can be considered in patients with acute-on-chronic liver failure or high risk of post-paracentesis acute kidney injury. 2

Hyponatremia Management During Diuretic Therapy

Serum Sodium	Creatinine	Action
126–135 mmol/L	Normal	Continue diuretics; monitor closely; no fluid restriction [1]
121–125 mmol/L	Normal	Stop diuretics or adopt cautious approach [1]
121–125 mmol/L	Elevated (>150 µmol/L)	Stop diuretics; give volume expansion [1]
<120 mmol/L	Any	Stop diuretics; volume expansion with colloid/saline; avoid Na+ increase >12 mmol/L per 24h [1]

• Fluid restriction is unnecessary unless serum sodium <120–125 mmol/L. 2, 1

Refractory Ascites

• Definition: Ascites recurring at least three times within 12 months despite dietary sodium restriction and adequate diuretic dosage. 2
• Options: Serial large-volume paracentesis, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation evaluation. 2
• TIPS should be considered but use caution if age >70 years, bilirubin >50 µmol/L, platelets <75×10⁹/L, MELD ≥18, current hepatic encephalopathy, active infection, or hepatorenal syndrome. 2
• Palliative care referral should be offered to patients not undergoing transplant evaluation. 2

Spontaneous Bacterial Peritonitis (SBP) Prevention and Treatment

Diagnosis

• Perform diagnostic paracentesis without delay in all patients with new-onset grade 2–3 ascites or any hospitalized patient with cirrhosis complications. 2, 1
• Inoculate at least 10 mL ascitic fluid into blood culture bottles at bedside to enhance sensitivity. 2
• SBP diagnosis: Ascitic neutrophil count >250 cells/µL. 2, 1

Treatment and Prophylaxis

• For active SBP: Administer albumin 1.5 g/kg within 6 hours of diagnosis, followed by 1 g/kg on day 3, especially if serum creatinine is elevated or rising. 2
• Secondary prophylaxis after SBP: Norfloxacin 400 mg orally once daily indefinitely. 3, 4
• Primary prophylaxis: Consider norfloxacin 400 mg daily in patients with ascitic fluid protein <1.5 g/dL. 4
• For variceal bleeding with ascites: Ceftriaxone 1 g IV every 24 hours for up to 7 days in decompensated cirrhosis or quinolone-resistant settings; otherwise norfloxacin 400 mg twice daily. 1, 3
• All patients with SBP should be evaluated for liver transplantation. 1

Hepatic Encephalopathy (HE) Management

Diagnosis

• Clinical assessment is the cornerstone: Evaluate mental status, vigilance, attention, and spatial-temporal orientation. 1
• Animal Naming Test: <20 animals named in 1 minute suggests covert HE. 1
• Ammonia levels: Measure only when HE diagnosis is uncertain; normal value argues against HE, but elevated value does not confirm it. 1

Treatment

• First-line: Lactulose titrated to 2–3 soft bowel movements daily; reduces mortality (8.5% vs 14% placebo) and recurrent overt HE (25.5% vs 46.8%). 5
• Second-line: Add rifaximin 550 mg twice daily for persistent or recurrent HE episodes. 3, 4
• Identify and treat precipitants: GI bleeding, infection, dehydration, constipation, electrolyte disturbances. 1
• Discontinue benzodiazepines immediately; they are contraindicated in decompensated cirrhosis. 1
• Limit proton pump inhibitors to validated indications only, as they increase SBP risk. 4

Portal Hypertension and Variceal Bleeding Prevention

Compensated Cirrhosis with Clinically Significant Portal Hypertension (CSPH)

• Non-selective beta-blockers (NSBBs) prevent decompensation: In patients with CSPH (HVPG ≥10 mmHg) without high-risk varices, NSBBs reduce cirrhosis decompensation (ascites, bleeding, or HE) or death from 27% to 16%. 2
• Carvedilol or propranolol titrated according to heart rate are preferred agents. 2
• HVPG response matters: "Chronic" HVPG response (>10% reduction or <12 mmHg) predicts lower rates of ascites (27% vs 89%), variceal bleeding (5% vs 17%), and improved mortality. 2

Screening and Primary Prophylaxis

• Perform upper endoscopy to screen for varices in all patients with compensated cirrhosis. 1
• If large varices present: Initiate NSBB or endoscopic band ligation. 2
• If CSPH present but no varices: Start NSBB unless contraindicated. 2
• If liver stiffness ≥20 kPa and/or platelets <150×10⁹/L: Perform upper endoscopy to screen for varices. 2

Caution with NSBBs in Refractory Ascites

• Refractory ascites is not an absolute contraindication to NSBBs. 2
• Monitor closely: Dose reduction or discontinuation may be appropriate if hypotension (mean arterial pressure <65 mmHg) or acute/progressive renal dysfunction develops. 2

Hepatorenal Syndrome (HRS)

• First-line treatment: Terlipressin plus albumin; improves reversal rate from 18% to 39%. 5
• Albumin dosing: 1 g/kg on day 1 (maximum 100 g), then 20–40 g/day. 5

Medications to Absolutely Avoid in Cirrhosis

• NSAIDs are absolutely contraindicated: They reduce urinary sodium excretion, precipitate renal dysfunction, and convert diuretic-sensitive ascites to refractory ascites. 2, 1, 6
• Metformin: Can be used in compensated cirrhosis with preserved renal function (GFR >30 mL/min) but should not be used in decompensated cirrhosis due to lactic acidosis risk. 2, 3
• Sulfonylureas: Avoid in hepatic decompensation due to hypoglycemia risk. 2
• Benzodiazepines: Contraindicated in decompensated cirrhosis; discontinue immediately if prescribed. 1
• ACE inhibitors and angiotensin receptor blockers: Discontinue in patients with ascites. 1

Medications Safe to Use with Caution

Diabetes Management

• Compensated cirrhosis (Child-Pugh A): GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) and SGLT2 inhibitors (empagliflozin, dapagliflozin) can be used. 2
• Child-Pugh B cirrhosis: SGLT2 inhibitors can be used. 2
• Decompensated cirrhosis: Insulin is the only evidence-based option; do not use HbA1c for monitoring. 1

Cardiovascular Management

• Statins can be used in compensated cirrhosis according to cardiovascular risk guidelines; they may reduce portal hypertension and improve survival, though this requires further validation. 2, 3

Pain Management

• Acetaminophen (paracetamol) can be used safely at doses ≤2–3 g/day for short durations; it is first-line for pain. 6

Monitoring and Follow-Up

• Check serum creatinine, sodium, and potassium at least weekly during the first month of diuretic treatment. 1
• Perform diagnostic paracentesis for any new or worsening ascites, fever, abdominal pain, altered mental status, or unexplained deterioration. 1
• Screen for hepatocellular carcinoma every 6 months with ultrasound ± AFP in all cirrhotic patients. 5
• Evaluate all patients with decompensated cirrhosis for liver transplantation. 1, 3

Common Pitfalls to Avoid

• Do not routinely restrict fluids in ascites; restrict only when serum sodium <120–125 mmol/L. 2, 1
• Do not prescribe bed rest; excessive inactivity causes muscle atrophy and sarcopenia. 1
• Do not use ammonia levels to diagnose or monitor HE; HE remains a clinical diagnosis. 1
• Do not use rifaximin as an alternative to norfloxacin for SBP prophylaxis; it is not validated for this indication. 4
• Do not delay paracentesis due to coagulopathy; severe hemorrhage occurs in only 0.2–2.2% of procedures. 1
• Do not use proton pump inhibitors liberally; they increase SBP risk and should be limited to validated indications. 4, 6