Beta-blockers for Oesophageal Varices

Inclusion Criteria:

1. Age \>18 years
2. Cirrhosis and portal hypertension, defined by any 2 of the following:

   A) Characteristic clinical examination findings; one or more of i) liver function tests ii) haematological panel iii) coagulation profile abnormalities B) Characteristic radiological findings; one or more of i) heterogeneous, small liver with irregular contour ii) splenomegaly iii) ascites iv) varices v) recanalized umbilical vein C) Fibrosis score \> stage 4 on liver biopsy D) FibroScan liver stiffness measurement \>15 kilo Pascal without other explanation
3. Small oesophageal varices diagnosed within the last 3 months,- defined as \<5 mm in diameter or varices which completely disappear on moderate insufflation at gastroscopy.
4. Not received a beta-blocker in the last week
5. Capacity to provide informed consent

Exclusion Criteria:

1. Non-cirrhotic portal hypertension
2. Medium/large oesophageal varices (current or history of), defined as \>5 mm in diameter
3. Isolated gastric, duodenal, rectal varices with or without evidence of recent bleeding
4. Previous variceal haemorrhage
5. Red signs accompanying varices at endoscopy
6. Known intolerance to beta blockers
7. Contraindication to beta blocker use i) Heart rate \<50 bpm ii) Known 2nd degree or higher heart block iii) Sick sinus syndrome iv) Systolic blood pressure \<85 mm Hg v) Chronic airways obstruction (asthma/COPD) vi) Floppy Iris Syndrome vii) CYP2D6 Poor Metaboliser viii) History of cardiogenic shock ix) History of severe hypersensitivity reaction to beta-blockers x) Untreated phaeochromocytoma xi) Severe peripheral vascular disease xii) Prinzmetal angina xiii) New York Heart Association IV heart failure
8. Unable to provide informed consent
9. Child Pugh C cirrhosis
10. Already receiving a beta-blocker for another reason that cannot be discontinued
11. Graft cirrhosis post liver transplantation
12. Evidence of active malignancy without curative therapy planned
13. Pregnant or lactating women
14. Women of child bearing potential not willing to use adequate contraception during the protocol of IMP dosing
15. Patients who have been on a CTIMP within the previous 3 months