Drugs 2008; 68 (16): 2303-2324

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2303 1. Pathophysiology of Portal Hypertension and Variceal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2305 2. Evaluation of Portal Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2305 3. Effects of Pharmacological Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2306 3.1 Vasoconstrictors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2307 3.1.1 Vasopressin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2307 3.1.2 Terlipressin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2307 3.1.3 Somatostatin and its Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2307 3.1.4 Nonselective β-Adrenoceptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2307 3.2 Vasodilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2308 3.3 Combined Drug Therapy with Vasoconstrictors and Vasodilators . . . . . . . . . . . . . . . . . . . . . . . . 2309 4. Haemodynamic Monitoring of Pharmacological Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2310 5. Pharmacological Therapy in Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2311 5.1 Treatment of Acute Variceal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2311 5.1.1 General Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2311 5.1.2 Haemostatic Treatment of Acute Variceal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2312 5.1.3 Management of Therapeutic Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2313 5.2 Treatment to Prevent Rebleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2313 5.2.1 First-Line Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2313 5.2.2 Management of Therapeutic Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2314 5.3 Treatment to Prevent the First Variceal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2316 5.4 Gastric Varices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2318 5.5 Portal Hypertensive Gastropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2319 6. Recommendations in Special Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2319 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2320 Oesophageal varices and ascites may develop when the hepatic venous presAbstract sure gradient (HVPG) increases above 10 mmHg, and variceal bleeding may occur when the HVPG rises above 12 mmHg. Pharmacological therapy of portal hypertension may prevent bleeding by reducing the HVPG below 12 mmHg. Even if this threshold level is not reached, the risk of bleeding decreases markedly with reductions in HVPG that are >20% from baseline. Endoscopic therapy is a local treatment that prevents bleeding by obliterating the varices, and has no effect on the pathophysiological mechanisms that lead to 2304 Villanueva & Balanzó portal hypertension and variceal rupture. When used together, both pharmacological and endoscopic therapies may have an additive effect, which has been demonstrated in different clinical settings. In acute oesophageal variceal bleeding, vasoactive drugs (either terlipressin or somatostatin) should be started as soon as possible (before diagnostic endoscopy) and maintained for 2–5 days. The efficacy of pharmacotherapy is improved with the addition of emergency endoscopic therapy. Adding endoscopic variceal ligation (EVL) improves the efficacy and safety achieved with the combination of emergency sclerotherapy and vasoactive drugs. Antibacterial prophylaxis should be an integral part of therapy in acute