Inclusion criteria |
Cirrhosis and portal hypertension, defined by any 2 of the following: |
- Characteristic clinical examination findings; one or more of |
- Characteristic liver function tests |
- Haematological panel |
- Coagulation profile abnormalities |
- Characteristic radiological findings; one or more of |
- Heterogeneous liver with irregular contour |
- Splenomegaly |
- Ascites |
- Varices |
- Recanalized umbilical vein |
- FibroScan liver stiffness measurement > 15 kPa without other explanation |
- Fibrosis score > ISHAK stage 4 on liver biopsy |
Small oesophageal varices diagnosed within the last 6 monthsa |
Not received a beta-blocker in the last week |
Capacity to provide informed consent |
Exclusion criteria |
Non-cirrhotic portal hypertension |
Current medium/large oesophageal varices (defined as > 5 mm in diameter) |
Previous medium/large oesophageal varices, which decreased in size with curative therapy |
Gastric (IGV and GOV2), duodenal, rectal or other ectopic varices with or without evidence of recent bleeding. For gastric varices, this includes the following: IGV-1 and IGV-2 (isolated gastric varices) and GOV2 (gastric varices continuing into the cardia) |
⦁ [GOV1 (gastric varices continuing into the lesser curve) are not an exclusion if present with small oesophageal varices] |
Previous variceal haemorrhage |
Previous band ligation or glue injection of oesophageal and/or gastric varices |
Red signs accompanying small oesophageal varices at endoscopy |
Known intolerance to beta blockers |
Contraindications to beta-blocker use: Heart rate < 50 bpm, known 2nd degree or higher heart block, sick sinus syndrome, systolic blood pressure < 85 mmHg, chronic airways obstruction (asthma/COPD), Floppy Iris Syndrome, CYP2D6 poor metaboliser, history of cardiogenic shock, history of severe hypersensitivity reaction to beta-blockers, untreated phaeochromocytoma, severe peripheral vascular disease, prinzmetal angina and NYHA IV heart failure |
Unable to provide informed consenta |
Child–Pugh C cirrhosisa |
Already receiving a beta-blocker for another reason that cannot be discontinued |
Graft cirrhosis post liver transplantation |
Evidence of active malignancy without curative therapy planned |
Pregnant or lactating womena |
Women of child bearing potential not willing to use adequate contraception during the period of IMP dosing (if relevant) |
Patients who have been on a CTIMP within the previous 3 months |
Clinical symptoms consistent with COVID-19 at the time of randomisation |