Esophageal varices

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

decompensated cirrhosis with acute variceal hemorrhage (hepatic venous pressure gradient ≥10 mmHg)

1st line – supportive therapy + vasoactive drug + endoscopic therapy

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1st line –

supportive therapy + vasoactive drug + endoscopic therapy

Acute esophageal hemorrhage is a medical emergency. The immediate goal of treatment is to stop the bleeding, and to prevent early recurrence.

Initial measures should focus on resuscitation, assessment of the airway, and obtaining venous access.

Packed red blood cell transfusion should be undertaken using a restrictive strategy, targeting a hemoglobin level of 7 g/dL in patients without comorbidities.[5][37][38][45] Blood transfusion above this threshold may increase mortality.[46] In the context of resuscitation of an actively bleeding patient with hypotension, transfusion at higher hemoglobin levels may be appropriate due to the equilibration that occurs with fluid resuscitation.[47] Patients with comorbidities such as ischemic heart disease may also merit higher hemoglobin transfusion targets.[5][45] Platelets and coagulation factors should be given in certain circumstances. Patients on antiplatelet treatment should not receive platelet transfusions.[48]

Prolonged prothrombin time/international normalized ratio (PT/INR) should be corrected with fresh frozen plasma and/or vitamin K (phytonadione) in all patients except for those on warfarin treatment.[48] Prothrombin complex concentrate can be considered in patients on warfarin with a life-threatening gastrointestinal bleed or those with a supratherapeutic INR substantially exceeding the therapeutic range. Prothrombin complex concentrate can also be considered for patients in whom massive blood transfusion is undesirable because of its effect on coagulopathy or dilution of blood components.[48] Patients on direct oral anticoagulants (DOACs) should not routinely be given prothrombin complex concentrate; those on dabigatran should not routinely receive idarucizumab, and those on rivaroxaban or apixaban should not routinely receive recombinant coagulation factor Xa (andexanet alfa). These recommendations are based on limited evidence of benefit. However, reversal of anticoagulation with these agents may be considered in hospitalized patients with a life-threatening gastrointestinal bleed who have taken a DOAC within the past 24 hours.[48]

Patients on aspirin for secondary prevention should continue with this; if aspirin is stopped, it should be restarted on the day hemostasis is confirmed endoscopically.[48]

Pharmacologic therapy with a vasoactive drug (e.g., a somatostatin analog such as octreotide, or a vasopressin analog such as terlipressin) should be initiated as soon as variceal hemorrhage is suspected.[5][37][44][51][52]

Endoscopy should be performed within 12 hours of admission once the patient is hemodynamically stable. If hemorrhage is confirmed, it should be treated with endoscopic variceal ligation (EVL).[5][44][54] EVL is more effective than sclerotherapy for the control of bleeding, but scleropathy can be used when EVL is not feasible.[44] The combination of a vasoactive drug and EVL is considered as first-line therapy.[5][44]

Primary options

octreotide: 50 micrograms intravenously initially, followed by 25-50 micrograms/hour intravenous infusion for 2-5 days

terlipressin: 2 mg intravenously every 4-6 hours for 24-48 hours, followed by 1 mg every 4-6 hours for 2-5 days

Plus – prophylactic antibiotic therapy

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Plus –

prophylactic antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Short-term (until stability for discharge or 5 days, whichever is shorter) prophylactic antibiotics should be given to all patients with cirrhosis and variceal hemorrhage to cover gram-negative organisms. Prophylactic antibiotics reduce the rate of bacterial infection, treatment failure, rebleeding, and mortality.[5][37][44]

Guidelines recommend intravenous ceftriaxone for patients with advanced cirrhosis, and in hospital settings with a high prevalence of fluoroquinolone-resistant bacterial infections; however, systemic antimicrobial choice should be tailored to local hospital antimicrobial resistance and stewardship policies.[5][49] An oral fluoroquinolone (e.g., ciprofloxacin) may be used in the remaining patients.[44]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[50] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics that are commonly recommended for the infection are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Primary options

ceftriaxone: 1 g intravenously once daily

Secondary options

ciprofloxacin: 500 mg orally twice daily, or 400 mg intravenously every 12 hours

Consider – early transjugular intrahepatic porto-systemic shunt (TIPS)

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Consider –

early transjugular intrahepatic porto-systemic shunt (TIPS)

Treatment recommended for SOME patients in selected patient group

Early TIPS, within 72 hours (ideally <24 hours) from EGD/EVL, should be considered in high-risk patients, such as those with Child-Pugh class C (with a score <14) or class B with active bleeding at initial endoscopy despite concomitant treatment with vasoactive agent.[5][44][56] Patients may need transfer to a specialized center.[56]

Consider – nonselective beta-blocker

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Consider –

nonselective beta-blocker

Treatment recommended for SOME patients in selected patient group

For patients in whom an early transjugular intrahepatic porto-systemic shunt is not performed, the vasoactive drug should be continued for 2‐5 days and a nonselective beta-blocker initiated once the vasoactive drug is discontinued.[5]

Carvedilol (a nonselective beta-blocker with intrinsic alpha-adrenergic blocking activity) is the preferred drug for management of portal hypertension. Nadolol and propranolol are other options.[5]

Contraindications to each specific treatment, treatment tolerance, and compliance need to be considered.[4][5][44]

Monitor heart rate and blood pressure at each clinic visit; no need for follow-up endoscopy.

