• Information
  1. Pathophysiology
  2. Diagnosis
  3. Treatment Overview
  4. Prophylaxis Against Initial Variceal Bleeding
  5. Prevention of Rebleeding Episodes
  6. Transjugular Intrahepatic Portosystemic Stent-Shunt
  7. Acute Variceal Bleeding
  8. Surgical Shunt Procedures
  9. Prognosis

A. Pathophysiology

1. Cirrhosis is a fibrotic disease of the liver, with hepatocyte regeneration
2. Presence of fibrotic (connective) tissue throughout liver impedes blood flow
   1. Result is increase in pressures required to perfuse the liver
   2. Accentuated by imbalance between endothelin-1 and nitric oxide (vasodilator)
3. These increased pressures cause portal hypertension (HTN)
   1. Result of portal HTN is also increased flow "around" liver
   2. Varices are dilated veins that form in response to increased "liver-bypass" blood flow
   3. Varices tend to be quite superficial and bleed easily
   4. Other causes of portal HTN (such as portal vein thrombosis) cause formation of varices
4. Variceal hemorrhage occurs in ~30% of patients with cirrhosis
5. In patients with cirrhosis, ~85% of gastrointestinal bleeding is variceal bleeding
   1. ~30% of initial bleeding episodes are fatal
   2. 1 year survival after variceal hemorrhage is ~30%

B. Diagnosis

1. All patients with cirrhosis should be screened for presence of varices
2. Barium esophagogram (barium swallow) may be sufficient
3. Upper endoscopy is most sensitive but is invasive

C. Treatment Overview [1]

1. Prevention of first bleed in patients with varices
2. Treatment of acute bleeding
3. Prevention of rebleeding
4. In all settings, reduction of portal pressures reduces risk of bleeding and bleeding rate
5. Variceal bleeding is a medical emergency with a high mortality risk

D. Prophylaxis Against Initial Variceal Bleeding

1. Risk Factors for Initial Bleed
   1. Poor liver function
   2. Continued alcohol use
   3. Large varices
   4. Increasing venous pressure gradient (invasive, not usually used)
2. Prophylaxis reduce the risk of initial bleeding
   1. Decreasing portal pressures reduces risk of first bleeding event but does not appear to prevent the development of varices in patients with cirrhosis [11]
   2. Band ligation appears to be superior to medical therapy for primary prevention of bleeding in patients with large esophageal varices [2,3]
   3. In lower risk patients, medicines are excellent initial choices for prophylaxis
3. Medications for Reduction of Portal Pressure
   1. Non-selective ß-adrenergic blocking agents
   2. Nitrates
4. Non-Selective ß-Blockers [4]
   1. Reduce splanchnic blood pressure, portal pressure, and collateral blood flow
   2. Propranolol and naldolol prolong time to first variceal bleed
   3. They have less of an effect on time until second (re-) bleed
   4. ß-Blocker dose should be increased until heart rate decreases by ~25%
   5. Initial dose of propranolol in most patients is 40mg po qd (titrate every 24 hours)
   6. ß-blockers do not prevent development of varices in cirrhotic patients with portal HTN [11]
5. Nitrates
   1. Isosorbide mononitrate 20mg tid is as effective as propranolol at prevention of rebleed
   2. Isosorbide mononitrate combined with naldolol was more effective than sclerotherapy in prevention of second (re-) bleed [5]
   3. Goal is >20% reduction in portal pressures, which significantly reduces rebleed risk
6. Ursodiol treatment of primary biliary cirrhosis patients reduces risk of developing new esophageal varices (from 58% with placebo to 16% in treated group) [7]
7. Endoscopic ligation of varices is acceptable over medical therapy high risk patients [1,2]

E. Prevention of Rebleeding Episodes

1. Prognosis in Patients with Rebleeding
   1. Occurrence of an esophageal variceal hemorrhage predicts high short term mortality
   2. Over 65% of patients with initial variceal bleed will have recurrent hemorrhage
   3. Recurrent hemorrhage usually occurs within 6 months of initial hemorrhage
2. Reduction of rebleeding rates is the major goal of therapy
3. Combinations of endoscopic and drug therapy to prevent variceal rebleeding in patients with cirrhosis are >30% superior to either treatment alone [6]
4. Overview of Therapy to Prevent First Variceal Bleed
   1. Medications: ß-blockers, nitrates
   2. Esophageal Band Ligation preferred over Sclerotherapy [3]
   3. Transjugular intrahepatic portosystemic shunt (TIPS)
   4. Consider additional prophylaxis with H-2 Blockers (such as famotidine 20mg po/iv bid)
5. Medications
   1. ß-adrenergic blockers are very effective for preventing initial bleed in patients with varicense (see above)
   2. ß-blockers are not very effective for prevention of rebleeding
   3. Isosorbide mononitrate combined with naldolol was more effective than sclerotherapy in prevention of second (re-) bleed [5]
   4. Isosorbide mononitrate combined with nadolol is more effective than endoscopic ligation for prevention of second (re-) bleed [8]
   5. Combination isosorbide with ß-blockers does not improve mortality [1]
6. Band Ligation and Sclerotherapy
   1. For severe, symptomatic varices
   2. Prophylaxis with sclerotherapy associated with increased mortality in most studies
   3. Endoscopic ligation preferred to sclerotherapy for therapy of bleeding varices [9]
   4. Ligation should be combined with octreotide (or vasopressin) for 48 hours [10]
   5. Sclerotherapy has shown mortality benefit in patients who have had a first bleed
   6. Long term followup showed low rebleeding rates, even with chronic sclerotherapy [12]
   7. Most patients (70%) required repeat sclerotherapy within one year of initial therapy [12]
7. Sclerotherapy and TIPS appear to be identical with respect to various outcomes [13,14]
8. Rebleeding Rates at 12 Months [1]
   1. Medical Therapy 4-25%
   2. Endoscopic Variceal Band Ligation 20-30%
   3. TIPS (See below) 8-15%
   4. Surgical distal splenorenal shunt (or variation) 5-10%

F. Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPS) [15,16]

1. Indications
   1. Portal hypertension with ascites
   2. Recurrent variceal bleeding in patients with cirrhosis
   3. TIPS has largely replaced open surgical shunt proceedures
2. Description
   1. Conduit from portal vein to hepatic vein (IVC) placed transvenously
   2. Internal jugular vein entered and catheter advanced through IVC into R hepatic vein
   3. Intraheptic branch of portal vein is punctured seperately to establish a shunt
   4. Stent is placed (tubular wire mesh) to form shunt tract
   5. High success rates generally reported (90-100%) for placement
   6. Hemorrhage is major complication (~10%)
   7. Stenosis or occlusion of stent may occur (~20% in 6 months initially)
3. Efficacy
   1. Safe and effective therapy for variceal bleeding by reducing portal pressure [17]
   2. Overall similar to sclerotherapy for preventing rebleeds and survival [13,14,18]
   3. Significantly reduces ascites formation with >70% complete response in 3 months [17]
   4. Lttle effect on albumin, PT, or bilirubin levels, but creatinine usually improves
   5. Cardiac and renal status may be impaired, at least acutely; natriuresis occures late [19]
   6. TIPSS induces a natriuresis and systemic vasodilation, with mild renal improvement
4. Poor Outcome [20]
   1. Patients may develop severe hyperbilirubinemia
   2. These patients have a very poor prognosis: death or transplant in 95% within 90 days
   3. Patients with a pre-TIPS PT time >17 seconds have greatest risk for poor outcome
   4. In addition, non-alcoholic liver disease etiology linked to need for TIPS also high risk

G. Acute Variceal Bleeding

1. Variceal hemorrhage is a medical emergency with high mortality
2. Medical and/or surgical therapy is almost universally required to halt bleeding
3. Reversal of coagulopathy associated with liver failure is critical
4. Medications to Slow Hemorrhage
   1. Vasopressin was originally the mainstay of therapy, causing vasoconstriction
   2. Nitroglycerin iv is often given along with vasopressin to prevent cardiac ischemia
   3. However, octreotide or terlipressin are first line therapy in acute bleeding [1]
   4. Octreotide (Sandostatin®) IV reduces rebleeding ~90% combined with variceal ligation [10]
   5. Octreotide acutely reduces rebleeding more than vasopressin or terlipressin [21]
   6. Another somatostatin analog, vapreotide, reduces bleeding by 65% but not survival [22]
   7. In a meta-analysis, octreotide did not increase survival or reduce blood transfusion [23]
   8. Pharmacologic agents are followed by urgent endoscopic therapy
5. Invasive Procedures
   1. Endoscopic sclerotherapy was recent mainstay of minimally invasive therapy
   2. Endoscopy with ligation (banding) of varices is now perferred over sclerotherapy
   3. Octreotide or vapreotide combined with sclerotherapy is better than sclerotherapy alone for controlling bleeding, but provided no improvement in short term mortality [22,24]
   4. Natural somatostatin combined with sclerotherapy reduced acute bleeding episodes [25]
   5. Octreotide should be continued for 1-2 days after endoscopy
   6. Balloon tamponade can also be used to temporarily halt bleeding
   7. Surgical correction of bleeding varices may be required in refractory cases
   8. TIPSS Procedure is considered once patient is stabilized (see below)
6. Systemic antibiotics should be given to reduce the risk infection during bleeding

H. Surgical Shunt Procedures

1. These procedures provide shunt between mesenteric (portal) and systemic circulation
2. Bypass liver, lower portal hypertension, ascites formation, esophageal bleeding
3. Hepatic encephalopathy is nearly always increased
4. These procedures have fallen out of favor as TIPS and endoscopic protocols are used
5. Surgery is often complicated by cirrhotic coagulopathy

I. Prognosis

1. Overall Mortality [15]
   1. In patients with esophageal varices, 1 year survival was ~90%
   2. Two year survival was ~80%
2. Surgery versus Sclerosis [19]
   1. Mortality elevated in surgical therapy compared with sclerosis with first variceal bleed
   2. These were Child Grade A and B (mild and moderate) varices
   3. Rebleeding slightly higher in sclerosed patients though not generally significant
   4. In-hospital morbidity much higher with surgical patients
3. Combined endoscopic and drug therapy for preventing rebleeds of esophageal varices showed a trend towards reduced mortality veruses either therapy alone [6]

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