What is the treatment for a patient with portal hypertension, likely due to underlying liver disease such as cirrhosis?

Treatment for Portal Hypertension in Cirrhosis

The treatment of portal hypertension must be stratified by disease stage, with etiological therapy as the foundation for all patients, non-selective beta-blockers (NSBBs) for those with clinically significant portal hypertension and varices, and transjugular intrahepatic portosystemic shunt (TIPS) reserved for refractory complications. 1, 2

Stage-Based Treatment Algorithm

Stage 1: Mild Portal Hypertension (HVPG 5-10 mmHg)

Focus exclusively on treating the underlying liver disease—NSBBs are ineffective and should not be initiated at this stage. 1, 3

• Eliminate etiological factors: alcohol cessation, antiviral therapy for hepatitis B/C, weight loss for NAFLD, immunosuppression for autoimmune hepatitis 1, 3
• Do NOT start NSBBs: The hyperdynamic circulatory state is not fully developed, making NSBBs mostly ineffective and potentially harmful with increased adverse events 1
• Surveillance: Repeat endoscopy every 2-3 years if compensated, or when decompensation occurs 1

Stage 2: Clinically Significant Portal Hypertension Without Varices (HVPG ≥10 mmHg)

Continue aggressive etiological treatment but do NOT initiate NSBBs for "preprimary prophylaxis" of varix formation. 1

• A large multicenter trial showed timolol provided no benefit over placebo in preventing varices (39% vs 40%, P=0.89) but caused significantly more serious adverse events (18% vs 6%, P=0.006) 1
• Surveillance: Endoscopy every 2 years with ongoing liver injury, or every 3 years if liver injury is quiescent 1

Stage 3: Small Varices (F1)

NSBBs or carvedilol may be considered only in high-risk patients with small varices. 1, 2

• High-risk criteria: Child-Pugh B/C cirrhosis OR red color signs on varices 1, 2
• Low-risk patients: Surveillance endoscopy every 1-2 years; NSBBs optional but not mandatory 1
• Carvedilol option: May delay progression to large varices (20.6% vs 38.6% with placebo at 24 months, P=0.04) due to additional alpha-1 blockade reducing intrahepatic resistance 1

Stage 4: Large Varices (F2/F3) or High-Risk Small Varices

Initiate NSBBs immediately—this is the cornerstone of primary prophylaxis. 1, 2, 4

First-Line NSBB Therapy:

• Carvedilol 12.5 mg/day: Superior to traditional NSBBs, achieving hemodynamic response in 50-75% of patients versus 46% with propranolol/nadolol 2, 3
• Alternative traditional NSBBs: Propranolol 40 mg twice daily (titrate to 80 mg twice daily) or nadolol, targeting 25% heart rate reduction or resting HR of 55 bpm 2, 4
• Target hemodynamic response: HVPG reduction to <12 mmHg or >10-20% decrease from baseline protects against acute variceal bleeding 2, 5

Alternative: Endoscopic Variceal Ligation (EVL)

• EVL is equivalent to NSBBs for primary prophylaxis (RR 0.86,95% CI 0.55-1.35) 1
• NSBBs are preferred as they reduce portal pressure globally and prevent other complications beyond bleeding 4

Management of Specific Complications

Ascites

Sodium restriction (2000 mg/day) plus oral diuretics are the mainstays of treatment. 1

• Initial diuretic regimen: Spironolactone 100 mg + furosemide 40 mg once daily in the morning 1, 6
• Fluid restriction is NOT necessary unless severe hyponatremia (<120-125 mmol/L) develops 1
• Monitor 24-hour urinary sodium: Goal >78 mmol/day (88 mmol intake - 10 mmol nonurinary losses) 1
• Albumin therapy: In selected patients, long-term albumin use reduces further decompensation and improves survival 7

Critical safety warning: In patients with refractory ascites and hypotension (systolic BP <90 mmHg or MAP <65 mmHg), NSBBs should be temporarily suspended or used with extreme caution 2, 3

Portal Hypertensive Gastropathy (Chronic Bleeding)

Manage with portal pressure-lowering strategies, not blood products. 1, 4

• Chronic setting: NSBBs (propranolol or nadolol) are recommended to reduce bleeding severity and mortality 1, 4
• Propranolol dosing: Start 40 mg twice daily, titrate to 80 mg twice daily or maximal tolerated dose 4
• Adjunctive therapy: Iron supplementation for iron-deficiency anemia; oral iron is usually sufficient 2, 4
• Refractory cases: Consider endoscopic argon plasma coagulation or TIPS 4

Acute Variceal Bleeding

Initiate vasoactive drugs immediately when variceal hemorrhage is suspected, before endoscopy. 2, 4, 3

Immediate Management Protocol:

1. Vasoactive drugs: Octreotide, somatostatin, or terlipressin—start immediately 2, 4, 3
2. Prophylactic antibiotics: Ceftriaxone 1 g IV daily (maximum 7 days) reduces mortality, infections, and rebleeding 2, 3
3. Restrictive transfusion strategy: Start transfusion at hemoglobin 7 g/dL with goal 7-9 g/dL—excessive transfusion paradoxically increases portal pressure 1, 2, 3
4. Endoscopy within 12 hours: Perform EVL once hemodynamically stable 2, 3
5. Continue vasoactive drugs 2-5 days post-endoscopy, then transition to oral NSBBs 2

Do NOT use tranexamic acid in active variceal bleeding—this is contraindicated. 2, 3

Do NOT routinely correct coagulation abnormalities before prophylactic band ligation in stable patients—this provides no benefit and is not recommended 2, 3

Refractory Complications

TIPS is strongly recommended for variceal bleeding refractory to endoscopic and medical therapy. 4, 3

TIPS Indications:

• Refractory variceal bleeding: Failure of endoscopic and pharmacological therapy 4, 3
• Early/preemptive TIPS: Consider within 72 hours in high-risk patients (Child-Pugh C or MELD ≥19) 2, 4, 3
• Refractory or recurrent ascites: Selected patients who fail medical management 4, 3

TIPS Contraindications:

• Bilirubin >50 μmol/L, platelets <75×10⁹, pre-existing encephalopathy, active infection, severe cardiac failure, severe pulmonary hypertension 4
• Hepatic encephalopathy affects approximately one-third of patients after TIPS and usually responds to medical therapy 4

Critical Safety Considerations

When to Suspend NSBBs:

• Acute bleeding with hypotension: Systolic BP <90 mmHg or MAP <65 mmHg 2, 3
• Refractory ascites with hypotension: Use extreme caution or suspend temporarily 2, 3

Absolute Contraindications to NSBBs:

• Severe bradycardia, heart block, severe asthma, decompensated heart failure 3

Blood Product Administration:

Administering large volumes of blood products paradoxically increases portal pressure and may worsen bleeding—use restrictive transfusion strategies 1, 2

Monitoring and Long-Term Management

• Hemodynamic response is usually sustained long-term (maintained in 81% of cases), primarily influenced by medication compliance and alcohol intake 5
• Responders have significantly better outcomes: Lower probability of developing ascites (P<0.001), encephalopathy (P=0.001), need for transplantation (P=0.002), and improved survival (P=0.029) 5
• HVPG monitoring can guide therapy when available, though not recommended routinely outside clinical trials 1

Definitive Treatment

Liver transplantation should be considered in all patients with decompensated cirrhosis—it is the most effective approach to reduce portal pressure and improve survival. 2, 3