Primary options

carvedilol: 6.25 mg orally (immediate-release) once daily initially, increase to 6.25 mg twice daily after 3 days, maximum 12.5 mg/day

Secondary options

nadolol: 20-40 mg orally once daily initially, increase every 2-3 days according to response until treatment goals achieved, maximum 160 mg/day (without ascites) or 80 mg/day (with ascites)

propranolol hydrochloride: 20-40 mg orally (immediate-release) twice daily initially, increase every 2-3 days according to response until treatment goals achieved, maximum 320 mg/day (without ascites) or 160 mg/day (with ascites)

Consider – balloon tamponade or self-expanding metal mesh stent

decompensated cirrhosis with acute variceal hemorrhage and failed endoscopic/pharmacologic therapy

1st line – rescue transjugular intrahepatic porto-systemic shunt (TIPS)

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1st line –

rescue transjugular intrahepatic porto-systemic shunt (TIPS)

When the combination of a vasoactive drug and endoscopic variceal ligation fails to stop the bleeding, TIPS is indicated as a rescue therapy.[5][44][56] Patients may need urgent transfer to a specialized center.[56]

It should be noted that TIPS is not recommended in patients with a Model of End-stage Liver Disease (MELD) score >30, lactate >12 mmol/L, or Child-Pugh >13, unless it is a bridge to liver transplantation in the short term, due to the high risk of mortality post-TIPS in these patients.[56]

Consider – balloon tamponade or self-expanding metal mesh stent

ONGOING

compensated cirrhosis with mild portal hypertension (hepatic venous pressure gradient >5 and <10 mmHg)

1st line – treat underlying cause plus monitoring

Back

1st line –

treat underlying cause plus monitoring

Defined as hepatic venous pressure gradient >5 but <10 mmHg.[5][58] Patients do not have varices.

The goal of therapy is to eliminate the etiologic factor (e.g., hepatitis B, hepatitis C, alcohol, and iron), make lifestyle modifications, and prevent clinically significant portal hypertension. Regression of cirrhosis may be possible in some patients.[5]

Nonselective beta-blockers are not recommended in these patients because they do not reduce the incidence of new varices, variceal bleeding, or clinical decompensation at this stage.[5]

Patients with compensated cirrhosis should undergo regular (6-monthly) ultrasound imaging to screen for hepatocellular carcinoma and portal vein thrombosis; special attention should be paid to imaging evidence indicating the development of clinically significant portal hypertension.[5]

Annual liver stiffness measurement can identify patients who would benefit from endoscopic screening.[5]

compensated cirrhosis with clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mmHg): without gastroesophageal varices

1st line – nonselective beta-blocker

Back

1st line –

nonselective beta-blocker

The principal goal of treatment for patients with compensated cirrhosis with clinically significant portal hypertension is to prevent clinical decompensation, followed by the prevention of gastroesophageal varices.[5]

Nonselective beta-blockers should be considered to prevent decompensation.[5] Carvedilol (a nonselective beta-blocker with intrinsic alpha-adrenergic blocking activity) is the preferred drug for management of portal hypertension. Nadolol and propranolol are other options.[5]

Contraindications to each specific treatment, treatment tolerance, and compliance need to be considered.[4][5][44]

Monitor heart rate and blood pressure at each clinic visit; no need for follow-up endoscopy.

Primary options

carvedilol: 6.25 mg orally (immediate-release) once daily initially, increase to 6.25 mg twice daily after 3 days, maximum 12.5 mg/day

Secondary options

nadolol: 20-40 mg orally once daily initially, increase every 2-3 days according to response until treatment goals achieved, maximum 160 mg/day (without ascites) or 80 mg/day (with ascites)

2nd line – endoscopic surveillance

compensated cirrhosis with clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mmHg): with gastroesophageal varices (no bleeding)

small varices

1st line – nonselective beta-blocker

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1st line –

nonselective beta-blocker

Nonselective beta-blockers are recommended for prevention of first variceal hemorrhage in all patients with small gastroesophageal varices who do not have a contraindication or intolerance to beta-blockers.[5]

Carvedilol (a nonselective beta-blocker with intrinsic alpha-adrenergic blocking activity) is the preferred drug for management of portal hypertension. Nadolol and propranolol are other options.[5]

Contraindications to each specific treatment, treatment tolerance, and compliance need to be considered.[4][5][44]

Monitor heart rate and blood pressure at each clinic visit; no need for follow-up endoscopy.

