Portal Hypertension

Portal hypertension refers to abnormally high pressure in the hepatic portal vein. It is defined as a portal pressure of 12 mmHg or more compared with a normal figure of 5 to 10 mmHg.¹ Alternatively, it can be defined by the gradient between the wedged (occluded) hepatic venous pressure and the free hepatic venous pressure; the normal gradient is < 5 mmHg.²

There are related articles on: Cirrhosis, Liver Failure, Oesophageal Varices, Ascites and Hepatorenal Syndrome.

Causes can be divided into: prehepatic, hepatic and posthepatic. Cirrhosis is a common cause.

Pathophysiology^1,2

The raised portal pressure opens up venous collaterals, connecting the portal and systemic venous systems. These collaterals occur in various sites: the most clinically relevant are gastro-oesophageal junction (producing varices which can bleed as they are superficial) and on the anterior abdominal wall via the umbilical vein (visible as caput medusae radiating from the umbilicus).

There is a release of mediators, leading to a hyperdynamic circulation with salt and water retention. In combination with portal hypertension, this causes ascites. With ascites, renal perfusion and renal function may be affected: this is hepatorenal syndrome.

The porto-systemic venous anastomoses can cause encephalopathy: the mechanism of this is uncertain, but may be due to various 'toxins' bypassing the liver's 'detoxification' process.

Portal hypertension itself does not produce symptoms, so patients usually present either with symptoms of liver disease, or with complications of portal hypertension such as bleeding varices.

History

For causes of liver disease:

• History of jaundice.
• Alcohol consumption.
• Blood transfusion, especially abroad.
• Sexual or drug taking lifestyle that may predispose to hepatitis B or hepatitis C.
• Family history of liver disease such as Wilson's disease or hereditary haemochromatosis.

For complications of portal hypertension:

• Haematemesis or melena are features of upper gastrointestinal bleeding and suggest bleeding varices.
• Mental changes including lethargy, irritability and changes in sleep pattern suggest encephalopathy.
• Increased abdominal girth and rapid weight gain suggests ascites.
• Abdominal pain and fever suggest spontaneous bacterial peritonitis.

Examination¹

Signs of portal hypertension

• Dilated veins in the anterior abdominal wall and caput medusae (tortuous collaterals around the umbilicus). A venous hum, loudest during inspiration, is sometimes heard over large upper abdominal collaterals.
• Splenomegaly.
• Ascites.

Signs of liver disease

• Jaundice, spider naevi, palmar erythema.
• Confusion, liver flap and foetor hepaticus are signs of encephalopathy.
• Signs of hyperdynamic circulation: bounding pulse, low blood pressure, warm peripheries.
• Enlarged or small liver.
• Gynaecomastia and testicular atrophy.

• Blood tests:
  • Liver function, urea & electrolytes, glucose, full blood count, clotting screen.
  • Investigations for liver disease if cause not known, e.g: ferritin (for haemochromatosis), hepatitis serology, autoantibodies, alpha-1-antitrypsin (for alpha-1-antitrypsin deficiency), ceruloplasmin (for Wilson's disease).
• Scans:
  • Abdominal ultrasound can show ascites, portal blood flow and thrombosis of the portal or splenic veins. It shows the size of the liver and any irregularities. It may also demonstrate splenomegaly.
  • Doppler ultrasound can show the direction of flow in individual vessels, and allows quantitation in major vessels.
  • CT, especially spiral CT, may show portal vasculature and be useful if ultrasound was inconclusive. MRI gives similar information.
• Endoscopy:
  • Patients with cirrhosis or suspected portal hypertension need endoscopy to assess/treat oesophageal varices (see management and complications section). Varices indicate portal hypertension but their absence does not exclude it.
• Invasive tests:
  • The site of the block can be demonstrated by examining the venous phase of a coeliac or superior mesenteric arteriogram, by splenic portography following injection of dye into the splenic pulp, or by retrograde portography via a hepatic vein.
  • Hepatic venography is helpful when hepatic-vein block or idiopathic portal hypertension are suspected.
  • Portal hypertension can be confirmed by wedged hepatic venous pressure (i.e. by a catheter in the hepatic venous system). Direct measurement of portal pressure, by splenic puncture or transhepatic cannulation of a portal vein branch is rarely needed.
  • Liver biopsy may be performed if coagulation studies are satisfactory; may indicate the cause of liver disease or portal hypertension.

• Treat the specific cause, where possible.
• Liver transplant: depending on the underlying disease, this may be the ideal treatment, as it will cure both the portal hypertension and the liver problem. It is limited by donor availability, and not all cases are suitable for transplantation.
• Management of complications - see below.

Types of treatment for portal hypertension²

• Low salt diet.
• Diuretics for ascites: spironolactone is first-line to counteract sodium retention; loop diuretics may be added.
• Beta blockers (non-selective) reduce portal venous pressure, but some patients may be 'non-responders' to this treatment.
• Vasoactive drugs - reduce hepatic venous pressure gradient :
  • Somatostatin or its analogues octreotide and vapreotide.
  • Vasopressin or terlipressin - splanchnic vasoconstrictors but have ischaemic side-effects.
• Portosystemic shunt procedures:
  • TIPS (transjugular intrahepatic portosystemic shunt)⁴ - a radiological procedure, not requiring anaesthetic, connects the portal and hepatic veins. This reduces portal pressure, but the drawbacks are a higher risk of encephalopathy and a high rate of stenosis requiring re-intervention.
  • Portosystemic surgical shunt: requires major surgery and experienced surgeon; less likely to stenose than TIPS and can be used where TIPS not feasible.

