Hepatopancreatobiliary

Portal hypertension Causes of portal hypertension

and ascites Prehepatic portal hypertension

Thrombosis of the portal vein
Muhammad S Mirza Intra-abdominal sepsis
Guruprasad P Aithal Chronic pancreatitis
Pancreatic neoplasia
Prothrombotic state
Thrombosis of the splenic vein
Chronic pancreatitis
Pancreatic neoplasia
Abstract Splanchnic arteriovenous fistula
Portal pressure is the product of portal blood flow and resistance; an Intrahepatic portal hypertension
increase in either leads to increased portal pressure. Cirrhosis is the Predominantly pre-sinusoidal involvement
underlying cause in most cases, but portal hypertension can develop due Cirrhosis (alcoholic liver disease, viral hepatitis, non-alcoholic
to pre-, intra- and post-hepatic obstruction to the flow, secondary to variety fatty liver disease, primary biliary cirrhosis, primary sclerosing
of causes. Diagnosis can be established by a combination of non-invasive cholangitis, autoimmune hepatitis, haemochromatosis)
imaging of portal vasculature and clinical or serological markers for the Schistosomiasis
cause underlying cirrhosis. Development of gastro-oesophageal varices and Nodular regenerative hyperplasia
ascites are the most important clinical manifestation of portal hypertension. Polycystic disease
Non-selective beta-blockers and endoscopic band ligation are effective in Myeloploriferative diseases
primary and secondary prevention of variceal bleeding. Active variceal Hepatic metastases
haemorrhage is managed using a combination of vasoactive drugs (e.g. ter- Granulomatous (sarcoidosis, tuberculosis)
lipressin) and endoscopic band ligation. If these measures fail, transjugular Predominantly post-sinusoidal involvement
intrahepatic portosystemic stent (TIPS) insertion achieves haemostasis. BuddChiari syndrome
Diuretic therapy with spironolactone and furosemide are the mainstays of Veno-occlusive disease
management of ascites. If ascites becomes refractory, repeat large-volume Post-hepatic portal hypertension
paracentesis and TIPS in selected cases help to control symptoms. Devel- Constrictive pericarditis
opment of ascites is an important landmark in the natural history of cirrho- Obstruction of the inferior vena cava
sis and liver transplantation should be considered definitive treatment. Right heart failure
Tricuspid regurgitation
Keywords cirrhosis; ascites; TIPS; varices
Table 1

of portal hypertension. In cirrhosis, increased sinusoidal pressure

Definition
Portal pressure is the product of portal blood flow and intra-
hepatic resistance. Conditions that cause an increase in flow or
resistance increase portal pressure. Portal hypertension is a portal
venous pressure of >5 mmHg. Transjugular hepatic venous cath-
eterization is used to measure free and wedged hepatic venous
pressures. The clinical consequences of portal hypertension
occur if hepatic vein pressure gradient is 10 mmHg.
Aetiology and pathogenesis
Portal hypertension is classified according to the site of the
obstruction to blood flow into pre-hepatic, intrahepatic and
post-hepatic causes (Table 1). Cirrhosis is the commonest cause
Muhammad S Mirza FRCS(Ed) is a Research Fellow in General Surgery
at Derby City General Hospital, Derby, UK. Conflicts of interest: none
declared.
due to fibrosis and regenerative nodules is amplified by reduced
concentrations of vasodilators (e.g. nitric oxide). Concentrations
of nitric oxide are increased in the splanchnic and systemic circu-
lation probably due to gut-derived endotoxaemia. These haemo-
dynamic changes eventually lead to the clinical manifestations of
portal hypertension (Figure 1).
Clinical features
History-taking should be directed towards determining the cause
and complications of portal hypertension (Table 2). The physical
signs of chronic disease of the liver (e.g. spider naevi, red palms,
gynaecomastia) suggest cirrhosis as a cause of portal hypertension.
Ascites in portal hypertension rarely develops in the absence of cir-
rhosis and is detected in only 10% of patients with thrombosis of
the portal vein. Weight gain may be the early sign of fluid accumu-
lation before ascites becomes clinically detectable. Ascites indicates
decompensated liver disease and is a marker of poor prognosis.

