Acute variceal bleeding in patients with cirrhosis and portal hypertension- APASL 2025

The management of **acute variceal bleeding (AVB)** in patients with cirrhosis and portal hypertension has been updated in the **Asia-Pacific Association for the Study of the Liver (APASL) 2025 guidelines**. These guidelines emphasize early diagnosis, rapid intervention, and standardized care to improve outcomes and reduce mortality. Below is a detailed summary of the key aspects of AVB management as per the APASL 2025 recommendations:

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### **Clinical Importance**

• **Acute variceal bleeding (AVB)** is a life-threatening complication of portal hypertension, with a **6-week mortality of 10–20%**.
• Timely intervention and adherence to updated protocols are critical for improving survival rates.

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### **Updated Definitions**

1. **AVB Definition**:

• Defined as **hematemesis** (vomiting blood) or **melena** (black tarry stools) within **24 hours** of presentation in suspected portal hypertension.
• This narrower definition helps distinguish AVB from re-bleeding episodes.

2. **Episode Duration**:

• An AVB episode is defined as lasting **48 hours** from the onset of the first bleed (**T0**).
• Any bleeding within this timeframe is considered part of the same episode.

3. **Re-Bleeding Categories**:

• **Very early re-bleeding**: 48–120 hours.
• **Early re-bleeding**: 6–42 days.
• **Late re-bleeding**: Beyond 42 days.

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### **Outcome Measures**

• Expanded outcome measures include:
• Survival rates.
• Duration of ICU and hospital stay.
• Development of new decompensations (e.g., ascites, jaundice, encephalopathy).
• **MELD score** changes.
• Quality of life assessments.

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### **Time Zero (T0) and Home-to-Door Time**

1. **T0 (Time Zero)**:

• Redefined as the **onset of the first bleed**, not hospital arrival.
• This allows better assessment of pre-hospital delays and early interventions.

2. **Home-to-Door Time**:

• Patients should reach the hospital ideally within **2 hours** (maximum **4 hours**) after the first bleed.
• Delays beyond **6 hours** significantly increase mortality.

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### **Diagnosis and Severity Assessment**

1. **Diagnosis**:

• Initial evaluation includes:
• **History**: Risk factors like alcohol use, hepatitis B/C, or metabolic-associated steatotic liver disease (MASLD).
• **Physical exam**: Signs like ascites, jaundice, and splenomegaly.
• **Laboratory tests**: Low platelets, high INR, elevated bilirubin.
• **Imaging**: Ultrasound or CT for portal hypertension.
• **Upper GI endoscopy** is the **gold standard** for diagnosis.

2. **Severity Assessment**:

• Predictors of severe bleeding include:
• High **hepatic venous pressure gradient (HVPG)**.
• Alcoholic liver disease.
• Infection.
• High **Child-Turcotte-Pugh (CTP)** or **MELD** score.
• Portal vein thrombosis.
• Active bleeding on endoscopy.
• The **APASL Bleed Severity Score** (0–7) is recommended for stratifying risk.

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### **Pre-Hospital and Emergency Management**

1. **Initial Resuscitation**:

• Prioritize **airway**, **breathing**, and **circulation** (ABC).
• Use **conservative fluid resuscitation** to avoid overcorrection.
• Target hemoglobin levels of **7–8 g/dL** with cautious transfusions.

2. **Pharmacotherapy**:

• Start **vasoactive agents** (terlipressin, somatostatin, or octreotide) within **30 minutes** of the first bleed.
• **Terlipressin infusion** is preferred.
• Administer prophylactic **antibiotics** (e.g., ceftriaxone) for **2–5 days** to prevent infections.

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### **Endoscopic Therapy**

1. **Timing**:

• Endoscopy should be performed within **12 hours** of stabilization, preferably within **6 hours**.
• Delayed endoscopy worsens outcomes.
• Bedside endoscopy in the ICU is acceptable for unstable patients.

2. **Therapeutic Options**:

• **Esophageal varices**: Endoscopic variceal ligation (**EVL**) is the first-line therapy.
• **Gastric varices**: Cyanoacrylate glue injection is preferred.
• Combination therapy (endoscopic + vasoactive drugs) is superior to either alone.

3. **Sedation and Prokinetics**:

• **Propofol** or **midazolam** sedation is safe, but minimal intubation is advised.
• Prokinetics (e.g., erythromycin, metoclopramide) improve mucosal visualization and reduce repeat procedures.

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### **Rescue Therapies**

• If bleeding persists despite combined medical and endoscopic treatment:

1. **Balloon tamponade** or **self-expanding metal stents** can provide temporary hemostasis.

2. **Transjugular intrahepatic portosystemic shunt (TIPS)**:

• Recommended within **72 hours** (ideally <24 hours) for high-risk patients.
• Improves survival in cases of uncontrolled bleeding.

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### **Radiology and Surgery**

1. **Interventional Radiology**:

• Plays a critical role in managing **complex gastric varices** or **refractory bleeding**.

2. **Surgical Options**:

• Surgical shunts are rarely used but may be considered as a **last-resort option**.

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### **Special Populations**

1. **Children**:

• AVB management in children requires tailored approaches based on age and etiology.

2. **MASLD-Related Cirrhosis**:

• AVB in metabolic-associated steatotic liver disease may require additional considerations.

3. **Patients on Anticoagulants**:

• Risk–benefit assessment is crucial for balancing bleeding risk with thrombotic risk.

4. **Hepatocellular Carcinoma (HCC)**:

• AVB in HCC patients requires individualized management.

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### **Research and Future Directions**

• **Artificial Intelligence (AI)**: Development of predictive models for AVB risk stratification.
• **Novel Hemostatic Devices**: Research on innovative tools for bleeding control.
• **Biomarkers**: Identification of better biomarkers for early diagnosis and prognosis.
• **Early TIPS Trials**: Further studies on the timing and indications for early TIPS.
• **Region-Specific Data**: Emphasis on generating data specific to Asia-Pacific populations.

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### **Conclusion**

The APASL 2025 guidelines provide a comprehensive framework for the management of acute variceal bleeding in patients with cirrhosis and portal hypertension. Early diagnosis, rapid initiation of therapy, and standardized care, along with the use of advanced interventions like TIPS and interventional radiology, are key to improving patient outcomes. Tailored approaches for special populations and ongoing research into novel therapies are also prioritized.