Non-selective Beta-blocker in Compensated Advanced Chronic Liver Disease

Inclusion Criteria:

• Aged 18 years of above

• Established diagnosis of chronic liver disease(s) of the following etiologies

• Alcohol-related liver disease (ARLD)

• Chronic hepatitis B (CHB)

• Chronic hepatitis C (CHC)

• Metabolic dysfunction-associated steatotic liver disease (MASLD) § Non-obese (BMI <30kg/m2) and obese (BMI ≥30 kg/m2)

• In high-risk grey zone or CSPH, by Baveno VII criteria (for ARLD, CHB, CHC andnon-obese MASLD) or ANTICIPATE-NASH model (for obese MASLD) within 6 months fromscreening

• Baveno VII criteria (for ARLD, CHB, CHC and non-obese MASLD)

• LSM ≥25 kPa (CSPH)

• LSM ≥20 kPa - <25 kPa and platelet count <150 x 10^9/L; or LSM ≥15 kPa - <20 kPa and platelet count <110 x 10^9/L (high-risk grey zone)

• ANTICIPATE-NASH model (for obese MASLD)

• Predictive probability for CSPH >90% (CSPH)

• Predictive probability for CSPH ≥60% - <90% (high-risk grey zone)

Exclusion Criteria:

• Presence of high-risk varices (HRV) (i.e. moderate to large oesophageal varices [OV]or OV with red wale sign) found in OGD

• Current use of non-selective beta-blocker (NSBB) or any use of NSBB within 6 monthsbefore

• Use of selective beta blocker, such as atenolol or metoprolol, is not excluded

• Selective beta-blocker will be switched to carvedilol in NSBB arm, and will bekept unchanged in conventional arm if there is clinical need for the selectivebeta-blocker

• Contraindication to NSBB (e.g. Type II/III heart block or baseline bradycardia <60/minute, hypotension with systolic blood pressure (SBP) <100 mmHg, asthma, poorlycontrolled chronic obstructive pulmonary disease, and peripheral vascular disease)

• Current use of nitrated drugs or any use of nitrated drugs within 6 months before o Use of sublingual nitrate, such as glyceryl trinitrate, is not excluded

• Contraindication to OGD (e.g. Intestinal perforation or obstruction)

• Current or history of decompensated liver cirrhosis (i.e. Child's C cirrhosis, priordecompensating events such as ascites, variceal bleeding, hepatic encephalopathy andhepatorenal syndrome) o Child's B cirrhosis without decompensating events is not excluded

• Current or history of hepatocellular carcinoma (HCC)

• Current or history of portal vein thrombosis

• Transjugular intrahepatic portosystemic shunt (TIPS)

• Liver transplantation

• Serious medical illness with limited life expectancy of less than 6 months

• Pregnancy

• Unable to obtain or refusal of informed consent from patient