The term portal hypertension was first mentioned in 1906 by Gilbert and Vilaret, when the association between cirrhosis, ascites and gastrointestinal haemorrhage was described. The normal pressure of the portal venous system is 5–10 mm Hg and maintains the liver blood flow at approximately 1 L/min. Portal hypertension is defined as portal venous pressures greater than 10 mm Hg.
The portal venous circulation is one of three venous systems in the human which is formed and terminates in a capillary system. It provides approximately 60% to 80% of total hepatic blood flow. The portal vein is formed by the confluence of the splenic and superior mesenteric vein behind the neck of the pancreas. The superior mesenteric vein is formed by venous tributaries from the jejunum, ileum and colon, the predominant being middle, right and iliocolic veins. The left gastric vein (coronary vein) and the right gastric vein drain into the main portal vein close to its origin while the right gastroepiploic vein drains into the superior mesenteric vein near its termination. The left gastroepiploic and inferior mesenteric veins enter the portal system in the vicinity of the splenic and portal vein junction. There are no valves in the portal venous system. This allows an increase in portal venous pressure to be equally distributed across the entire system, including potential collateral sites.
Portal hypertension may be caused by increased blood flow into the portal venous system or by portal venous outflow obstruction.
Increased portal blood flow is an uncommon cause of portal hypertension. This is usually caused by arteriovenous fistulas, which may occur secondary to trauma, arteriovenous malformations or tumours. Massive splenomegaly secondary to myeloproliferative disorders is a rare cause of portal hypertension where the hyperdynamic splenic blood flow results in increased portal venous pressure.
Obstruction to the portal circulation is by far the most common cause of portal hypertension. It is further classified on the basis of the anatomical site of obstruction as pre-sinusoidal, sinusoidal or post-sinusoidal portal hypertension
Pre-sinusoidal obstruction accounts for 10–15% of cases of portal hypertension and may occur in the intra- or extra-hepatic parts of the portal system. These include splenic and portal vein thrombosis. Rarely, congenital absence or abnormality of the portal vein may also be a cause. Portal vein thrombosis in the child is predominantly related to umbilical sepsis. In the adult, hypercoagulable states such as polcythaemia rubra vera or myeloproliferative disorders are the major causes of portal vein thrombosis. Isolated splenic vein thrombosis may occur secondary to tumours of the pancreas or pancreatitis. Intrahepatic causes of pre-sinusoidal portal hypertension include schistosomiasis, congenital hepatic fibrosis and other rarer causes such as primary portal hypertension and infiltration by sarcoidosis and reticulosis.
Post-sinusoidal obstruction accounts for approximately 2–5% of patients with portal hypertension and is mainly caused by veno-occlusive disease or Budd-Chiari Syndrome. Veno-occlusive disease occurs in the sublobular branches of the hepatic veins. Factors causing this condition include antineoplastic drugs and irradiation. Other causes of post-sinusoidal obstruction are Budd-Chiari Syndrome and constrictive pericarditis. The Budd-Chiari syndrome may be caused by hepatic vein stenosis and membranous webs of the hepatic veins. The most common cause of this syndrome is thrombosis caused by hypercoagulable states or myeloproliferative conditions majority of cases of portal hypertension. Alcohol ingestion and viral infection (Hepatitis B and C) are the major causes of cirrhosis. Other causes include primary biliary cirrhosis, schlerosing cholangitis, autoimmune disorders, Wilson's disease and other enzyme deficiencies. The major implication in this group of patients with portal hypertension is the underlying presence of hepatocellular damage. This has both prognostic and management implications.
The main consequence of raised portal venous pressure (>10 mm Hg and usually >20 mm Hg) is the development of collaterals with the systemic circulation at multiple sites. The most common sites include the oesophagogastric junction (oesophageal varices), peri-umbilical area (caput medusae), superior haemorrhoidal veins (haemorrhoids) and retroperitoneal collaterals. These anastomotic channels progressively become engorged, leading to increased blood flow and gradual dilatation. The major sequelae of portal hypertension are gastrointestinal haemorrhage, the development of ascites, chronic porta-systemic encephalopathy and hypersplenism secondary to splenomegaly.
Fine anastomoses develop between the systemic and portal circulation in the submucous plexus of the oesophagus and stomach. Eventually the submucosa disappears and the wall of the veins becomes the lining of the oesophagus. Rupture of these vessels cause significant bleeding. The two most important factors contributing to bleeding varices are the underlying increase in portal venous pressure and ulceration secondary to oesophagitis. Patients with cirrhosis have a higher incidence of variceal bleeding in contrast to other noncirrhotic causes of portal hypertension. The incidence of varices is also related to the severity of the underlying liver disease. Bleeding from ruptured oesophagogastric varices is the most severe complication of cirrhosis and is the cause of death in about one third of these patients.
