gastroesophageal varices amreen m. dinani md, frcpc vtsgna fall conference october 24, 2015
TRANSCRIPT
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Gastroesophageal Varices
Amreen M. Dinani MD, FRCPCVTSGNA Fall Conference
October 24, 2015
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Objectives
• Understand the pathophysiology of portal hypertension and development of gastroesophageal varices
• Recognize and identify risk factors for developing gastroesophageal varices
• Understand the major principles in the management of gastroesophageal varices
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Case 1
AST 56 ALT 42 Tbil 1.0 ALP 76 GGT 60INR 1.4Lipid Panel: Chol 230, TG 200, LDL 151, HDL 32
6.0
15.6 110135
4.0
109
23
12
1.0136
• 45M referred to your clinic for Hepatitis C treatment. Asymptomatic
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Case 1
• In addition to starting treatment for HCV, he undergoes an upper endoscopy as you believe he has cirrhosis
• Upper endoscopy reveals:
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Question 1
• What is the next step?1. Start a beta blocker2. Do nothing 3. Repeat upper endoscopy in 1 year4. Repeat upper endoscopy in 3 years5. Recommend endoscopic band ligation
(EBL)6. Recommend TIPS
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Question 2
• What are risk factors for development of GEV?1. Presence of ascites 2. Cirrhosis secondary to alcohol3. Cirrhosis secondary to Hepatitis C4. Child’s Pugh Score B/C5. Presence of red wale signs
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Cirrhosis
Resistance to portal flow
Varices
Portal PressurePortal blood
inflow
Splanchnic arteriolar resistance
Variceal GrowthRupture
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Natural History Of Varices
No varices Small varices Large varices
7-8%/yr 7-8%/yrPredictors of development
HPVG >10mmHg AST
Groszmann et al. NEJM 2005
Predictors of progression Childs B/C
Red wale signs EtOH cirrhosis
Merli et al. Hepatology. 2003
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Variceal hemorrhage Varices with red signs Predictors of hemorrhage
Size of varices Childs B/C
Red wale signs
Groszmann et al. NEJM 2005
Bleeding risk of pts with small varices and Childs C or red wale
signs is same as moderate/large size varicesMerli et al. J Hepatology 2003
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Clinical Risk Factors For Variceal Hemorrhage
• Large esophageal varices • Appearance:
– Red wale marks– Cherry red spots – Diffuse erythema
• Childs-Pugh Class C cirrhosis• Presence of tense ascites- sign of portal
hypertension
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High Risk Stigmata
Red wale sign
Cherry red spot
Nipple sign
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Prevention of Varices/Variceal Bleeding
No varices
Small varicesNo hemorrhage
Large or high-risk small varices No hemorrhage
Variceal hemorrhage
Prevention of varices
Prevention of growth
Prevention of 1st growth
Prevention of recurrence
Pre-primary prophylaxis
Secondary prophylaxis
Primary prophylaxis
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Non-Selective Beta-Blockers DO NOT Prevent Development Of Varices
More severe side effects (18% vs 6%)
n= 108n= 105
Groszmann RJ, Garcia-Tsao et al. NEJM 2005
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HVPG Was Not Significantly Different Between Study Groups
Groszmann RJ, Garcia-Tsao et al. NEJM 2005
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Baseline HVPG is the STRONGEST Predictor for Development of Varices
Groszmann RJ, Garcia-Tsao et al. NEJM 2005
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Development Of Large Varices In Patients With No Or Small Varices At Baseline
2 years 3 years Small varices0
10
20
30
40
50
60
PlaceboPropanolol
% pts with large varices
- One third of patients lost to follow up- High risk small varices?
