Clinical review

Portal hypertension1: varices

J E J Krige, I J Beckingham. 

The portal vein carries about 1500 ml/min of blood from the small and large bowel, spleen, and stomach to the liver at a pressure of 5-10 mm Hg. Any obstruction or increased resistance to flow or, rarely, pathological increases in portal blood flow may lead to portal hypertension with portal pressures over 12 mm Hg. Although the differential diagnosis is extensive, alcoholic and viral cirrhosis are the leading causes of portal hypertension in Western countries, whereas liver disease due to schistosomiasis is the main cause in other areas of the world. Portal vein thrombosis is the commonest cause in children.

View larger version (32K): [in this window] [in a new window]   Anatomical relations of portal vein and branches

Increases in portal pressure cause development of a portosystemic collateral circulation with resultant compensatory portosystemic shunting and disturbed intrahepatic circulation. These factors are partly responsible for the important complications of chronic liver disease, including variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome, recurrent infection, and abnormalities in coagulation. Variceal bleeding is the most serious complication and is an important cause of death in patients with cirrhotic liver disease.

	Varices

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In Western countries variceal bleeding accounts for about 7% of episodes of gastrointestinal bleeding, although this varies according to the prevalence of alcohol related liver disease (11% in the United States, 5% in the United Kingdom). Patients with varices have a 30% lifetime risk of bleeding, and a third of those who bleed will die. Patients who have bled once from oesophageal varices have a 70% chance of bleeding again, and about a third of further bleeding episodes are fatal.

Several important considerations influence choice of treatment and prognosis. These include the natural course of the disease causing portal hypertension, location of the bleeding varices, residual hepatic function, presence of associated systemic disease, continuing drug or alcohol misuse, and response to specific treatment. The modified Child-Pugh classification identifies three risk categories that correlate well with survival.

Initial measures
Prompt resuscitation and restoration of circulating blood volume is vital and should precede any diagnostic studies. While their blood is being cross matched, patients should receive a rapid infusion of 5% dextrose and colloid solution until blood pressure is restored and urine output is adequate. Saline infusions may aggravate ascites and must be avoided. Patients who are haemodynamically unstable, elderly, or have concomitant cardiac or pulmonary disease should be monitored by using a pulmonary artery catheter as injudicious administration of crystalloids, combined with vasoactive drugs, can lead to the rapid onset of oedema, ascites, and hyponatraemia. Concentrations of clotting factors are often low, and fresh blood, fresh frozen plasma, and vitamin K₁ (phytomenadione) should be given. Platelet transfusions may be necessary. Sedatives should be avoided, although haloperidol is useful in patients with symptoms of alcohol withdrawal.

Pharmacological control
Drug treatment, aimed at controlling the acute bleed and facilitating diagnostic endoscopy and emergency sclerotherapy, may be useful when variceal bleeding is rapid. Octreotide, a synthetic somatostatin analogue, reduces splanchnic blood flow when given intravenously as a constant infusion (50 µg/h) and can be used before endoscopy in patients with active bleeding. Vasopressin (0.4 units/min), or the long acting synthetic analogue terlipressin, combined with glyceryl trinitrate administered intravenously or transdermally through a skin patch is also effective but has more side effects than octreotide. Glyceryl trinitrate reduces the peripheral vasoconstriction caused by vasopressin and has an additive effect in lowering portal pressure.

View larger version (35K): [in this window] [in a new window]   Algorithm for management of acute variceal haemorrhage

	Emergency endoscopy

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Emergency diagnostic fibreoptic endoscopy is essential to confirm that oesophageal varices are present and are the source of bleeding. Most patients will have stopped bleeding spontaneously before endoscopy (60% of bleeds) or after drug treatment. Endotracheal intubation may be necessary during endoscopy, especially in patients who are bleeding heavily, encephalopathic, or unstable despite vigorous resuscitation. In 90% of patients variceal bleeding originates from oesophageal varices. These are treated by injection with sclerosant or by banding.

View larger version (259K): [in this window] [in a new window]   Injection of varices with sclerosant

Sclerotherapy
In sclerotherapy a sclerosant solution (ethanolamine oleate or sodium tetradecyl sulphate) is injected into the bleeding varix or the overlying submucosa. Injection into the varix obliterates the lumen by thrombosis whereas injection into the submucosa produces inflammation followed by fibrosis. The first injection controls bleeding in 80% of cases. If bleeding recurs, the injection is repeated. Complications are related to toxicity of the sclerosant and include transient fever, dysphagia and chest pain, ulceration, stricture, and (rarely) perforation.