A reduction in the colloidal osmotic pressure related to hypoalbuminaemia, sodium and water retention caused by abnormal hormonal and circulating vasoactive agents and vasodilation of the splanchnic circulation ultimately lead to the formation of ascites. The development and severity is often aggravated by surgery, systemic infection, gastrointestinal bleeding and hepatic decompensation. Spontaneous bacterial peritonitis may complicate pre-existing ascites.
This frequently accompanies portal hypertension. It is characterised by anaemia, thrombocytopenia and leukopenia.
Neuropsychiatric symptoms commonly develop in patients with portal hypertension and underlying hepatocellular dysfunction. Encephalopathy is related to impaired ammonia metabolism caused by extensive collaterals which bypass the liver and by the underlying hepatocellular dysfunction. The early stages are characterised by mental confusion and delirium, followed by stupor and coma. It is a prominent feature in patients with bleeding varices, as this leads to increased production of nitrogen compounds within the gastrointestinal tract.
Classification of the severity of the underlying liver disease in a patient with portal hypertension is important from a prognostic and management point of view. The Child-Pugh classification (see Table 23, “Child-Pugh classification of severity of liver disease”) is the most commonly used grading to assess the severity of underlying liver disease.
|Prothrombin time (sec)||<4||4–6||>6|
|Bilirubin level (mg/dL)||<2(<4)||2–3(4–10)||>3(>10)|
|(In cholestatic disease)|
The major clinical differentiation in patients with portal hypertension is the presence of underlying chronic hepatocellular liver disease and the detection of complications.
A history of liver disease, cirrhosis and gastrointestinal bleeding should be specifically requested. Detailed information relating to the aetiology of the liver disease should be sought. This should include the duration and extent of alcohol intake, previous episodes of jaundice and hepatitis, previous blood transfusions and any risky behaviour for the transmission of bloodborne diseases. A family history of liver disease may provide clues to genetic causes of liver disease. Routine medications which the patient may be on, especially oral contraceptives, and particularly of recent onset, should be listed.
Previous upper or lower gastrointestinal bleeding should be documented, including frequency and severity of episodes. Any associated symptoms of ascites or encephalopathy should be noted as well as a history of umbilical sepsis, pancreatitis or coexistent malignancy.
This should aim to elucidate features of the underlying chronic liver disease, signs specific to the aetiology of the disease and the presence of portal hypertension. Apart from the common signs of chronic liver disease such as gynaecomastia, testicular atrophy spider naevi, the presence of bilateral parotid enlargement, Dupytren's contractures and Keiser-Fleischer rings may provide a clue to the aetiology of the disease. Splenomegaly, ascites, caput medusae and abdominal wall collaterals are specifically indicative of portal hypertension. A venous hum may be present in the periumbilical area.
The presence of chronic liver disease and clinical evidence of portal hypertension should lead to investigations tailored to the identification of the underlying disease, the severity of the disease and identification of potential complications.
Full blood examination
A low haemoglobin or decreased hematocrit may indicate either continued bleeding or anaemia of chronic liver disease. Thrombocytopenia or low white cell count may indicate hypersplenism. A coagulation profile is essential for the management and for prognostic contribution to the Child-Pugh system. An elevated prothrombin time or International Normalised Ratio (INR) is a strong indicator of synthetic dysfunction and indicates severe hepatocellular disease. Plasma fibrinogen may also be a useful indicator to the risk of bleeding.
Renal function tests
Electrolyte imbalance, especially low sodium levels, may occur in patients with chronic liver disease. The urea and creatinine levels may not only be an indicator of renal dysfunction but may also be a useful indirect guide to liver function.
Serum bilirubin is important in assessing liver function as well as contributing to the Child-Pugh score. Albumin levels may indicate underlying synthetic function, the degree of malnutrition and also contribute to prognostic evaluation. Alkaline phosphatase and gamma gluteryl transferase reflect underlying cholestasis. Increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are an indication of acute hepatocellular damage.
