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TABLE OF CONTENTS

1. INTRODUCTION ... 16

1.1. CIRRHOSIS AND PORTAL HYPERTENSION ... 16

1.1.1. Clinical Presentation ... 17

1.1.2. Staging and Diagnosis of Chronic liver Disease and Portal Hypertension ... 18

1.1.3. Hepatic Venous Pressure Gradient Assessment ... 21

1.1.4. MELD and Child–Pugh Classification ... 22

1.1.5 Management of Portal Hypertension ... 24

1.2. ACUTE VARICEAL BLEEDING ... 28

1.2.1. Epidemiology of AVB ... 29

1.2.2. Physiopathology of AVB ... 30

1.2.3. Location of Varices ... 31

1.2.4. Size of Varices ... 32

1.2.5. Role of Endoscopy in the Diagnosis and Grading of Varices ... 34

1.2.5.1. Esophagogastroduodenoscopy (EGD) ... 34

1.2.5.2. Endoscopic Ultrasound (EUS) ... 36

1.2.5.3. Capsule Endoscopy (CE) ... 37

1.2.6. Initial Management of the Acute Bleeding Episode ... 38

1.2.7. Blood Volume Restitution ... 39

1.2.8. Antibiotic Prophylaxis ... 40

1.2.9. Pharmacological Treatment ... 41

1.2.9.1. Timing of endoscopic hemostasis ... 43

1.2.9.2. Endoscopy Management of Acute Variceal Bleeding ... 44

1.2.9.3. Endoscopic management of bleeding gastric varices ... 48

1.2.9.4. Salvage Therapy after Failure of Endoscopic Hemostasis ... 48

1.2.10. Balloon Tamponade ... 49

1.2.11. Use of Self-Expandable Metal Stents ... 49

1.2.12. Transjugular intrahepatic portosystemic shunt (TIPS) ... 50

1.2.13. Promising Treatment Modality ... 51

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2.1. Assessing the feasibility and safety of the hemostatic powder in acute esophageal variceal bleeding. 54

2.2. Assessing the efficacy and safety of the hemostatic powder in acute variceal bleeding in

combination with SOC medical and endoscopic treatment. ... 54

2.3. Evaluating the impact of the hemostatic powder as an add on therapeutic modality in combination with SOC medical and endoscopic treatment compared to the SOC alone. ... 54

3. THE RESEARCH STUDIES ... 56

3.1. Endoscopic treatment of acute variceal hemorrhage by using hemostatic powder TC-325: A prospective pilot study. ... 56

3.2. Management of acute variceal bleeding using Hemostatic powder. ... 58

3.3. Early application of hemostatic powder added to standard management for esophagogastric variceal bleeding. A randomized trial. ... 61

3.4. Active bleeding caused by portal hypertensive gastropathy ... 63

3.5. Novel application of Hemospray to achieve hemostasis in post-variceal banding esophageal ulcers that are actively bleeding ... 64

3.6. New developments in managing variceal bleeding ... 65

4. DISCUSSION, PERSPECTIVES AND RECOMMENDATION ... 67

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