Apixaban to Prevent Decompensation of Early Liver Cirrhosis Trial (APEACH)

Inclusion Criteria:

1. 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)
2. 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
3. Childs A Cirrhosis (Participants with a previous episode of decompensated cirrhosis who have now recompensated can be included)
4. Participants with no hepatic encephalopathy or low-grade hepatic encephalopathy (Grade 0 or 1) taking lactulose and/or rifaximin
5. Aged ≥18 years

6. 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:

1. 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)
2. Causes for cirrhosis other than alcohol, including those with MASLD who have never drunk alcohol above government recommended levels (14 units/week)
3. Pre-existing splanchnic vein thrombosis (portal, splenic, mesenteric, and hepatic veins)
4. Use of (and need for) anticoagulation or dual antiplatelet therapy or clopidogrel
5. Platelets <50x109/L at screening
6. Moderate-severe renal impairment defined as eGFR <30ml/min at screening
7. Recent variceal bleed or untreated large varices
8. Malignancy in last 2 years if unlikely to survive trial because of comorbidity in the location PI's opinion
9. Hepatocellular carcinoma
10. Severe cardiac failure1 or Chronic Obstructive Pulmonary Disease (COPD)
11. Pregnancy
12. INR >1.7 (After vitamin K correction) at screening
13. Previous hypersensitivity reaction to Apixaban