Non selective beta blockers (NSBBs), such as propranolol and nadolol, are mainstay therapies for portal hypertension in cirrhosis, but their efficacy and safety vary depending on the stage of the disease. Emerging evidence suggests that NSBBs may worsen the prognosis of advanced cirrhosis, especially in patients with a model for end-stage liver disease (MELD) score of >9. The purpose of this randomized controlled trial is to evaluate the effects of the use of propranolol as recommended by the guideline on the prognosis in cirrhotic patients with a MELD score of >9.

This is a non-inferiority, randomized controlled trial. A total of 466 decompensated cirrhotic patients with a MELD score of >9 will be enrolled. Participants will be stratified based on the presence or absence of acute decompensation at enrollment, and then randomly assigned at a 1:1 ratio to conventional treatment combined with or without propranolol groups. All patients will receive standard medical therapy in both groups, and then regularly followed. The primary outcome is further decompensation. The secondary outcomes include recompensation and death.

Inclusion Criteria:

• patients' age ≥18 years;
• patients with a definitive diagnosis of liver cirrhosis;
• patients with a MELD score of >9;
• patients with a history of decompensation or those who are experiencing their first decompensation, such as ascites, variceal bleeding, or hepatic encephalopathy (HE);
• patients' informed consents.

Exclusion Criteria:

• patients without a definite indication for NSBBs;
• patients with an absolute contraindication of NSBBs (severe bronchospasm, asthma, severe psychosis, high-degree atrioventricular block, etc.);
• patients with hypersensitivity to NSBBs;
• patients who had been treated with NSBBs before 2 weeks of enrollment;
• patients with occlusive portal vein thrombosis;
• patients who had undergone liver transplantation;
• patients who had undergone transjugular intrahepatic portosystemic shunt (TIPS);
• patients with a definitive diagnosis of hepatocellular carcinoma;
• patients with an estimated life time of <12 months due to the presence of any comorbidities;
• patients who are currently pregnant or breast-feeding.