What is the management plan for chronic liver disease with portal hypertension?

Management of Chronic Liver Disease with Portal Hypertension

The cornerstone of portal hypertension management is non-selective beta-blockers (NSBBs) for variceal prophylaxis, combined with endoscopic therapy when indicated, while TIPS serves as rescue therapy for refractory complications. 1, 2

Risk Stratification and Initial Assessment

The first step is determining the stage of portal hypertension through hepatic venous pressure gradient (HVPG) measurement when available:

• Clinically significant portal hypertension (CSPH) is defined as HVPG ≥10 mmHg, which marks the threshold for developing varices and clinical decompensation 1
• HVPG ≥12 mmHg predicts risk of variceal bleeding and ascites 1
• HVPG ≥16 mmHg independently predicts higher mortality in both compensated and decompensated cirrhosis 1
• When HVPG is unavailable, liver stiffness measurement combined with platelet count can non-invasively identify CSPH 3

All patients with confirmed portal hypertension require upper endoscopy to screen for gastroesophageal varices. 4

Primary Prophylaxis (Preventing First Variceal Bleed)

For Patients WITH Varices:

NSBBs are the preferred first-line therapy over endoscopic band ligation (EBL) because they reduce portal pressure systemically and prevent other complications beyond variceal bleeding. 1, 2

Carvedilol is now the NSBB of choice, superior to traditional propranolol or nadolol: 5

• Target dose: 12.5 mg/day 5
• More effective at reducing portal pressure than propranolol or nadolol 3, 5
• Reduces risk of hepatic decompensation in patients with CSPH 3, 5
• Acts on both hyperdynamic circulation/splanchnic vasodilation AND intrahepatic resistance 5

Hemodynamic goals: Reduce HVPG to ≤12 mmHg or achieve ≥20% reduction from baseline 1, 2

Important caveat: NSBBs are mostly ineffective in compensated cirrhosis with mild portal hypertension (HVPG <10 mmHg) because the hyperdynamic circulatory state is not yet fully developed 1

For Patients WITHOUT Varices but WITH CSPH:

• Do NOT use NSBBs solely to prevent variceal formation - a large randomized trial with timolol showed no benefit 1
• The treatment goal at this stage should be preventing clinical decompensation, not just preventing varices 1
• Ongoing trials are evaluating NSBBs for preventing decompensation in this population 1

Acute Variceal Bleeding Management

Immediate vasoactive drug therapy BEFORE endoscopy is mandatory: 1, 2

1. Start vasoactive agents immediately upon presentation: 1, 2

   • Octreotide (somatostatin analog) reduces splanchnic blood flow 2
   • Terlipressin (synthetic vasopressin analog) is more effective than octreotide with longer half-life and fewer adverse effects 2
   • Combination of vasoactive drugs plus endoscopy achieves 77% 5-day hemostasis vs 58% with endoscopy alone 1, 2

2. Add prophylactic antibiotics immediately - reduces mortality, bacterial infections, and rebleeding 1, 2

3. Perform endoscopic therapy once patient is stabilized (after vasoactive drugs initiated and bleeding slowed) 1

Secondary Prophylaxis (Preventing Rebleeding)

Combination therapy with NSBBs PLUS endoscopic band ligation is superior to either alone: 2, 4

• Carvedilol plus EBL may prevent both rebleeding AND non-bleeding decompensation better than propranolol plus EBL 5
• This combined approach significantly decreases rebleeding compared to monotherapy 2

TIPS: Rescue Therapy for Refractory Cases

TIPS is strongly indicated for: 1, 2, 4

• Variceal bleeding refractory to endoscopic and drug therapy 1, 2
• Refractory or recurrent ascites 1, 2, 4
• Selected cases of hepatic hydrothorax 1, 2

Early/pre-emptive TIPS within 72 hours should be considered in high-risk patients: 1, 2

• Child-Pugh class C disease 1, 2
• MELD score ≥19 1, 2

TIPS hemodynamic target: Reduce portal pressure gradient to <12 mmHg or ≥20% reduction from baseline for variceal bleeding 1

Absolute contraindications to TIPS: 1, 4

• Severe left ventricular dysfunction or severe pulmonary hypertension 1, 4
• Bilirubin >50 μmol/L 1
• Platelets <75×10⁹/L 1
• Active infection 1

Relative contraindications: 4

• Pre-existing hepatic encephalopathy 4
• Age >65 years (increased encephalopathy risk) 4

Cardiac evaluation before elective TIPS is mandatory: 4

• Perform cardiac history, examination, 12-lead ECG, and NT-proBNP in all patients 4
• If abnormal, obtain echocardiogram and cardiology consultation 4

Management of Other Portal Hypertension Complications

Portal Hypertensive Gastropathy:

For chronic bleeding causing anemia: 1

• NSBBs are recommended to lower portal pressure 1
• Iron supplementation 1
• Argon plasma coagulation for active bleeding 1
• TIPS for refractory cases 1

Critical distinction: Portal hypertensive gastropathy bleeding responds to portal pressure-lowering measures, NOT correction of coagulation abnormalities 1

Hepatic Encephalopathy:

Lactulose is first-line therapy: 6

• Dose: 30-45 mL (20-30 grams) three to four times daily orally 6
• Goal: Produce 2-3 soft stools daily 6
• For acute/severe encephalopathy: Hourly doses of 30-45 mL until laxative effect achieved 6
• Rectal administration (300 mL lactulose mixed with 700 mL water/saline, retained 30-60 minutes) for patients unable to take oral medication 6
• Reduces blood ammonia by 25-50% with clinical response in ~75% of patients 6

Post-TIPS encephalopathy management: 1, 2

• Affects approximately one-third of patients after TIPS 2
• Most cases respond to medical therapy 2
• Severe cases may require TIPS diameter reduction or occlusion 2

Ascites Management:

• Diuretics remain standard therapy 2
• Caution with NSBBs in patients with ascites: Propranolol has antinatriuretic effects that may limit diuretic efficacy 7
• Carvedilol appears safer in patients with ascites and varices, as long as arterial blood pressure is maintained 5
• TIPS for refractory ascites 1, 2, 4

Monitoring and Follow-up

Post-TIPS surveillance: 1

• Doppler ultrasound 1 week after TIPSS in patients with prothrombotic conditions 1
• Doppler ultrasound at 6-12 month intervals in other patients 1
• No routine venography needed except in prothrombotic conditions 1

NSBB therapy monitoring: 1

• Heart rate changes do NOT correlate with HVPG changes 1
• Routine HVPG monitoring is not recommended 1
• Monitor for signs of hepatic decompensation (ascites, encephalopathy, variceal bleeding) 8

Critical Safety Considerations

NSBBs must be avoided or used with extreme caution in: 5, 7

• Decompensated cirrhosis with refractory ascites (risk of hemodynamic impairment) 5
• Systemic hemodynamic impairment or renal dysfunction 5
• Patients with significant hypotension 5

Metformin considerations in diabetic patients with portal hypertension: 8

• Safe ONLY in compensated cirrhosis (Child-Pugh A) with eGFR ≥30 mL/min/1.73 m² 8
• Must be avoided in decompensated cirrhosis due to lactic acidosis risk 8
• Assess for signs of hepatic decompensation before continuing 8