What defines failure of endoscopic therapy for portal hypertension‑related varices?

Definition of Failure of Endoscopic Therapy for Portal Hypertension-Related Varices

Failure of endoscopic therapy for variceal bleeding is defined as continued or recurrent significant bleeding within the first 5 days (the "index bleed" period) after initial endoscopic intervention, despite combined pharmacologic and endoscopic treatment. 1

Specific Clinical Criteria

The most recent EASL guidelines (2025) provide precise criteria for defining failure to control bleeding, which occurs only within the index bleed (first 5 days): 1

• Fresh hematemesis occurring at least 2 hours after initiating vasoactive medication or completing therapeutic endoscopy 1
• Hypovolemic shock developing after initial treatment 1
• Hemoglobin drop of ≥3 g/dL (or ≥9% hematocrit reduction) at any time, provided no blood transfusion has been administered 1

Critical Distinction: Two Types of Endoscopic Failure

The 2025 EASL guidelines emphasize distinguishing between two clinically distinct scenarios: 1

• "Salvage TIPS" scenario: Endoscopic treatment is not technically possible or fails immediately—bleeding cannot be controlled from the outset 1
• "Rescue TIPS" scenario: Initial endoscopic control is achieved, but rebleeding occurs within the first 5 days despite that initial success 1

Both scenarios constitute endoscopic therapy failure and warrant the same management (covered TIPS), but they carry different prognoses and should be documented separately. 1

Timeframe Matters

The definition is time-sensitive and structured around specific bleeding windows: 1

• 0-5 days (index bleed): The period when "failure to control bleeding" is defined; highest bleeding-related risk 1
• 5 days-6 weeks: Rebleeding during this period is considered "early rebleeding" but is distinct from failure to control the index bleed 1
• Beyond 6 weeks: Late rebleeding, managed as secondary prophylaxis failure 1

Risk Factors Predicting Endoscopic Failure

Multiple guidelines identify patients at high risk of endoscopic therapy failure who may benefit from pre-emptive TIPS: 1

• Child-Pugh class B with active bleeding at endoscopy 1
• Child-Pugh class C with MELD score <14 1
• Hepatic venous pressure gradient (HVPG) >20 mmHg measured within 24 hours 1
• Child-Pugh score >8 1
• MELD score >19 1
• Presence of bacterial infections or acute-on-chronic liver failure (ACLF) 1

Management When Endoscopic Therapy Fails

When the above criteria for failure are met: 1

• Immediate bridge therapy: Balloon tamponade or esophageal self-expandable metal stents (maximum 24 hours) until definitive treatment 1
• Salvage/rescue covered TIPS: Should be performed urgently, controlling bleeding in >90% of cases 1
• Surgical shunts: Reserved only for patients where TIPS is not feasible due to anatomical/technical problems or lack of expertise 1

Common Pitfall to Avoid

Do not wait beyond 5 days to declare treatment failure. The definition specifically applies to the index bleed period, and delays in recognizing failure lead to increased mortality (approximately 40% within 42 days for uncontrolled bleeding). 1 The 6-week and 1-year mortality after rescue TIPS remains high at 33% and 46% respectively, emphasizing the importance of early recognition and intervention. 1

Special Consideration for Gastric Varices

For gastric varices, particularly GOV2 and IGV1, endoscopic therapy failure has different implications: 1

• Endoscopic cyanoacrylate injection (ECI) is the preferred endoscopic method, not band ligation 1
• TIPS combined with direct variceal embolization is often required for cardiofundal varices when endoscopic therapy fails, as TIPS alone may allow continued flow through the varices 1
• Balloon-occluded retrograde transvenous obliteration (BRTO) may be superior to TIPS alone for cardiofundal varices, with less rebleeding and encephalopathy 1