Primary options

carvedilol: 6.25 mg orally (immediate-release) once daily initially, increase to 6.25 mg twice daily after 3 days, maximum 12.5 mg/day

Secondary options

nadolol: 20-40 mg orally once daily initially, increase every 2-3 days according to response until treatment goals achieved, maximum 160 mg/day (without ascites) or 80 mg/day (with ascites)

2nd line – endoscopic surveillance

medium to large varices

1st line – nonselective beta-blocker

Back

1st line –

nonselective beta-blocker

Nonselective beta-blockers are recommended to prevent the first variceal hemorrhage in all patients with medium to large varices who do not have a contraindication or intolerance to beta-blockers.[5]

Carvedilol (a nonselective beta-blocker with intrinsic alpha-adrenergic blocking activity) is the preferred drug for management of portal hypertension. Nadolol and propranolol are other options.[5]

Contraindications to each specific treatment, treatment tolerance, and compliance need to be considered.[4][5][44]

Monitor heart rate and blood pressure at each clinic visit; no need for follow-up endoscopy.

Primary options

carvedilol: 6.25 mg orally (immediate-release) once daily initially, increase to 6.25 mg twice daily after 3 days, maximum 12.5 mg/day

Secondary options

nadolol: 20-40 mg orally once daily initially, increase every 2-3 days according to response until treatment goals achieved, maximum 160 mg/day (without ascites) or 80 mg/day (with ascites)

1st line – endoscopic variceal ligation (EVL)

2nd line – endoscopic surveillance

previous variceal bleed

1st line – nonselective beta-blocker plus endoscopic variceal ligation (EVL)

Back

1st line –

nonselective beta-blocker plus endoscopic variceal ligation (EVL)

The first-line treatment for prevention of rebleeding is a combination of a nonselective beta-blocker plus EVL.[5][38][44][60][61]

Contraindications to each specific treatment, treatment tolerance, and compliance need to be considered.[4][5][44]

Carvedilol (a nonselective beta-blocker with intrinsic alpha-adrenergic blocking activity) is the preferred drug for management of portal hypertension. Nadolol and propranolol are other options.[5]

Monitor heart rate and blood pressure at each clinic visit; no need for follow-up endoscopy.

Patients who have undergone successful transjugular intrahepatic porto-systemic shunt (TIPS) during the acute bleeding episode do not require nonselective beta-blockers or EVL. Patency of TIPS should be assessed by doppler ultrasound at 1 week, 3 months, 6 months, and every 6 months thereafter.[56]

Primary options

carvedilol: 6.25 mg orally (immediate-release) once daily initially, increase to 6.25 mg twice daily after 3 days, maximum 12.5 mg/day

Secondary options

nadolol: 20-40 mg orally once daily initially, increase every 2-3 days according to response until treatment goals achieved, maximum 160 mg/day (without ascites) or 80 mg/day (with ascites)

2nd line – transjugular intrahepatic porto-systemic shunt (TIPS)

Back

2nd line –

transjugular intrahepatic porto-systemic shunt (TIPS)

TIPS is recommended for patients who rebleed despite combined endoscopic variceal ligation and nonselective beta-blocker therapy (or when combination therapy is not tolerated or is contraindicated).[5][44][56]

However, TIPS did not increase survival time or quality of life compared with hepatic venous pressure gradient-based medical therapy, and resulted in slightly more adverse events.[64] Moreover, reduction in rebleeding is attenuated if TIPS is placed more than 3 weeks after the index bleed.

TIPS with polytetrafluoroethylene (PTFE)-covered stents should be used in preference to bare stents.[56] There is evidence that they are associated with a significantly higher primary patency rate and survival rate and a significantly decreased rebleeding rate.[62]

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Esophageal varices

Treatment algorithm

decompensated cirrhosis with acute variceal hemorrhage (hepatic venous pressure gradient ≥10 mmHg)

supportive therapy + vasoactive drug + endoscopic therapy

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

prophylactic antibiotic therapy

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

early transjugular intrahepatic porto-systemic shunt (TIPS)

nonselective beta-blocker

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

balloon tamponade or self-expanding metal mesh stent

decompensated cirrhosis with acute variceal hemorrhage and failed endoscopic/pharmacologic therapy

rescue transjugular intrahepatic porto-systemic shunt (TIPS)

balloon tamponade or self-expanding metal mesh stent

compensated cirrhosis with mild portal hypertension (hepatic venous pressure gradient >5 and <10 mmHg)

treat underlying cause plus monitoring

compensated cirrhosis with clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mmHg): without gastroesophageal varices

nonselective beta-blocker

Primary options

Secondary options

endoscopic surveillance

compensated cirrhosis with clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mmHg): with gastroesophageal varices (no bleeding)

small varices

nonselective beta-blocker

Primary options

Secondary options

endoscopic surveillance

medium to large varices

nonselective beta-blocker

Primary options

Secondary options

endoscopic variceal ligation (EVL)

endoscopic surveillance

previous variceal bleed

nonselective beta-blocker plus endoscopic variceal ligation (EVL)

Primary options

Secondary options

transjugular intrahepatic porto-systemic shunt (TIPS)