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Esophageal Varices
Edward Feller, MD, FACP, FACG
image BASICS
DESCRIPTION
  • Dilated distal esophageal veins connecting the portal and systemic circulations
  • Results from portal hypertension (most commonly due to liver cirrhosis), resistance to portal blood flow, and increased portal venous blood inflow
  • Superficial location of distal esophageal veins makes them susceptible to rupture.
  • Esophageal variceal rupture: Most common fatal complication of cirrhosis; severity of liver disease correlates with presence of varices and risk of bleeding.
EPIDEMIOLOGY
Incidence
  • At diagnosis, 30% of cirrhotic patients have varices; increases to 90% at 10 years (1).
  • 1-year rate of first variceal bleeding is 5% for small varices, 15% for large varices.
Pediatric Considerations
Portal hypertension is common in chronic liver disease in children. No clear guidelines for screening; pharmacologic or endoscopic treatment are equivalent (2)[A].
Prevalence
  • 50% of patients with esophageal varices will experience bleeding at some point.
  • Variceal bleeding: 15-20% mortality in the following 6 weeks after the episode
  • Gender: male > female
ETIOLOGY AND PATHOPHYSIOLOGY
  • Fibrous tissue and regenerative nodules in cirrhosis lead to splanchnic arteriolar vasodilatation, increased portal inflow, and increased resistance to outflow resulting in portal hypertension. Increased production of endothelin-1 and decreased production of nitrous oxide causes intrahepatic vasoconstriction, with further reduction in flow (1).
  • Portal hypertension: pressure gradient >10 mm Hg between the portal vein and inferior vena cava. Collateral vessels (varices) form to decompress portal circulation.
  • Cirrhotic portal hypertension
    • >90% of cases due to alcohol and HCV
    • Less common: hemochromatosis, hepatitis B, nonalcoholic fatty liver disease, primary biliary cirrhosis and autoimmune cirrhosis
  • Noncirrhotic portal hypertension
    • Extrahepatic portal or splenic vein thrombosis, trauma, chronic pancreatitis, thrombotic disease, polycythemia
    • Metastasis to liver sinusoids/portal vein: lymphoma, leukemia, hepatoma, or other carcinomas
    • Metabolic disease altering liver sinusoids: amyloidosis, Gaucher disease, Budd-Chiari syndrome, veno-occlusive disease
Genetics
Cirrhosis is rarely hereditary.
RISK FACTORS
  • Cirrhosis due to any cause
  • In cirrhotic patients, thrombocytopenia and splenomegaly, correlated with portal hypertension, are independent predictors of esophageal varices.
  • Noncirrhotic portal hypertension
  • Increased bleeding risk in known varices include varix size and endoscopic signs (red wale marks, cherry-red spots); vessel wall thickness; abrupt increase in variceal pressure (i.e., Valsalva maneuver)
  • MELD/Child-Pugh score; presence of portal vein thrombosis; high hepatic venous pressure gradient [HVPG])
GENERAL PREVENTION
  • Prevent underlying causes: alcoholism, hepatitis B vaccine, needle hygiene, detox in IV drug use (IVDU) to avoid HCV exposure; specific screening and therapy for hepatitis B and C, hemochromatosis (1)
  • See “Treatment” for prevention of first and second bleeds.
COMMONLY ASSOCIATED CONDITIONS
  • Portal hypertensive gastropathy; varices in stomach, duodenum, colon, rectum (causes massive bleeding, unlike hemorrhoids); rarely at umbilicus (caput medusa) or ostomy sites
  • Isolated gastric varices can occur due to splenic vein thrombosis/stenosis from hypercoagulability/contiguous inflammation (most commonly, chronic pancreatitis). Tumors can compress/infiltrate the splenic vein leading to pressure increase in short gastric veins. Signs of portal hypertension or esophageal varices may be absent (3).
  • Other complications of cirrhosis: hepatic encephalopathy, ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma
image DIAGNOSIS
  • First indication of varices often associated with GI bleeding episode: painless hematemesis, hematochezia, and/or melena
  • Occult bleeding (anemia): uncommon
PHYSICAL EXAM
  • Assess hemodynamic stability: hypotension, tachycardia (active bleeding).
  • Assess airway integrity.
  • Abdominal exam—liver palpation/percussion (often small and firm with cirrhosis)
  • Splenomegaly, ascites (shifting dullness; puddle splash)
  • Visible abdominal periumbilical collateral circulation (caput medusae)
  • Peripheral stigmata of alcoholism: spider angiomata on chest/back, palmar erythema, testicular atrophy, gynecomastia
  • Anal varices (which collapse with digital pressure, whereas hemorrhoids do not)
  • Hepatic encephalopathy; asterixis
  • Blood on rectal exam
DIFFERENTIAL DIAGNOSIS
  • Upper GI bleeding: 10-30% are due to varices.
