Apixaban to Prevent Decompensation of Early Liver Cirrhosis Trial

Inclusion criteria

• Liver cirrhosis secondary to alcohol, with or without associated metabolic risk factors, i.e. Alcohol related liver disease (ARLD) or metabolic dysfunction-associated steatotic liver disease, where there has been a significant history of alcohol consumption (MetALD)
• Cirrhosis will be based on histology, or clear radiological evidence, e.g. nodular or heterogeneous liver or non-invasive testing (e.g. Fibroscan®, or Enhanced Liver Fibrosis (ELF) test
• Childs A Cirrhosis (Participants with a previous episode of decompensated cirrhosis who have now recompensated can be included)
• Participants with no hepatic encephalopathy or low-grade hepatic encephalopathy (Grade 0 or 1) taking lactulose and/or rifaximin
• Aged ≥18 years
• Clinical evidence of portal hypertension, defined as any 1 of:

• Evidence of abdominal collateral circulation, recanalised umbilical vein or varices on imaging
• Asymptomatic ascites (trace only) seen around the liver on imaging in patients who are not taking diuretics
• Liver stiffness measurement >20kPa on FibroScan®/ Vibration- Controlled Transient Elastography (VCTE) (where BMI <35)
• Presence of Gastro-oesophageal varices at endoscopy
• Hepatic venous pressure gradient ≥ 10mmHg

Or Platelet count < 150,000 μL AND any 1 of:

• Spleen size >13 cm in length
• Liver stiffness measurement >20kPa on FibroScan®/VCTE (where BMI >35)
• Presence of portal hypertensive gastropathy at endoscopy

Exclusion criteria

• Evidence of decompensation (e.g. ascites requiring treatment other than a thin rim around liver on imaging, as above) (Evidence of decompensation as follows: Grade 2 or 3 Ascites, Grade 2 - 4 Hepatic Encephalopathy, Variceal Haemorrhage)
• Causes for cirrhosis other than alcohol, including those with MASLD who have never drunk alcohol above government recommended levels (14 units/week)
• Pre-existing splanchnic vein thrombosis (portal, splenic, mesenteric, and hepatic veins)
• Use of (and need for) anticoagulation or dual antiplatelet therapy or clopidogrel
• Platelets <50x109/L at screening
• Moderate-severe renal impairment defined as eGFR <30ml/min at screening
• Recent variceal bleed or untreated large varices
• Malignancy in last 2 years if unlikely to survive trial because of comorbidity in the location PI's opinion
• Hepatocellular carcinoma
• Severe cardiac failure1 or Chronic Obstructive Pulmonary Disease (COPD)
• Pregnancy
• INR >1.7 (After vitamin K correction) at screening
• Previous hypersensitivity reaction to Apixaban