REVIEW Portal hypertension: the management of esophageal/gastric varices, portal hypertensive gastropathy or hypertensive colopathy Giampaolo Bresci Portal hypertension is one of the main consequences of cirrhosis. Esophageal varices are UO Gastroenterologia, AOUPisana, Italy most often a consequence of portal hypertension, although they can also be formed in Tel.: +39 0504 5227; other areas of the body, including the stomach, duodenum, colon and/or rectum. Patients Fax: +39 0504 5227; with esophageal varices have a strong tendency to develop bleeding. Conversely, varices E-mail: [email protected] do not bleed if the hepatic venous pressure gradient is below 12 mmHg. Approximately 30–50% of patients with esophageal varices will bleeding within the first year of diagnosis. Once a patient experiences bleeding, the risk of rebleeding is high, reaching 80% within 1 year. The mortality rate for esophageal variceal bleeding, on the first event, is between 40 and 70%. Endoscopy can be useful in searching for varices with respect to primary prophylaxis and treatment of bleeding in cirrhotics. The treatment of esophageal varices can be pharmacologic, endoscopic or surgical. Three different clinical situations must be distinguished: in primary prophylaxis of esophageal variceal bleeding, the use of β-blocker treatment is only recommended in patients at high risk; in treatment of acute variceal hemorrhage, combining pharmacotherapy for 3–5 days with endoscopic therapy reduces rebleeding compared with either measure alone; in secondary prophylaxis of esophageal variceal bleeding, the treatment of choice is eradication of esophageal varices with band ligation. When the bleeding is refractory, the use of balloon tamponade may stop hemorrhage at least temporarily. If bleeding is uncontrolled, transjugular intrahepatic portosystemic shunt or nonselective portosystemic shunt may be suitable in patients with cirrhosis, provided that the liver dysfunction is not too severe. None of these measures, while being effective in stopping bleeding, have been shown to affect surveillance. Portal hypertension is one of the main conse- are activated as counter-regulatory mecha- quences of cirrhosis. It results from a combina- nisms. Portal venous pressure (P) is the prod- tion of increased intrahepatic vascular uct of vascular resistance (R) and blood flow resistance and increased blood flow through the (Q) in the portal bed (P = Q × R). A normal portal venous system. Major complications of hepatic venous pressure gradient (HVPG) is portal hypertension include the development less than 5 mmHg. A HVPG of 12mmHg is esophageal, gastric or colonic varices. Esopha- necessary, but not sufficient, for varices to geal varices are dilated blood vessels within the form. They form preferentially in the submu- wall of the esophagus. The most common cause cosa of lower esophagus. The lower esophagus of portal hypertension is alcoholic or postviral is a site of portosystemic anastamosis, meaning liver disease. Other etiologies of portal hyper- that venous blood flow in the portal circulation tension include portal vein thrombosis, schisto- (i.e., draining into the portal vein) and the somiasis, and inferior vena caval obstruction by mesenteric circulation mix freely. When portal tumor or thrombus [1–3]. pressures increase, there is dilation of veins in Cirrhosis is the most common cause of por- the anastamosis, leading to esophageal varices. Keywords: esophageal varices, tal hypertension. In cirrhosis, both intrahe- Varices can also be formed in other areas of the gastric varices, gastrointestinal patic vascular resistance and portal flow are body, including the stomach, duodenum, bleeding, hypertensive increased. The hyperdynamic circulation of colon and/or rectum. These blood vessels con- colopathy, portal hypertension, portal cirrhosis results from an imbalance between tinue to dilate until they become large enough hypertensive gastropathy vasoconstrictor and vasodilator mechanisms, to rupture [4]. leading to decreased resistance in the splanch- Patients with esophageal varices have a strong part of nic and systemic circulation. As a consequence, tendency to develop bleeding. Approximately the adrenergic and renin–angiotensin systems 30% of cirrhotic patients have esophageal 10.2217/14750708.4.1.91 © 2007 Future Medicine Ltd ISSN 1475-0708 Therapy (2007) 4(1), 91–96 91 REVIEW – Bresci varices at the time of diagnosis; this proportion recently proposed platelet count:spleen diame- increases with time and reaches 90% after ter ratio appears to be the best noninvasive pre- approximately 10 years. Diagnosis of esopha- dictor of esophageal varices developed to date. geal varices requires endoscopy. Rupture and The platelet count:spleen diameter ratio may