    • In patients with known varices, as many as 50% bleed from nonvariceal sources.
    • Peptic ulcer; gastritis
    • Gastric/esophageal malignancy
    • Congestive gastropathy of portal hypertension
    • Arteriovenous malformation
    • Mallory-Weiss tears
    • Aortoenteric fistula
    • Hemoptysis; nosebleed
  • Lower GI bleeding
    • Rectal varices; hemorrhoids
    • Colonic neoplasia
    • Diverticulosis/arteriovenous malformation
    • Rapidly bleeding upper GI site
  • Continued/recurrent bleeding risk: actively bleeding/large varix, high Childs-Pugh severity score, infection, renal failure
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Anemia: Hemoglobin may be normal in active bleeding; may require 6 to 24 hours to equilibrate; other causes of anemia are common in cirrhotics.
  • Thrombocytopenia: most sensitive and specific lab parameter, correlates with portal hypertension, large esophageal varices
  • Abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin; prolonged PT, low albumin suggest cirrhosis (4).
  • BUN, creatinine (BUN often elevated in GI bleed)
  • Esophagogastroduodenoscopy (3)[A]
    • Can identify actively bleeding varices as well as large varices and stigmata of recent bleeding
    • Can treat bleeding with esophageal band ligation (preferred to sclerotherapy); prevent rebleeding; detect gastric varices, portal hypertensive gastropathy; diagnose alternative bleeding sites
    • Can identify and treat nonbleeding varices appearing as protruding submucosal veins in the distal third of the esophagus
Diagnostic Procedures/Other
  • HVPG >10 mm Hg: significant portal hypertension (normal: 1 to 5 mm Hg) (3)[A]
  • Video capsule endoscopy screening: may be an alternative for those unwilling to undergo screening endoscopy
  • Doppler sonography (second line): demonstrates patency, diameter, and flow in portal and splenic veins, and collaterals; very sensitive for gastric varices; documents patency after ligation or transjugular intrahepatic portosystemic shunt (TIPS).
  • MRI (second line, not routine): demonstrates large vascular channels in abdomen, mediastinum; demonstrates patency of intrahepatic portal and splenic vein
    • Venous-phase celiac arteriography: demonstrates portal vein and collaterals; diagnoses hepatic vein occlusion
    • Portal pressure measurement using retrograde catheter in hepatic vein
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image TREATMENT
GENERAL MEASURES
  • Treat underlying comorbidities related to cirrhosis.
  • Variceal bleeding is often complicated by hepatic encephalopathy and infection.
  • Active bleeding (5)[A]
    • IV access, hemodynamic resuscitation
    • Type and crossmatch packed RBCs. Overtransfusion increases portal pressure and increases rebleeding risk.
    • Treat coagulopathy as necessary. Fresh frozen plasma may increase blood volume and increase rebleeding risk.
    • Avoid sedation, monitor mental status, and avoid nephrotoxic drugs and &bgr;-blockers acutely.
    • Thiamine replacement as indicated, monitor blood glucose, risk for alcohol withdrawal, and delirium tremens
    • IV octreotide to lower portal venous pressure as adjuvant to endoscopic management. IV bolus of 50 &mgr;g followed by drip of 50 &mgr;g/hr.
    • Terlipressin (alternative): 2 mg q4h IV for 24 to 48 hours, then 1 mg q4h
    • Urgent upper GI endoscopy for diagnosis and treatment
      • Variceal band ligation preferred to sclerotherapy for bleeding varices. Also for nonbleeding medium-to-large varices to decrease bleeding risk
      • Ligation: lower rates of rebleeding, fewer complications, more rapid cessation of bleeding, higher rate of variceal eradication.
  • Repeat ligation/sclerosant for rebleeding.
  • If endoscopic treatment fails to stop bleeding, consider per oral placement of Sengstaken-Blakemore-type tube to stabilize patient for TIPS.
  • As many as 2/3 of patients with variceal bleeding develop an infection, most commonly spontaneous bacterial peritonitis, UTI, or pneumonia. Antibiotic prophylaxis with oral norfloxacin 400 mg or IV ceftriaxone 1 g q12h for up to a week.
  • In active bleeding, avoid &bgr;-blockers, which decrease BP and blunt the physiologic increase in heart rate during acute hemorrhage.
  • Prevent recurrence of acute bleeding
    • Vasoconstrictors: terlipressin, octreotide (reduce portal pressure)
    • Endoscopic band ligation (EBL): if bleeding recurs/portal pressure measurement shows portal pressure remains >12 mm Hg
    • TIPS: Second-line therapy if above methods fail; TIPS decreases portal pressure by creating communication between hepatic vein and an intrahepatic portal vein branch.
