What medications are used to treat patients with portal hypertension and liver cirrhosis?

Pharmacological Management of Portal Hypertension and Liver Cirrhosis

Non-selective beta-blockers (NSBBs) are the cornerstone of pharmacological treatment for portal hypertension in cirrhotic patients with varices, with carvedilol 12.5 mg/day as the preferred first-line agent due to superior portal pressure reduction compared to traditional NSBBs. 1

Stage-Based Treatment Algorithm

Stage 1: Mild Portal Hypertension (HVPG 5-10 mmHg, No Varices)

• Do not initiate NSBBs in patients with cirrhosis but no varices, as they fail to prevent varix formation and significantly increase serious adverse events (18% vs 6% with placebo, P=0.006) without benefit 2, 1
• Focus exclusively on treating the underlying liver disease: alcohol cessation, antiviral therapy for hepatitis B/C (tenofovir, direct-acting antivirals), weight loss for NAFLD, or immunosuppression for autoimmune hepatitis 2, 1

Stage 2: Small Varices (F1) Without High-Risk Features

• NSBBs (propranolol, nadolol) or carvedilol could be considered but evidence is conflicting—one meta-analysis suggests NSBBs are not effective in preventing progression from small to large varices 2
• Carvedilol showed superiority in one study (20.6% vs 38.6% progression to large varices, P=0.04) and may be preferred if treatment is initiated 2

Stage 3: Small Varices (F1) With High-Risk Features

• Initiate NSBBs immediately if small varices have red color signs on endoscopy or patient has decompensated cirrhosis (Child-Pugh B/C), as bleeding risk is significantly increased 2, 3
• Propranolol: Start 40 mg twice daily, titrate to 80 mg twice daily (or maximum tolerated dose) targeting 25% heart rate reduction or to 55 bpm 4
• Nadolol: Alternative NSBB with similar efficacy 4

Stage 4: Large Varices (F2/F3) - Primary Prophylaxis

• Carvedilol 12.5 mg/day is first-line therapy, achieving hemodynamic response in 50-75% of patients versus 46% with traditional NSBBs due to additional alpha-1 blockade that reduces intrahepatic resistance 1, 3, 5
• Traditional NSBBs (propranolol 40-80 mg twice daily or nadolol) remain acceptable alternatives when carvedilol is unavailable or not tolerated 1, 3
• Endoscopic variceal ligation (EVL) is an alternative for patients with contraindications to NSBBs, though NSBBs are preferred as they reduce portal pressure and prevent other complications 4

Acute Variceal Bleeding Management

Immediate Pharmacological Intervention

• Initiate vasoactive drugs immediately when variceal hemorrhage is suspected, before endoscopy: 1, 4, 3

  • Octreotide (somatostatin analog): Reduces splanchnic blood flow 4
  • Terlipressin 1 mg IV every 6 hours (equivalent to 0.85 mg terlipressin base): Superior to octreotide with longer half-life, increases MAP by 16.2 mmHg within 5 minutes, FDA-approved for hepatorenal syndrome type 1 4, 6
  • Somatostatin: Alternative vasoactive agent 1

• Temporarily suspend NSBBs if systolic BP <90 mmHg or mean arterial pressure <65 mmHg during acute bleeding 1, 3

Adjunctive Therapy

• Administer prophylactic antibiotics (maximum 7 days) immediately—intravenous ceftriaxone 1 g/24h is first choice—to reduce mortality, bacterial infections, and rebleeding 1, 3
• Transfuse red blood cells conservatively: Start when hemoglobin reaches 7 g/dL with goal of 7-9 g/dL, as excessive transfusion paradoxically increases portal pressure and worsens bleeding 3
• Continue vasoactive drugs for 2-5 days post-endoscopy, then transition to oral NSBBs 3
• Perform endoscopy within 12 hours once hemodynamically stable, with EVL if varices confirmed 1, 3

Secondary Prophylaxis (Prevention of Rebleeding)

• Combination therapy with NSBBs plus EVL is mandatory, significantly decreasing rebleeding compared to monotherapy (77% vs 58% 5-day hemostasis with combination vs endoscopy alone) 4, 3

Advanced Therapies

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

• TIPS is strongly recommended for gastroesophageal variceal bleeding refractory to endoscopic and medical therapy 1, 4
• Early/preemptive TIPS within 72 hours should be considered in high-risk patients: Child-Pugh C or MELD ≥19 1, 4, 3
• TIPS is recommended for refractory or recurrent ascites 1, 4
• Contraindications include bilirubin >50 μmol/L, platelets <75×10⁹, pre-existing encephalopathy, active infection, severe cardiac failure, and severe pulmonary hypertension 4

Adjunctive Medications in Decompensated Cirrhosis

• Simvastatin 20-40 mg/day (Child-Pugh A/B) or 10-20 mg/day (Child-Pugh C) improves endothelial dysfunction, enhances nitric oxide production, and decreases HVPG 7, 5
• Pentoxifylline may reduce liver-related complications by preventing bacterial translocation and systemic inflammation 2

Portal Hypertensive Gastropathy

• NSBBs (propranolol 40-80 mg twice daily) are recommended for chronic bleeding from portal hypertensive gastropathy to reduce iron-deficiency anemia 4, 3
• Add iron supplementation (oral or IV if severe anemia) to address chronic blood loss 4
• For refractory cases, consider endoscopic argon plasma coagulation or TIPS 4

Critical Safety Considerations and Contraindications

Absolute Contraindications for NSBBs

• Severe bradycardia, heart block, severe asthma, and decompensated heart failure 1

Situations Requiring NSBB Suspension or Extreme Caution

• Temporarily suspend during acute bleeding with systolic BP <90 mmHg or MAP <65 mmHg 1, 3
• Use extreme caution or suspend in refractory ascites with hypotension, as controversy exists regarding potential harm in this population 3

Important Prohibitions

• Do NOT routinely correct coagulation abnormalities before prophylactic band ligation in stable cirrhotic patients—provides no benefit and is not recommended 1, 3
• Do NOT use tranexamic acid in active variceal bleeding—this is contraindicated 1, 3
• Avoid large volumes of blood products as they may paradoxically increase portal pressure and worsen bleeding 3

Monitoring Parameters

• Target hemodynamic response: HVPG reduction to ≤12 mmHg or ≥20% reduction from baseline protects against acute variceal bleeding 4, 3
• Endoscopic surveillance every 2-3 years in compensated cirrhosis, every 1-2 years in decompensated cirrhosis 2
• Monitor heart rate (target 25% reduction or to 55 bpm), blood pressure, and liver function during NSBB therapy 4

Definitive Treatment

• Liver transplantation should be considered in all patients with decompensated cirrhosis, as it is the most effective approach to reduce portal pressure and improve survival 1, 3