The main role of serology is in the diagnosis and assessment of viral hepatitis as the underlying cause. Viral antigen and antibody levels should be investigated as appropriate for Hepatitis A, B and C as well as cytomegalovirus (CMV) and human immunodeficiency virus. Quantitation of viral DNA and RNA levels by more sophisticated techniques allow assessment of viral load and replication. Antimitochondrial antibodies, antinuclear antibodies, alpha-1-antitrypsin levels and genetic testing for Wilson's disease may provide clues to the underlying aetiology of the liver disease.
Abdominal ultrasound should always be performed as an initial screening test to assess liver parenchyma in terms of the degree of cirrhosis, possible space occupying lesions, enlarged lymph nodes or incidental gallstones. A Doppler ultrasound of the portal vein, splenic and superior mesenteric vein, hepatic artery and hepatic veins assesses patency, and the direction and volume of blood flow. Multiphasic CT 1 scans and MRI scans of the abdomen may also be required to delineate specific aspects of liver anatomy. MR angiography and CT angiography have evolved in sophistication to the point where percutaneous invasive angiography has been made redundant. Angiography and venography are used on specific occasions to define certain aspects of the portal circulation and hepatic venous anatomy especially prior to surgery or other interventional techniques. Occluded hepatic vein wedge pressure is the most accurate indirect objective measurement of the portal venous pressure and is performed via percutaneous internal jugular vein catheterisation.
Occluded hepatic vein wedge pressure is the most accurate indirect objective measurement of the portal venous pressure and is performed via percutaneous internal jugular vein catheterisation.
An upper gastrointestinal endoscopy should always be performed in any patient with suspected portal hypertension, in order to define the extent, size and characteristics of oesophageal varices (see Oesophageal varices with ulceration of the mucosa.), as well as any evidence of gastric varices and portal hypertensive gastropathy. It also allows the prophylactic treatment of oesophageal varices, as well as excluding other causes of gastrointestinal haemorrhage such as malignancy and peptic ulcer disease.
This is performed if the nature and severity of the underlying liver disease is unknown. It may be performed percutaneously under ultrasound guidance or by the internal jugular vein to minimise complications of haemorrhage.
The management of the patient with portal hypertension involves the assessment and treatment of any underlying liver disease as well as specific attention to the complications of bleeding, ascites and encephalopathy.
Acute variceal bleeding requires a multidisciplinary approach, including surgeons, gastroenterologists, radiologists and intensive care personnel. The management of variceal bleeding involves initial aggressive resuscitation, early diagnosis, measures to control the acute bleeding and strategies to prevent re-bleeding.
The first priority in the management of patient with acute variceal bleeding is active resuscitation. Intravenous access, including multiple wide-bore peripheral venous cannulae and central venous access, should be established immediately. ASwan-Ganz catheter may be required in the severely comprised patient. A urinary catheter should be inserted to monitor urine output. Blood is withdrawn for grouping and cross-matching. Tests including full blood examination, liver and renal biochemistry and a coagulation profile are performed. Resuscitation usually requires the infusion of large volumes of blood and crystalloid. Most patients will require correction of coagulation defects using platelets, coagulation factors and vitamin K. The gastrointestinal tract should be cleared using cathartics such as lactulose. Non-absorbable antibiotics may be used to achieve selective gut sterilisation. Systemic antibiotics are administered as these patients are susceptible to infection. The aim of resuscitation is to achieve cardiovascular stability with a view to urgent endoscopy.
An urgent endoscopy within 6 hours should be done to confirm the cause and site of bleeding. Repeat endoscopy may be required to achieve this.
Control of bleeding
The initial control of acute variceal bleeding can be achieved in 90–95% of patients by endoscopic sclerotherapy or banding. Endoscopic sclerotherapy involves the injection of one of several agents directly into the varix, leading to thrombosis and fibrosis. Banding of varices is achieved by applying a rubber band to strangulate the varix under endoscopy. It is superior to sclerotherapy in achieving haemostasis and has fewer side effects.
Balloon tamponade of the varices using a Sengstaken-Blakemore tube may be indicated on rare occasions when sclerotherapy and banding fail. This is required in less than 5% of patients and is usually used as a temporising measure to stabilise the patient prior to further attempts at banding or sclerotherapy. The tube is inserted endoscopically and has both gastric and oesophageal balloons, inflated to specific pressures for a limited period, since potentially lethal complications of asphyxia and oesophageal perforation may occur.
Apart from locally applied techniques, variceal bleeding may be decreased temporarily by lowering the underlying portal venous pressure using pharmacological agents, such as continuous infusions of octreotide (a synthetic analogue of somatostatin) or terlipressin, which lower portal pressure and are beneficial in preventing early recurrence of variceal bleeding.