MEDICATION
Primary prevention of variceal bleeding (6)[A]
  • Endoscopy: assesses variceal size, presence of red wale sign (longitudinal variceal reddish streak that suggests either a recent bleed or a pending bleed) to determine risk stratification
    • Endoscopy every 2 to 3 years if cirrhosis but no varices; every 1 to 2 years if small varices and not receiving &bgr;-blockers
First Line
  • (Not actively bleeding). Nonselective &bgr;-blockers reduce portal pressure and decrease risk of first bleed from 25% to 15% in primary prophylaxis. Used in cirrhosis with small varices and increased hemorrhage risk, as well as cirrhosis + medium-to-large varices (6)[A]
    • Propranolol: 20 mg BID increase until heart rate decreased by 25% from baseline
    • Nadolol 80 mg daily; increase as above
    • Contraindications: severe asthma
  • Chronic prevention of rebleeding (secondary prevention): Nonselective &bgr;-blockers and EBL reduce rate of rebleeding to a similar extent, but &bgr;-blockers reduce mortality, whereas ligation does not (7)[A].
Second Line
Obliteration of varices with esophageal banding for those intolerant of medication prophylaxis
  • During ligation: proton pump inhibitors, such as lansoprazole 30 mg/day, until varices obliterated
ISSUES FOR REFERRAL
Referral considerations include endoscopy, liver transplantation, and interventional radiology for TIPS.
ADDITIONAL THERAPIES
Patients should receive pneumococcal vaccine and hepatitis A/B virus (HAV/HBV) vaccine.
SURGERY/OTHER PROCEDURES
  • Esophageal transection: in rare cases of uncontrollable, exsanguinating bleeding
  • Liver transplantation
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Inpatient for acute bleeding and hemodynamic stabilization, therapeutic endoscopy. ICU care is the most appropriate initially.
Discharge Criteria
Bleeding cessation; hemodynamic stability and appropriate treatment plan for comorbidities
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Close monitoring of vital signs.
  • Endoscopic variceal ligation, repeated every 1 to 4 weeks until varices eradicated
  • If TIPS, repeat endoscopy for rebleeding.
  • Endoscopic screening in patients with known cirrhosis every 2 to 3 years; yearly in patients with decompensated cirrhosis
PATIENT EDUCATION
National Digestive Information Clearinghouse, (http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/Pages/default.aspx) or American Liver Foundation, (http://www.liverfoundation.org/)
PROGNOSIS
  • Depends on underlying comorbidities
  • In cirrhosis, 1-year survival is 50% for those surviving 2 weeks following a variceal bleed.
  • In-hospital mortality remains high related to severity of underlying cirrhosis, ranging from 0% in Child A to 32% in Child C disease (5).
  • Prognosis in noncirrhotic portal fibrosis is better than for cirrhotics.
REFERENCES
1. Asrani SK, Kamath PS. Natural history of cirrhosis. Curr Gastroenterol Rep. 2013;15(2):308.
2. Pinto RB, Schneider AC, da Silveira TR. Cirrhosis in children and adolescents: an overview. World J Hepatol. 2015;7(3):392-405.
3. de Franchis R, Dell'Era A. Invasive and noninvasive methods to diagnose portal hypertension and esophageal varices. Clin Liver Dis. 2014;18(2):293-302.
4. Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014;98(1):1-16.
5. Herrera JL. Management of acute variceal bleeding. Clin Liver Dis. 2014;18(2):347-357.
6. Simonetto DA, Shah VH, Kamath PS. Primary prophylaxis of variceal bleeding. Clin Liver Dis. 2014;18(2):335-345.
7. Albillos A, Tejedor M. Secondary prophylaxis for esophageal variceal bleeding. Clin Liver Dis. 2014;18(2):359-370.
Additional Reading
&NA;
  • Kochhar GS, Navaneethan U, Hartman J, et al. Comparative study of endoscopy vs. transjugular intrahepatic portosystemic shunt in management of gastric variceal bleeding. Gastroenterol Rep (Oxf). 2015;3(1):75-82.
  • Zanetto A, Senzolo M, Ferrarese A, et al. Assessment of bleeding risk in patients with cirrhosis. Curr Hepatol Rep. 2015;14(1):9-18.
See Also
&NA;
Cirrhosis of the Liver; Portal Hypertension
Codes
&NA;
ICD10
  • I85.00 Esophageal varices without bleeding
  • I85.01 Esophageal varices with bleeding
  • I85.10 Secondary esophageal varices without bleeding
Clinical Pearls
&NA;
  • Cirrhosis is the most common underlying cause of esophageal variceal bleeding.
  • In acute bleeding, avoid &bgr;-blockers, which decrease BP and blunt the physiologic increase in heart rate.
  • In acute bleeding, overtransfusion can elevate portal pressure and increases bleeding risk.
  • Thrombocytopenia is the most sensitive marker of increased portal pressure, large esophageal varices.
  • During bleeding, consider antibiotic prophylaxis for spontaneous peritonitis and other infections with IV ciprofloxacin or oral norfloxacin for 7 to 10 days.