Portal Hypertension Pharmacotherapy

Portal hypertension pharmacotherapy lowers portal pressure and splanchnic flow to prevent and treat variceal bleeding, ascites and hepatorenal syndrome. It uses non-selective beta blockers, splanchnic vasoconstrictors, diuretics, albumin and antibiotics.

Mechanism. Non-selective beta blockers reduce cardiac output and splanchnic inflow. Vasopressin analogues and somatostatin analogues constrict splanchnic vessels. Spironolactone and furosemide reduce sodium and water retention.

• Propranolol 20 to 40 mg twice daily, titrated to a resting heart rate of 55 to 60 beats/min; maximum 160 mg daily without ascites and 80 mg daily with ascites.
• Nadolol 20 to 40 mg once daily; maximum 160 mg daily without ascites and 80 mg with ascites.
• Carvedilol 3.125 mg twice daily, increased after 3 days to 6.25 mg twice daily; maximum 12.5 mg daily.
• Terlipressin 2 mg intravenously every 4 hours for 48 hours, then 1 mg every 4 hours for up to 5 days.
• Octreotide 50 microgram intravenous bolus, then 50 microgram/h for 2 to 5 days.
• Spironolactone 100 mg with furosemide 40 mg daily for ascites, titrated every 3 to 5 days to a maximum of 400 mg and 160 mg daily.
• Albumin 20% for large-volume paracentesis (8 g for each litre removed over 5 litres) and for hepatorenal syndrome (20 to 40 g daily).

Differences. Carvedilol lowers portal pressure more than propranolol but lowers blood pressure more.

• Primary prevention of variceal bleeding: non-selective beta blocker for medium or large varices, or small varices with red signs or Child-Pugh C disease; band ligation if beta blockers are not tolerated.
• Acute variceal bleeding: start terlipressin or octreotide before endoscopy; endoscopy within 12 hours; band ligation; ceftriaxone 1 g intravenously daily for up to 7 days; transfuse to a haemoglobin of 7 to 8 g/dL.
• Secondary prevention: beta blocker plus band ligation.
• Ascites: spironolactone with furosemide; sodium restriction to 2 g daily.
• Spontaneous bacterial peritonitis: ceftriaxone 2 g daily for 5 to 7 days with albumin 1.5 g/kg on day 1 and 1 g/kg on day 3; prophylaxis with ciprofloxacin 500 mg daily or norfloxacin 400 mg daily after an episode.
• Hepatorenal syndrome with acute kidney injury: terlipressin with albumin.
• Regional: in hepatosplenic schistosomiasis, liver function is preserved and varices bleed; treat with a beta blocker and band ligation, and give praziquantel 40 mg/kg as a single dose for active infection. Hepatitis B is a common cause of cirrhosis and needs antiviral treatment.

Contraindications. Beta blockers: severe asthma or bronchospasm, second or third degree heart block, sick sinus syndrome, decompensated heart failure; stop with systolic pressure under 90 mmHg, serum sodium under 130 mmol/L, or acute kidney injury. Terlipressin: ischaemic heart or peripheral vascular disease, hypoxia, pregnancy.

Adverse effects. Beta blockers: bradycardia, hypotension, fatigue, bronchospasm. Terlipressin: abdominal pain, ischaemia, hyponatraemia, respiratory failure. Diuretics: hyperkalaemia, hyponatraemia, gynaecomastia, kidney injury.

Interactions. Spironolactone with ACE inhibitors raises potassium. NSAIDs precipitate kidney injury and diuretic resistance.

Special groups.

• Pregnancy: avoid terlipressin; beta blockers risk growth restriction and neonatal bradycardia.
• Breastfeeding: propranolol acceptable.
• Older adults: lower starting doses.
• Kidney impairment: nadolol accumulates; halve the dose when creatinine clearance is under 50 mL/min.
• Liver impairment: propranolol bioavailability rises; start low.

Monitoring. Heart rate, blood pressure, sodium, potassium, creatinine and daily weight.

Referral and escalation. All variceal bleeding, refractory ascites, hepatorenal syndrome and encephalopathy need admission and hepatology review; consider transjugular portosystemic shunt and transplant.