Evidence-Base Management of Esophageal and Gastric Varices Rino Alvani Gani Hepatobiliary Division Department of Internal Medicine Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo National General Hospital
Chronic Liver Disease Chronic liver disease Compensated cirrhosis Decompensated cirrhosis Death Emergence of complications: Ascites Hepatic encephalopathy Icterus Esophageal & gastric varices
Liver cirrhosis Portal systemic colateral Increased resistance due to sinusoid disturbance Portal vein Splenomegaly
VARICES AND VARICEAL HEMORRHAGE Cirrhosis Resistance to portal flow Portal pressure Varices Variceal Growth
VARICES INCREASE IN DIAMETER PROGRESSIVELY VARICES INCREASE IN DIAMETER PROGRESSIVELY No varices Small varices Large varices
PREVENTION OF VARICEAL DEVELOPMENT TREATMENT OF VARICES / VARICEAL HEMORRHAGE No varices Prevention of variceal development Varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
NON-SELECTIVE BETA BLOCKERS DO NOT PREVENT DEVELOPMENT OF VARICES PRE-PRIMARY PROPHYLAXIS Multicenter, randomized, placebo-controlled trial of timolol (non-selective beta-blocker) vs. Placebo in patients Beta-blockers did not prevent the development of varices and were associated with a higher rate of serious adverse events Hepatic venous pressure gradient was the strongest predictor of the development of varices
MANAGEMENT OF PATIENTS WITHOUT VARICES Treatment of Varices / Variceal Hemorrhage No varices No specific therapy Repeat endoscopy in every 2-3 yrs Varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
PREVENTION OF FIRST VARICEAL HEMORRHAGE Treatment of Varices / Variceal Hemorrhage No varices Varices No hemorrhage Variceal hemorrhage Prevention of first variceal hemorrhage Recurrent hemorrhage
MANAGEMENT OF PATIENTS WITH VARICES WHO HAVE NEVER BLED Treatment of Varices / Variceal Hemorrhage No varices Varices No hemorrhage Management depends on the size of varices Variceal hemorrhage Recurrent hemorrhage
MANAGEMENT OF PATIENTS WITH SMALL VARICES WITHOUT PRIOR HEMORRHAGE Treatment of Varices / Variceal Hemorrhage No varices Varices No hemorrhage? Prevention of variceal growth Variceal hemorrhage Recurrent hemorrhage
MANAGEMENT OF PATIENTS WITH SMALL VARICES WITHOUT PRIOR HEMORRHAGE Treatment of Varices / Variceal Hemorrhage No varices Varices No hemorrhage Repeat endoscopy in 1-2 years Beta-blockers? Variceal hemorrhage Recurrent hemorrhage
MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGE Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage Large varices No hemorrhage Variceal hemorrhage 1) -blockers (propranolol 1-2 mg/kg/day) indefinitely 2) Endoscopic variceal ligation/sclerotherapy in patients intolerant to - blockers Recurrent hemorrhage
Small varices, compensated cirrhosis Cirrhotic patients + Small varices, red sign or Decompensated cirrhosis + Small varices without red sign NSSB Sarin SK et al, Hepatol Int 2008
Patients with no varices or small varices (unchanged) There is no indication, at this time, to use beta blockers to prevent the formation of varices (1b;A) Patients with small varices with red wale marks or CP-C have an increased risk of bleeding (1b;A) and should be treated with nonselective beta blockers (5;D) Patients with small varices without signs of increased risk may be treated with NSBB to prevent bleeding (1b;A). Further studies are required to confirm their benefit.
PROPRANOLOL Decreases cardiac output resulting in decreased portal pressure and variceal size. Reduces the intrahepatic portal vascular resistance. MOST WIDELY USED β BLOCKER. Produces splanchnic vasoconstriction which leasd to decrease in portal blood flow. Used along with sclerotherapy. Benificial results in terms of lower rebleeding rates & lower variceal recurrence.