<0.05 NSNS
Cales et al. Eur J Gastroenterol Hepatol 1999;11:741-747
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Nadolol vs. Placebo In Patients With Small (not high-risk) Varices
Variceal Hemorrhage Survival
Merkel et al. Gastroenterology 2004
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Recommendations- Pre-primary prophylaxis
No varices
Small varicesNo hemorrhage
Large or high-risk small varices No hemorrhage
Variceal hemorrhage
No β-blockersRepeat EGD in 2-3yrs
Consider β-blockers- ββ-> no repeat EGD
- No -> repeat endoscopy in 1-2yrs
Prevention of 1st growth
Prevention of recurrence
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Primary Prophylaxis
• Prevention of variceal bleeding in a patient who has never bled previously
• 1st line of treatment– Non-selective beta blockers (nadolol,
propranol, carvedilol) OR– Endoscopic Band Ligation (EBL)
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Primary Prophylaxis- Beta Blockers
• Mechanism of action: Blocks vasodilatory β-adrenergic receptors permitting unopposed α-adrenergic vasoconstriction in the mesenteric arterioles-> reducing portal venous inflow and pressure
• Reduce risk of bleeding from 25% to 15% compared to placebo
• Best predictor of response to ββ is sustained reduction in HVPG < 12mmHg
• Clinically- 25% reduction in HR, but not less than 55 beats/min– Only 20-30% of subjects achieve the goal HR– 15-20% of subjects cannot tolerate ββ
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Primary Prophylaxis- Band Ligation
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Meta-Analysis Of Trials of EBL vs ββ For Primary Prophylaxis
Best Prac Res Clin Gastroenterol 2007;21:31-42
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Cirrhosis
Resistance to portal flow
VaricesVariceal growthVariceal rupture
Portal PressurePortal blood
inflow
Splanchnic arteriolar resistance
Non-selective β-blockers
Β-2 blockade
Β-1 blockade
Cardiac output
PropanololNadolol
Coreg-- nonselective beta blocker/alpha-1 blocker
Unable to tolerate BB-> EBL
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Recommendations- Primary Prophylaxis
No varices
Small varicesNo hemorrhage
Large or high-risk small varices No hemorrhage
Variceal hemorrhage
No β-blockersRepeat EGD in 2-3yrs
Consider β-blockers- ββ-> no repeat EGD
- No -> repeat endoscopy in 1-2yrs
High risk stigmata- nonselective β-blockers OR EVL
No high risk stigmata- Non-selective β-blockers preferred
Combination of nonselective β-blockers plus EVL
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Case 2
• 45M presents with a several hour history of hematemesis. His history is significant for long standing alcoholism
• PE: Tachycardia of 110 and SBP of 90• Labs on admission: Hgb of 10, plt 100,000 and
INR of 2.0
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Question 3
• What would you do next?1. Call GI for an urgent upper endoscopy 2. Start Nexium ggt, 2 units PRBC 3. Call IR for urgent TIPS 4. Intubate the patient and stabilize 5. Start Nexium ggt, Octreotide ggt, 2 unit PRBC
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Active Variceal HemorrhageGeneral Measures
• Airway protection• Gastric aspiration• Hemodynamic resuscitation
– Blood, crystalloid (avoid over-transfusion)– FFP, platelets are usually not necessary
• Antibiotics • Metabolic support
– Thiamine, DT’s monitoring, glucose/lytes
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45-day mortality with Hgb goal >7 g/dl
Villanueva C et al. N Engl J Med 2013;368:11-21
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Death by 6 weeks
Villanueva C et al. N Engl J Med 2013;368:11-21
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Thresholds For Transfusion
• 9.0 g/dl for SBP <100, HR>100 – NO DATA
• 10 g/dl with concomitant cardiac sx’s– SOME DATA
• 7.0 g/dl or less for everyone else– International Consensus Recommendation– RECENT GOOD DATA
Barkun AN et al. Annals Intern Med 2010;152:101-113
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Antibiotic Prophylaxis Improves Mortality
Overall Mortality Mortality due to Bacterial Infections
Chavez-Tapia NC et al. Aliment Pharmacol Ther. 2011;34(5):509-18
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Pharmacologic Therapy in Active Variceal Hemorrhage
• Vasopressin– Causes splanchnic vasoconstriction reducing portal
venous inflow and reducing portal pressure– Has severe toxicity (cardiac, bowel ischemia)
