Primary prevention

Early detection of varices

The UK National Institute for Health and Care Excellence (NICE) recommends the following for patients with cirrhosis:[17]

Prevention of variceal bleeding

Follow local protocols for the primary prevention of variceal bleeding.

For patients with cirrhosis and medium to large oesophageal varices, NICE guidance recommends:[17]

  • Initiate a non-selective beta-blocker, specifically, carvedilol or propranolol.

    • Carvedilol and propranolol should be used with caution in people with cirrhosis because they have a greater effect on the heart rate and blood pressure of people with liver disease than those without.

    • Carvedilol should be avoided in people with severe hepatic impairment (for example, in those with large-volume or refractory ascites).

    • When starting treatment, use a low dose and titrate depending on the results of heart and blood pressure monitoring.

  • If non-selective beta-blockers are not tolerated, contraindicated, or the person cannot take tablets regularly because of their circumstances, offer endoscopic variceal band ligation (EVBL) instead.

    • The NICE guideline committee agreed it was important to discuss all treatment options, and talk about individual preferences and personal circumstances, to identify the right treatment.

    • NICE also advises that simultaneous EVBL can be considered if medium or large varices are detected during upper gastrointestinal endoscopy.

British Society of Gastroenterology (BSG) guidance aligns closely, but recommends propranolol as the first choice, with carvedilol or nadolol as valid alternatives.[5]

Baveno VII (the European consensus meeting on portal hypertension) also recommends propranolol, carvedilol, or nadolol as suitable first-line agents.[29] Carvedilol is preferred in compensated cirrhosis, since it is more effective at reducing hepatic venous pressure gradient. This is partly due to its intrinsic anti-alpha adrenergic vasodilatory effects.[29]

The role of combined treatment with non-selective beta blockers and EVBL is unclear.[17]

Band ligation of oesophageal varices for the primary prevention of bleeding reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared with no intervention.[30] Note that band ligation cannot be done successfully in patients with small varices; it is only used in patients with medium to large varices.[30]

Annual endoscopy should be offered to patients with cirrhosis and small oesophageal varices, in line with recommendations from the BSG.[5]

  • If there is clear evidence of disease progression, the BSG recommends modifying the endoscopy intervals according to clinical need.[5]

The role of non-selective beta-blockers for the primary prevention of bleeding in patients with cirrhosis and small varices is unclear.[5][17][31][32][33]​ A large, triple blinded, multi-centre randomised controlled trial looking at non-selective beta-blockers versus placebo for the primary prophylaxis of variceal haemorrhage in these patients is ongoing.[34]

Secondary prevention

Patients with acute variceal haemorrhage have a high risk of rebleeding (up to 60% at 1 year without prophylaxis) and therefore require treatment to prevent further episodes.[6]

  • The British Society of Gastroenterology (BSG) defines variceal rebleeding as the occurrence of a single episode of clinically significant rebleeding from portal hypertensive sources from day 5.[5]

    • Clinically significant rebleeding is defined as recurrent melaena or haematemesis alongside any of the following scenarios:[5] 

      • Hospital admission

      • Blood transfusion

      • 30 g/L drop in haemoglobin

      • Death within 6 weeks

The American Association for the Study of Liver Diseases (AASLD) recommends that secondary prophylaxis to prevent rebleeding should be instituted immediately after control of the index bleed, within 7 days from admission, because the highest risk period for rebleeding is the first 6 weeks after presentation.[6]

  • In patients who underwent pre-emptive transjugular intrahepatic portosystemic shunt (TIPS), no further measures are required.[6]

  • In patients who did not undergo TIPS, the recommended first-line approach for preventing variceal rebleeding is a combination of a non-selective beta-blocker and endoscopic variceal band ligation (EVBL).[5][6][29][75][76][77]

    • The Baveno VII consensus recommends propranolol, carvedilol, or nadolol as the preferred non-selective beta-blockers for this purpose.[29]

    • In patients undergoing EVBL, varices should be banded at 2- to 4-weekly intervals until eradication.[5] After successful elimination, endoscopy should be repeated at 3 months, and then every 6 months.[5] Recurrent varices should be treated with further EVBL until eradication.[5]

  • Non-selective beta-blockers or EVBL can be used as monotherapy as an alternative to combined treatment, taking into account the patient’s preferences and clinical judgement.[5]

    • If non-selective beta-blockers alone are used, further endoscopy is not necessary unless clinically indicated.[5] Non-invasive monitoring such as liver stiffness measurement can be used to guide therapy.[6]

    • EVBL alone is an option for patients who have contraindications to, or are unable to tolerate, a non-selective beta-blocker.[5]

  • TIPS is recommended for patients who experience rebleed despite combined non-selective beta-blockers plus EBVL, or with either intervention alone.[5][55]​ TIPS may also be considered based on patient preference where appropriate.[5]

    • TIPS using polytetrafluoroethylene (PTFE)-covered stents is recommended in preference to bare stents, as PTFE-covered stents are associated with a significantly higher primary patency rate, improved survival, and significantly lower rates of rebleeding.[78] 

    • Absolute contraindications to TIPS placement include:[6][55]​​[80] 

    • Relative contraindications to TIPS include:[6][80]

      • Severe obstructive arteriopathy

      • Hepatic artery and coeliac trunk stenosis (preventing adequate sinusoidal perfusion by the hepatic artery)

      • Recurrent hepatic encephalopathy

      • Hepatocellular carcinoma and other liver tumours

      • Bile duct dilation

      • Untreated biliary obstruction

      • Uncorrectable severe coagulopathy

    • In patients with Child-Pugh class A or B cirrhosis for whom TIPS is not feasible, shunt surgery may be considered, provided appropriate expertise and resources are available locally.[5] [ Cochrane Clinical Answers logo ]

  • For secondary prevention of variceal bleeding, BSG guidelines do not support the routine use of proton pump inhibitors, unless required for the treatment of peptic disease, nor the prophylactic use of clotting factors or platelet transfusions.[5]

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