Endoscopic Variceal Band Ligation BLEEDING CONTROLLED IN 90% REBLEEDING RATE 30% COMPARED WITH SCLEROTHERAPY: Less rebleeding Lower mortality Fewer complications ENDOSCOPIC VARICEAL BAND LIGATION Fewer treatment sessions
Variceal ligation Under direct visualization through an flexible endoscope, elastic bands are applied to oesophageal or gastric varices Indications: Bleeding varices Theraupetic non-bleeding varices
EVBL appears to be superior to BB in preventing the first variceal bleed. No difference was found for mortality
Overall bleeding Funakoshi M, et al. Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of esophageal variceal bleeding. Annals of Hepatology 2012; 11 (3): 369-383
Overall mortality Funakoshi M, et al. Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of esophageal variceal bleeding. Annals of Hepatology 2012; 11 (3): 369-383
Patients with medium-large varices (unchanged) Either NSBB or endoscopic band ligation is recommended for the prevention of the first variceal bleeding of medium or large varices (1a;A) The choice of treatment should be based on local resources and expertise, patient preference and characteristics, contraindications and adverse events (5;D)
CONTROL OF ACUTE VARICEAL HEMORRHAGE Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage Medium/ large varices No hemorrhage Variceal hemorrhage Control of hemorrhage Recurrent hemorrhage
GENERAL MANAGEMENT: Iv access and fluid resuscitation Do not overtransfuse (hemoglobin ~ 8 g/dl) Antibiotic prophylaxis (iv ceftriaxone 50-100 mg/kg/day) SPECIFIC THERAPY: Pharmacological therapy: terlipressin, somatostatin and analogues, vasopressin + nitroglycerin Endoscopic therapy: band ligation, sclerotherapy Shunt therapy: tips, surgical shunt
PHARMACOLOGIC THERAPY Somatostatin-decreases portal flow, splanchnic vasoconstriction. Octreotide- 50mcg/h shown to reduce complications of bleeding after sclerotherapy. Vasopressin- reduces blood flow to all splanchnic organs, decreases portal pressure, venous blood flow. Use nitroglycerin with it! It s the most potent splanchnic vasoconstrictor. Antibiotics to prevent infection.
Terlipressin vs Placebo in Variceal Hemorrhage Meta-analysis of Terlipresin vs Placebo Results even more significant after adding the RCT by Levacher et al (Lancet, 1995)
HVPG decrease during active bleeding after somatostatin (250 vs 500 ug/h) or Terlipressin Villanueva et al. Am J Gastroenterology 2006
Gastric Varices APASL Recommendation on Management of Acute Variceal Bleeding Acute bleeding from gastric varices tissue adhesive injection is the treatment of choice (1b. A) Sarin SK et al. Hepatol Int 2011
Patients with gastric varices (changed from Baveno V) Although a single study suggested that cyanoacrylate injection is more effective than beta blockers in preventing first bleeding in patients with large gastroesophageal varices type 2 or isolated gastric varices type 1 (1b;A), further studies are needed to evaluate the risk/benefit ratio of using cyanoacrylate in this setting before a recommendation can be made
TIPS IN THE TREATMENT OF VARICEAL HEMORRHAGE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT Tips is rescue therapy for recurrent variceal hemorrhage It is only useful in portal hypertension of hepatic origin. Tips is indicated in patients who rebleed on combination endoscopic plus pharmacologic therapy In patients with cirrhosis, the distal spleno-renal shunt is as effective as tips.
ACCEPTED INDICATIONS Active bleeding despite endoscopic or pharmacologic treatment Recurrent variceal bleeding despite adequate endoscopic treatment. Potential indications include bleeding gastric fundic varices, refractory ascites. A bridge to transplantation.
Transjugular Intrahepatic Portosystemic Shunt Hepatic vein TIPS Portal vein Splenic vein Superior mesenteric vein
Polytetrafluoroethylene-covered TIPS stent
Trials comparing early TIPS and standard treatment (combines pharmaco and endoscopic therapy) in high-risk variceal bleeding Siramolpiwat S, et al. Transjugular intrahepatic portosystemic shunts and portal hypertension-related complications. World J Gastroenterol 2014; 20(45): 16996-17010
Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) Preventing gastric variceal rebleeding after endoscopic therapy or when management with endoscopic therapy fails Patel A, et al. Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices. AJR 2012; 199:721 729
BRTO (Technique) Garcia-Pagan JC, et al. Management of Gastric Varices. Clinical Gastroenterology and Hepatology 2014;12:919 928
Published reports of BRTO Patel A, et al. Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices. AJR 2012; 199:721 729
BRTO of Gastric Varices (Patel et al) Although the procedure can be performed when TIPS is contraindicated or when endoscopic management fails, it is successful as a first- or second-line therapy Patel A, et al. Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices. AJR 2012; 199:721 729