bleeding from esophageal varices is a major be proposed as a safe and reproducible means complication of portal hypertension and carries to improve the management of cirrhotic a high mortality. Varices rupture if the wall ten- patients; however, the available evidence is not sion becomes too large. Clinical risk factors for yet sufficient to allow for the modification of an initial bleeding episode include poor liver the current policy of screening cirrhotic function and continuing alcohol consumption. patients by endoscopy [8]. For some years, the Endoscopic predictors of bleeding include the use of wireless capsule endoscope to study the size of the varices and the presence of red color gastrointestinal tract has been proposed but, signs or red wale markings corresponding to only recently, a new video capsule has been pro- areas of thinning of the varix wall owing to high posed specifically to view the inner lining of wall tension. The rupture and bleeding is again the esophagus. The capsule is equipped with proportionate to the HVPG. Conversely, there miniature cameras and the patient swallows the is not bleeding if the HVPG is below capsule lying down, before it travels through 12 mmHg. Approximately 30–50% of patients the esophagus by normal peristaltic waves, cap- with esophageal varices will bleed within a year turing images of the esophagus. The images of diagnosis. Despite advances in intensive care, captured may identify potential abnormalities, bleeding episodes still carry a high mortality, such as esophagitis, esophageal ulcers and also which mainly depends on the severity of the esophageal varices. This new capsule endoscopy underlying liver disease. Once a patient has is safe, highly acceptable and preferred by bleeding, the risk of rebleeding is high, reaching patients, although it may prove to be more 80% within 1 year [5]. cost-effective than conventional endoscopy [9]. The mortality of any bleeding episode may Propranolol was shown to reduce the inci- range from 10% or less in well compensated dence of variceal bleeding in patients who had Child–Pugh A to 70% or over in advanced no previous bleeding, therefore cirrhotics who Child–Pugh C cirrhotics, respectively. The mor- have varices, regardless of their size, should tality rate for esophageal variceal bleeding, on the receive primary prophylaxis with nonselective first event, is between 40 and 70%. The treat- β-blockers. The aim of pharmacotherapy is to ment of esophageal varices can be pharmacologi- reduce HVPG and, thus, collateral blood flow cal, endoscopic or surgical and three different and pressure through/in the varices. Reducing clinical situations must be distinguished [6]: portal pressure by 20% from baseline reduces • Primary prophylaxis of esophageal variceal the risk of rebleeding from over 60% to less bleeding (prevention of a first variceal bleed) than 10% at 3 years; if HVPG is lowered below 12 mmHg there is no bleeding. Nonselective • Treatment of acute variceal hemorrhage β-blockers reduce cardiac output, splanchnic • Secondary prophylaxis of esophageal variceal arterial inflow, portal venous flow and pressure bleeding (prevention of rebleeding) and, thus, variceal flow and pressure. In cirrhot- ics with esophageal varices, both propranolol Primary prophylaxis of esophageal and nadolol have been demonstrated to reduce variceal bleeding (prevention of a first the risk of an initial bleeding episode by variceal bleed) 40–50%, while there was a trend only in reduc- Any patients with portal pressure greater than ing mortality. Approximately 30% of patients 12 mmHg is at risk of esophageal varices, thus will not respond to nonselective β-blockers they should be screened edoscopically for the with a reduction in HVPG, despite adequate presence of varices and, if varices are present, dosing. These nonresponders can only be measures should be taken to reduce the change detected by invasive measurements of HPVG. of hemorrhage [7]. Upper gastrointestinal Bleeding may occur when nonselective β-block- endoscopy is usually recommended for the ers are abruptly discontinued, thus this therapy evaluation of esophageal varices in patients should be lifelong if tolerated. Nonselective β- with liver cirrhosis. The possibility of identify- blockers may cause side effects, such as brady- ing cirrhotic patients with esophageal varices cardia, brocospasm, hypoglycemia, fatigue and by noninvasive means is attractive and the impotence [10,11]. 92 Therapy (2007) 4(1) futurefuture sciencescience groupgroup Portal hypertension – REVIEW The addition of isosorbide mononitrate to however, the patients have gone in hospital. Ini- nonselective β-blockers has been evaluated. Iso- tial measures are directed at general resuscitation sorbide 5-mononitrate has