Band ligation
Band ligation is achieved by a banding device attached to the tip of the endoscope. The varix is aspirated into the banding chamber, and a trip wire dislodges a rubber band carried on the banding chamber, ligating the entrapped varix. One to three bands are applied to each varix, resulting in thrombosis. Band ligation eradicates oesophageal varices with fewer treatment sessions and complications than sclerotherapy.

Balloon tube tamponade
The balloon tube tamponade may be life saving in patients with active variceal bleeding if emergency sclerotherapy or banding is unavailable or not technically possible because visibility is obscured. In patients with active bleeding, an endotracheal tube should be inserted to protect the airway before attempting to place the oesophageal balloon tube.

View larger version (67K): [in this window] [in a new window]   Band ligation of oesophageal varix

	Alternative management

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Transjugular intrahepatic portosystemic shunt
Transjugular intrahepatic portosystemic shunt is the best procedure for patients whose bleeding is not controlled by endoscopy. It is effective only in portal hypertension of hepatic origin. The procedure is performed via the internal jugular vein under local anaesthesia with sedation. The hepatic vein is cannulated and a tract created through the liver parenchyma from the hepatic to the portal vein, with a needle under ultrasonographic and fluoroscopic guidance. The tract is dilated and an expandable metal stent inserted to create an intrahepatic portosystemic shunt. The success rate is excellent. Haemodynamic effects are similar to those found with surgical shunts, with a lower procedural morbidity and mortality.

View larger version (22K): [in this window] [in a new window]   Minnesota balloon for tamponade of oesophageal varices

View larger version (37K): [in this window] [in a new window]   Transjugular intrahepatic portosystemic shunt

	Long term management

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After the acute variceal haemorrhage has been controlled, treatment should be initiated to prevent rebleeding, which occurs in most patients.

Repeated endoscopic treatment
Repeated endoscopic treatment eradicates oesophageal varices in most patients, and provided that follow up is adequate serious recurrent variceal bleeding is uncommon. Because the underlying portal hypertension persists, patients remain at risk of developing recurrent varices and therefore require lifelong regular surveillance endoscopy.

Long term drug treatment
The use of  blockers after variceal bleeding has been shown to reduce portal blood pressures and lower the risk of further variceal bleeding. All patients should take  blockers unless they have contraindications. Best results are obtained when portal blood pressure is reduced by more than 20% of baseline or to below 12 mm Hg.

View larger version (38K): [in this window] [in a new window]   Surgical management of varices

Surgical procedures
Patients with good liver function in whom endoscopic management fails or who live far from centres where endoscopic sclerotherapy services are available are candidates for surgical shunt procedures. A successful portosystemic shunt prevents recurrent variceal bleeding but is a major operation that may cause further impairment of liver function. Partial portacaval shunts with 8 mm interposition grafts are equally effective to other shunts in preventing rebleeding and have a low rate of encephalopathy.

	Prophylactic management

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Most patients with portal hypertension never bleed, and it is difficult to predict who will. Attempts at identifying patients at high risk of variceal haemorrhage by measuring the size or appearance of varices have been largely unsuccessful.  blockers have been shown to reduce the risk of bleeding, and all patients with varices should take them unless contraindicated.

	Gastric varices and portal hypertensive gastropathy

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Gastric varices are the source of bleeding in 5-10% of patients with variceal haemorrhage. Higher rates are reported in patients with left sided portal hypertension due to thrombosis of the splenic vein. Endoscopic control of gastric varices is difficult unless they are located on the proximal lesser curve in continuation with oesophageal varices. Endoscopic administration of cyanoacrylate monomer (superglue) is useful for gastric varices. The transjugular intrahepatic portosystemic shunt is increasingly used to control bleeding in this group.

View larger version (145K): [in this window] [in a new window]   Hypertensive portal gastropathy

Bleeding from portal hypertensive gastropathy accounts for 2-3% of bleeding episodes in cirrhosis. Although serious bleeding from these sources is uncommon, when it occurs its diffuse nature precludes the use of endoscopic treatment, and optimal management is with a combination of terlipressin and  blockers.

	Footnotes

J E J Krige is associate professor of surgery, Groote Schuur Hospital and University of Cape Town, South Africa.

The ABC of diseases of liver, pancreas, and biliary system is edited by I J Beckingham, consultant hepatobiliary and laparoscopic surgeon, department of surgery, Queen's Medical Centre, Nottingham (Ian.Beckingham{at}nottingham.ac.uk). The series will be published as a book later this year.