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Esophageal Varices

- 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

- 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

- 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, avoid nephrotoxic drugs and β-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 μg followed by drip of 50 μg/hour. - 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.

- (Not actively bleeding). Nonselective β-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

para>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 HCVLess common: hemochromatosis, hepatitis B, nonalcoholic fatty liver disease, primary biliary cirrhosis and autoimmune cirrhosis
  • Noncirrhotic portal hypertensionExtrahepatic portal or splenic vein thrombosis, trauma, chronic pancreatitis, thrombotic disease, polycythemiaMetastasis to liver sinusoids/portal vein: lymphoma, leukemia, hepatoma, or other carcinomasMetabolic 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

DIAGNOSIS

  • First indication of varices often associated with GI bleeding episode: painless hematemesis, hematochezia, and/or melena
  • Occult bleeding (anemia): uncommon

HISTORY

  • Underlying history of cirrhosis/liver disease. Variceal bleed can be initial presentation of previously undiagnosed cirrhosis.
  • Alcoholism, exposure to blood-borne viruses
  • Hematemesis, melena, or hematochezia
  • Rapid upper GI bleed can present as rectal bleeding.

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

DIAGNOSTIC TESTS & INTERPRETATION

  • Upper GI bleeding: 10-30% are due to varices.In patients with known varices, as many as 50% bleed from nonvariceal sources.Peptic ulcer; gastritisGastric/esophageal malignancyCongestive gastropathy of portal hypertensionArteriovenous malformationMallory-Weiss tearsAortoenteric fistulaHemoptysis; nosebleed
  • Lower GI bleedingRectal varices; hemorrhoidsColonic neoplasiaDiverticulosis/arteriovenous malformationRapidly bleeding upper GI site
  • Continued/recurrent bleeding risk: actively bleeding/large varix, high Childs-Pugh severity score, infection, renal failure

DIFFERENTIAL DIAGNOSIS

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 bleedingCan treat bleeding with esophageal band ligation (preferred to sclerotherapy); prevent rebleeding; detect gastric varices, portal hypertensive gastropathy; diagnose alternative bleeding sitesCan 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 veinVenous-phase celiac arteriography: demonstrates portal vein and collaterals; diagnoses hepatic vein occlusionPortal pressure measurement using retrograde catheter in hepatic vein

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 resuscitationType 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, avoid nephrotoxic drugs and β-blockers acutely.Thiamine replacement as indicated, monitor blood glucose, risk for alcohol withdrawal, and delirium tremensIV octreotide to lower portal venous pressure as adjuvant to endoscopic management. IV bolus of 50 μg followed by drip of 50 μg/hour.Terlipressin (alternative): 2 mg q4h IV for 24 to 48 hours, then 1 mg q4hUrgent upper GI endoscopy for diagnosis and treatmentVariceal band ligation preferred to sclerotherapy for bleeding varices. Also for nonbleeding medium-to-large varices to decrease bleeding riskLigation: 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 β-blockers, which decrease BP and blunt the physiologic increase in heart rate during acute hemorrhage.
  • Prevent recurrence of acute bleedingVasoconstrictors: terlipressin, octreotide (reduce portal pressure)Endoscopic band ligation (EBL): if bleeding recurs/portal pressure measurement shows portal pressure remains >12 mm HgTIPS: 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 stratificationEndoscopy every 2 to 3 years if cirrhosis but no varices; every 1 to 2 years if small varices and not receiving β-blockers

First Line

  • (Not actively bleeding). Nonselective β-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 baselineNadolol 80 mg daily; increase as aboveContraindications: severe asthma
  • Chronic prevention of rebleeding (secondary prevention): Nonselective β-blockers and EBL reduce rate of rebleeding to a similar extent, but β-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

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.

COMPLICATIONS

  • Formation of gastric varices or varices in other uncommon locations may occur after eradication of esophageal varices.
  • Esophageal varices can recur.
  • Hepatic encephalopathy, renal dysfunction, hepatorenal syndrome
  • Infections are common after banding/ligation of varices.

REFERENCES

11 Asrani SK, Kamath PS. Natural history of cirrhosis. Curr Gastroenterol Rep. 2013;15(2):308.22 Pinto RB, Schneider AC, da Silveira TR. Cirrhosis in children and adolescents: an overview. World J Hepatol. 2015;7(3):392-405.33 de Franchis R, Dell"Era A. Invasive and noninvasive methods to diagnose portal hypertension and esophageal varices. Clin Liver Dis. 2014;18(2):293-302.44 Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014;98(1):1-16.55 Herrera JL. Management of acute variceal bleeding. Clin Liver Dis. 2014;18(2):347-357.66 Simonetto DA, Shah VH, Kamath PS. Primary prophylaxis of variceal bleeding. Clin Liver Dis. 2014;18(2):335-345.77 Albillos A, Tejedor M. Secondary prophylaxis for esophageal variceal bleeding. Clin Liver Dis. 2014;18(2):359-370.

ADDITIONAL READING

  • 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

Cirrhosis of the Liver; Portal Hypertension

CODES

ICD10

  • I85.00 Esophageal varices without bleeding
  • I85.01 Esophageal varices with bleeding
  • I85.10 Secondary esophageal varices without bleeding
  • I85.11 Secondary esophageal varices with bleeding

ICD9

  • 456.1 Esophageal varices without mention of bleeding
  • 456.0 Esophageal varices with bleeding
  • 456.20 Esophageal varices in diseases classified elsewhere, with bleeding
  • 456.21 Esophageal varices in diseases classified elsewhere, without mention of bleeding

SNOMED

  • 28670008 Esophageal varices (disorder)
  • 14223005 Esophageal varices without bleeding
  • 17709002 Bleeding esophageal varices (disorder)
  • 195474004 Esophageal varices associated with another disorder
  • 195476002 Esophageal varices without bleeding, associated with another disorder
  • 195475003 Esophageal varices with bleeding, associated with another disorder

CLINICAL PEARLS

  • Cirrhosis is the most common underlying cause of esophageal variceal bleeding.
  • In acute bleeding, avoid β-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.