• Terlipressin– Semisynthetic analog of vasopressin– Less side effects than vasopressin– Evaluated in at least 20 clinical trials– Shown to increase survival in variceal bleeding– Not available in US
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Pharmacologic Therapy in Active Variceal Hemorrhage
• Somatostatin– Decreases portal pressure and collateral blood
flow by inhibiting release of glucagon– Also reduces post prandial mesenteric blood flow– Not available in the US– Half life in circulation of 1-3 minutes
• Octreotide– Somatostatin analog– Half life of 80-120 minutes– Effect on portal pressure is not prolonged– Several studies have shown it to be superior to
placebo in controlling variceal hemorrhage
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Endoscopic Therapy for Acute Variceal Hemorrhage
• EVL- Preferred endoscopic modality for control of acute esophageal variceal bleeding and for prevention of rebleeding
• Varices at the GE junction are banded initially, and then more proximal varices are banded in a spiral manner about every 2 cms
• 80-90% of patients will stop bleeding with EVL and octreotide
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Endoscopic Variceal Ligation
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Factors Associated With Failure To Control Acute Hemorrhage• Spurting varices• High Child-Pugh score• High HVPG• Infection• Portal Vein Thrombosis
Factors Associated with Early Rebleeding
• Severe initial bleeding• Overly aggressive
volume resuscitation• Infection• High HVPG• Complications of
endoscopic therapy• Renal failure
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Secondary Prophylaxis
• Preventing hemorrhage in patients with a history of variceal hemorrhage
• After an index bleed, 70% of patients experience recurrent variceal hemorrhage within one year
• 1st line of treatment: EVL and ββ
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EVL + Nadolol vs. EVL
0
5
10
15
20
25
30
Rebleeding Survival
EVL + N
EVL
** p<.006
Hepatology 2005;41(3):572-8
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Secondary Prophylaxis Summary
• EVL and ββ • EVL every 2-3 weeks until varices eradicated• Once eradicated -> Upper endoscopy + EVL
every 3 to 6 months for treatment of recurrent varices
• TIPS if pharmacologic and endoscopic therapy fail
• Liver transplant referral- 60% mortality at 1 yr
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Recommendations- Primary and Secondary Prophylaxis
No varices
Small varicesNo hemorrhage
Large or high-risk small varices No hemorrhage
Variceal hemorrhage
No β-blockersRepeat EGD in 2-3yrs
Consider β-blockers- ββ-> no repeat EGD
- No -> repeat endoscopy in 1-2yrs
High risk stigmata- nonselective β-blockers OR EVL
No high risk stigmata- Non-selective β-blockers preferred
Combination of nonselective β-blockers plus EVL
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Case 3• 43F with alcoholic liver disease presents with
hematemesis• VS 90/50 HR 110• Somnolent, somewhat confused• Spider angiomas on chest• Hgb 10, plt 64, INR 2.3, Alb 2.1, TB 3.2, AST 85,
ALT 26• Childs Pugh Class C on admission
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What worrisome features does this patient have that puts her at high risk of rebleeding or difficult to control?
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Treatment of Early Rebleeding or Uncontrolled Active Bleeding
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Early Use Of TIPS In Patients With Cirrhosis and Variceal Bleeding
Inclusion Criteria• Cirrhosis with acute variceal hemorrhage• Treated with vasoactive drugs, endoscopic
therapy and antibiotics.• Child-Pugh class C (10-13) or Child Pugh class B
(7-9) with active bleeding• More than 10 Child-Pugh points excluded
Garcia-Pagan, et al. NEJM 2010;362:2370-2378
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Probability of Remaining Free of Bleeding and of Survival
Garcia-Pagan, et al. NEJM 2010;362:2370-2378
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Conclusion
• First priority: Hemodynamic stability and resuscitation • No role for pharmacological therapy to prevent
varices • Non-selective beta blockers preferred over EVL for
primary prophylaxis • Treat infections aggressively • Presence of ascites- indicative of portal hypertension • Rescue measures: Blakemore/Minnesota Tube and
TIPS +/- liver transplant referral