Placing of transjugular intrahepatic portal systemic shunts (TIPS) may be performed under local anaesthetic via percutaneous access of the right internal jugular vein. An internal stent is placed through the liver parenchyma between the right or middle hepatic vein and a branch of the portal vein, creating in essence a side-to-side porta-systemic shunt. Major complications are rare but may include haemorrhage or the development of encephalopathy.
Surgical Procedures are now seldom required for variceal bleeding and are used only when other measures fail. These procedures include local devascularisation procedures and porta-systemic shunts. The local devascularisation procedures include components of splenectomy or splenic artery ligation, oesophageal transection and devascularisation of the oesophagus and stomach by ligation of appropriate vessels. There is a high incidence of re-bleeding with these procedures.
Porta-systemic shunts create an artificial or surgical communication between the portal and systemic venous systems and lower portal pressures. These procedures include portacaval and mesocaval shunts and more selective techniques such as the lieno-renal shunts. These shunts have a significant mortality and morbidity and may be complicated by ascites and encephalopathy.
Prevention of recurrent bleeding
Once the initial bleeding has ceased, measures are instigated to prevent recurrence. These include prophylactic banding or sclerotherapy and the use of pharmacological agents such as oral β-blockers. If patients re-bleed during the primary therapy TIPS may be also be used in the acute setting. Liver transplantation is the procedure of choice to prevent recurrent variceal bleeding in selected patients with cirrhosis, once control of the acute haemorrhage has been achieved. It not only lowers portal venous pressures, but also corrects the underlying liver disease.
Prophylactic therapy may be employed to reduce the incidence of bleeding in patients with oesophageal varices before the first episode of variceal haemorrhage. Measures used include routine surveillance gastroscopy, sclerotherapy, banding and the use of β-blockers. Even though the incidence of bleeding is reduced, the effect on overall mortality is not affected.
The presence of ascites is a bad prognostic sign and usually indicates severe underlying liver disease. It results from a combination of portal hypertension, altered fluid and electrolyte imbalance and hypoalbuminaemia. Major complications of ascites include primary peritonitis and renal failure (hepatorenal syndrome).
Evaluation should include a detailed history and examination for the presence of ascites, portal hypertension and the severity of the underlying liver disease. Liver and renal biochemistry should be performed. An ascitic tap is undertaken and the ascitic fluid tested for bacteriology and albumin content.
The management of ascites should initially include sodium and fluid restrictions and specific diuretics which block tubular reabsorption of sodium (spironolactone). If these measures are unsuccessful, large volume paracentesis and intravenous infusion of albumin should be considered. For a small percentage of patients with refractory ascites despite these measures, consideration should be given to performing TIPS.
Liver transplantation should be considered in patients with chronic liver disease and intractable ascites. Liver transplantation is also indicated in patients with encephalopathy and progressive liver disease.
This is a complex neuro-psychiatric syndrome with a wide spectrum of clinical manifestations. It may occur due to the loss of hepatocellular function or the formation of porta-systemic shunts which bypass the liver parenchyma. The underlying cause for the encephalopathy dictates the clinical outcomes.
The aetiology of porta-systemic encephalopathy is thought to be multifactorial. The most widely implicated substance is ammonia in the portal circulation. Other nitrogenous substances as well as amino acid imbalances and false neurotransmission have also been implicated. An increase in urea-splitting gut bacteria, gastrointestinal haemorrhage and protein-rich diet may all increase the ammonia content of the portal venous blood. Reduction in intestinal bacteria by oral antibiotics, prevention of gastrointestinal haemorrhage and strict dietary measures contribute to minimising their effects. In addition changes in cerebral neurotransmitters have also been identified, making the brain of the encephalopathic patient more sensitive to insults that would not affect normal individuals.
Assessment should include detailed history and examination. Patients may often be unable to provide coherent history depending on the severity of encephalopathy. Clinical features include alterations in conscious state along with slurring of speech. More subtle changes may be seen in chronic porta-systemic encephalopathy. These include personality changes and intellectual deterioration. The most characteristic neurological abnormality is the ‘flapping tremor’ hat occurs with attempted dorsi-flexion of the wrist. The Reitan trail-making test, where the patient is required to connect numbers on a test page is a routinely used objective test of higher function.
Definitive diagnosis of hepatic encephalopathy may be achieved by electroencephalogram supported by CT evidence of chronic cerebral atrophy. The latter also serves to exclude other causes of impaired consciousness, including intra-cranial haemorrhage and tumours.