Studies Utilizing BRTO to Treat Gastric Varices BRTO utilizing STS foam appears effective in obliterating bleeding GV with good short-term outcomes Sabri SS, et al. Bleeding Gastric Varices Obliteration with Balloon- occluded Retrograde Transvenous Obliteration Using Sodium Tetradecyl Sulfate Foam. J Vasc Interv Radiol 2011; 22:309 316
Self-Expandable Metal Stents (SEMS) Were mainly used for treatment of esophageal obstruction/strictures, leaks, perforation or even tracheoesophageal fistulas. The first cases of SEMS application for esophageal variceal bleeding were reported eight years ago. SEMSs constructed for variceal bleeding have become commercially available outside of clinical studies. Muller M, et al. Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection- Therapy: A Retrospective Study. PLoS ONE 2015. 10(6): e0126525
Muller M, et al. Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection- Therapy: A Retrospective Study. PLoS ONE 2015. 10(6): e0126525
Conclusion of the study Self-expandable metal stents for esophageal variceal bleeding seem to be safe and efficient after failed standard therapy. SEMS should be considered a reasonable treatment option for refractory esophageal variceal bleeding after treatment failure of ligature and sclerotherapy or contraindication for other measures (e.g. TIPS). Muller M, et al. Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection- Therapy: A Retrospective Study. PLoS ONE 2015. 10(6): e0126525
Use of self-expandable metal stents (changed from Baveno V) Data suggest that self-expanding covered oesophageal metal stents may be as efficacious and a safer option than balloon tamponade in refractory oesophageal variceal bleeding (4;C).
Thank You
April 2015 J Hepatol 2015 ; 63 : 743 752
No varices MANAGEMENT OF PATIENTS WITH ACUTE VARICEAL HEMORRHAGE Treatment of Varices / Variceal Hemorrhage Small varices No hemorrhage Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage 1) Safe vasoactive drug + endoscopic therapy + balloon tamponade+antibiotic prophylaxis 2) TIPS / Shunt (rescue therapy)
PREVENTION OF RECURRENT VARICEAL HEMORRHAGE Treatment of Varices / Variceal Hemorrhage No varices Varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage 1) -blockers + EVL 2)TIPS / shunt surgery
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE Evolution of Varices Cirrhosis with no varices Level of Intervention Pre-primary prophylaxis Management Recommendations Repeat endoscopy in 2-3 years No specific therapy
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE Evolution of Varices Cirrhosis with no varices Small varices No hemorrhage Medium / large varices No hemorrhage Level of Intervention Pre-primary prophylaxis Primary prophylaxis Management Recommendations Repeat endoscopy in 2-3 years No specific therapy Small varices Repeat endoscopy in 1-2 years No specific therapy? beta-blocker to prevent enlargement Medium/Large varices Non-selective beta-blockers EVL in those intolerant to drugs
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE Evolution of Varices Cirrhosis with no varices Small varices No hemorrhage Medium / large varices No hemorrhage Variceal hemorrhage Level of Intervention Pre-primary prophylaxis Primary prophylaxis Management Recommendations Repeat endoscopy in 2-3 years No specific therapy Small varices Repeat endoscopy in 1-2 years No specific therapy? beta-blocker to prevent enlargement Medium/Large varices Non-selective beta-blockers EVL in those intolerant to drugs Endoscopic/pharmacologic therapy Antibiotics in all patients TIPS or shunt surgery as rescue therapy
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE Evolution of Varices Cirrhosis with no varices Small varices No hemorrhage Medium / large varices No hemorrhage Variceal hemorrhage Recurrent variceal hemorrhage Level of Intervention Pre-primary prophylaxis Primary prophylaxis Secondary prophylaxis Management Recommendations Repeat endoscopy in 2-3 years No specific therapy Small varices Repeat endoscopy in 1-2 years No specific therapy? beta-blocker to prevent enlargement Medium/Large varices Non-selective beta-blockers EVL in those intolerant to drugs Endoscopic/pharmacologic therapy Antibiotics in all patients TIPS or shunt surgery as rescue therapy Beta-blockers + EVL TIPS or shunt surgery as rescue therapy
Conclusion of the study TIPS did not increase survival rate compared with variceal band ligation It significantly reduced the incidence of variceal rebleeding without increasing the rate of encephalopathy.
PORTOSYSTEMIC SHUNTS Shunt operations are the only modalities that effectively reduce portal pressure and thus definatively treat the underlying cause of variceal bleeding. TYPES OF SHUNT OPERATIONS NON SELECTIVE SHUNTS Portocaval shunts Mesocaval shunts Splenorenal shunts SELECTIVE SHUNTS Distal splenorenal shunt
DISTAL SPLEENORENAL SHUNT