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

Prior treatment

• Current use of non-selective beta-blocker (NSBB) or any use of NSBB within 6 months before
  • 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 be kept unchanged in conventional arm if there is clinical need for the selective beta-blocker
• 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
• Current or history of decompensated liver cirrhosis (i.e. Child's C cirrhosis, prior decompensating events such as ascites, variceal bleeding, hepatic encephalopathy and hepatorenal syndrome)
  • o Child's B cirrhosis without decompensating events is not excluded
• Liver transplantation

Other illness

• Contraindication to NSBB (e.g. Type II/III heart block or baseline bradycardia \<60/minute, hypotension with systolic blood pressure (SBP) \<100 mmHg, asthma, poorly controlled chronic obstructive pulmonary disease, and peripheral vascular disease)
• Contraindication to OGD (e.g. Intestinal perforation or obstruction)
• Current or history of hepatocellular carcinoma (HCC)
• Current or history of portal vein thrombosis
• Serious medical illness with limited life expectancy of less than 6 months

Other

• Presence of high-risk varices (HRV) (i.e. moderate to large oesophageal varices \[OV\] or OV with red wale sign) found in OGD
• Transjugular intrahepatic portosystemic shunt (TIPS)
• Pregnancy
• Unable to obtain or refusal of informed consent from patient

• 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 and non-obese MASLD) or ANTICIPATE-NASH model (for obese MASLD) within 6 months from screening
  • 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)