Gastro-oesphageal varices^2,5

See separate article on Oesophageal Varices.

Primary prevention of variceal bleeding

Screen all patients with cirrhosis by endoscopy at 3-yearly intervals (2-yearly if small varices are found). Primary prevention should be given for:

• Large or medium-sized varices
• Small varices with 'red signs'
• Small varices in patients at high risk (class B-C in Child-Pugh classification - see table below):

Treat with:

• Nonselective β-blockers, e.g. propranolol, nadolol - these reduce portal pressure and complications. Adjust the dose to achieve a 20-25% reduction in heart rate or a rate <55 beats/min.
• If β-blockers contra-indicated or not tolerated, endoscopic band ligation of varices.

Acute variceal bleeding

This is a life-threatening emergency. For management see related oesophageal varices article. Also, other sources of bleeding such as epistaxis can mimic variceal bleeding in patients with liver disease.⁶

Secondary prevention after variceal bleeding⁵

• Beta blockers as above
• Endoscopic band ligation (EBL) of varices followed by endoscopic surveillance (initially 1-3 monthly, then 6-12 monthly)
• Consider TIPS
• Consider liver transplant

Rectal varices

These are the lower G-I counterpart of oesophageal varices but are less likely to bleed. They are common in patients with portal hypertension; they are located at the anorectal junction and are not the same as haemorrhoids. If they bleed, suggested treatment is similar to the that used for upper G-I varices, i.e. using drugs to reduce portal pressure, endoscopic banding and TIPS if bleeding persists.⁷ Varices may also form at the site of a stoma and they too may bleed.⁸

Ascites^2,9

See also the separate article on Ascites. As a summary, management involves:

• Paracentesis, looking for spontaneous bacterial peritonitis (see below).
• Low sodium diet (<90 mmol/day).
• Diuretics: usually spironolactone ± loop diuretic. High doses may be needed in severe ascites.
  Careful monitoring is needed to avoid over-diuresis and dehydration which worsens renal function.
• Severe ascites may require paracentesis; with large volume paracentesis (>4-5 litres) consider volume expansion using albumin infusion.
• Refractory ascites: TIPS (if suitable) and liver transplant.

Spontaneous bacterial peritonitis

This is serious and common complication of ascites.

• All patients with ascites should have diagnostic paracentesis to screen for bacterial peritonitis. Repeat the test if there is clinical deterioration such as worsening encephalopathy. Remember that symptoms such as abdominal pain or fever may be absent. Treatment helps prevent hepatorenal syndrome (below) and death.
• Treat if ascitic fluid has neutrophils >250/mm³ or if symptoms/signs of bacterial peritonitis. (Reagent sticks for leucocytes may also be useful).
  • Antibiotics: 3rd generation cephalosporin, co-amoxiclav or norfloxacin.
  • Albumin infusion should be given.

Prophylaxis: secondary prophylaxis is recommended after an episode of spontaneous bacterial peritonitis (e.g. norfloxacin). Primary prophylaxis for patients with ascites is controversial.

Hepatorenal syndrome^2,10

See separate article on Hepatorenal Syndrome.This is a serious complication of ascites with cirrhosis and portal hypertension. It is due to the complex changes in circulation and fluid balance occurring in this context, which lead to renal vasoconstriction and hypoperfusion. There are 2 forms of this syndrome known as type I and type II.

• Prevention:
  • Albumin infusion and antibiotics for patients with spontaneous bacterial peritonitis.
  • Possibly, oral pentoxifylline in patients with acute alcoholic hepatitis.¹⁰
• Possible treatments are:
  • Albumin.
  • Vasoactive drugs such as terlipressin, octreotide, midodrine or noradrenaline may help.
  • TIPS improves renal function.
  • Haemodialysis if required.
  • Liver transplant is the best treatment.

Portosystemic encephalopathy¹¹

This is a neuropsychiatric syndrome due to reduced hepatocellular function and increased portosystemic shunting. The terms hepatic encephalopathy and portosystemic encephalopathy are usually used interchangeably. However, the term portosystemic encephalopathy may be more appropriate for encephalopathy complicating increased portosystemic shunting in the absence of overt hepatocellular failure.

Hepatic encephalopathy can be acute, chronic or episodic. If acute, there is usually a precipitating factor.

The article on Liver Failure details the grading, precipitating factors and treatment of hepatic encephalopathy. Treatment involves:

• Treat precipitating factors e.g. G-I bleeding, bacterial peritonitis, constipation
• Optimising nutrition
• Lactulose ± antibiotics
• Consider closure or narrowing of portosystemic shunts e.g. a TIPS
• Intensive care is often required¹²
• May need liver transplant
• Flumazenil may have a role¹³

This depends on the prognosis of the underlying disease, and on the outcome of any complications such as variceal bleeding.

The Child-Pugh classification system¹⁴ indicates prognosis in some types of liver disease such as cirrhosis. "MELD" is an alternative score, but the Child-Pugh system remains valid.¹⁵