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 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
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; 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
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 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
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, 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.
- 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 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 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 baseline
- Nadolol 80 mg daily; increase as above
- Contraindications: 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.