Investigations
Guruprasad P Aithal FRCP is a Consultant Hepatologist and Special
Lecturer at University Hospital, Nottingham, UK. Conflicts of interest: Evaluation should be individualized depending on the presenta-
none declared. tion. Investigations should aim to confirm liver disease and to

SURGERY 25:1 28 2006 Elsevier Ltd. All rights reserved.

 Hepatopancreatobiliary

Pathogenesis of portal hypertension Increased concentration of nitric oxide in

the splanchnic and peripheral systems
Altered architecture; reduced Cirrhosis
concentration of nitric oxide
within the liver
Splanchnic and systemic
vascular resistance
Intrahepatic resistance

Sinusoidal pressure Portosystemic gradient Portal inflow Effective arterial blood volume

Ascites Collaterals Activated neurohumoral

systems

Retention of salt and water

Figure 1

identify the underlying cause (Table 3). Sequestration of white

blood cells associated with splenomegaly usually leads to pan-
cytopenia and cirrhosis is associated with an abnormal clotting
profile. Chronic viral hepatitis can be diagnosed using hepatitis-B
and -C serology. Autoantibody and immunoglobulin profiles
Clinical features of portal hypertension point towards the diagnosis of autoimmune liver diseases. Diag-
nosis of haemochromatosis can be established with raised iron
History indices and HFE genotyping. Metabolic syndrome predisposes to
Risk factors for cirrhosis non-alcoholic fatty liver disease and is a cause of cirrhosis.
Intravenous drug abuse
Infusion of blood products Imaging: abdominal ultrasound can establish ascites and
Metabolic syndrome (diabetes, obesity, hypertension, s plenomegaly. Duplex Doppler ultrasound allows imaging of the
dyslipidaemia) portal vein and its major tributaries, as well as the hepatic veins.
Alcohol abuse Imaging and flow patterns in the hepatic veins are particularly
Risk factors for non-cirrhotic portal hypertension important to exclude thrombosis of the hepatic vein. Portal cir-
Chronic pancreatitis, pancreatic cancer culation can be evaluated using CT and MRI if Doppler studies
Procoagulative disorders
Symptoms of gastrointestinal bleeding
Haemetemesis
Malena Specific investigations in portal hypertension
Haematochezia
Hypovolaemic shock To identify the causes of cirrhosis
Physical signs Liver function tests
Signs of portal hypertension Viral hepatitis-B and -C serology
Dilated veins in the anterior abdominal wall with flow away Antinuclear, antimitochondrial, anti-smooth muscle antibody
from the umbilicus Iron indices (ferritin, transferrin saturation)
Ascites 1-antitrypsin
Splenomegaly Caeruloplasmin (in those aged <40 years)
Caput medusae Liver biopsy
Signs of liver disease Portal vascular imaging
Jaundice Duplex Doppler ultrasonography
Spider naevi CT or MRI angiography/portography
Palmer erythema Transjugular hepatic venous pressure gradient
Asterixis Consequences of portal hypertension
Gynaecomastia Endoscopy of the upper gastrointestinal tract

Table 2 Table 3

SURGERY 25:1 29 2006 Elsevier Ltd. All rights reserved.

 Hepatopancreatobiliary

are inconclusive. MRI angiography can detect portosystemic

collaterals and obstruction of portal vascular structure. Selec- Portosystemic collaterals in portal
tive angiography of the superior mesenteric artery or splenic hypertension (schematic)
artery may be indicated in certain instances if other tests are
Oesophageal varices
inconclusive.

Hepatic venous pressure gradient is the gold standard for

defining and assessing the severity of portal hypertension, but
has limited applications in routine clinical practice in the UK.
Liver

Gastro-oesophageal varices
One of the main consequences of portal hypertension is the
development of extensive portal systemic collaterals (Figure 2). Portal vein
The collateral circulatory bed develops through a dynamic inter-
play of distinct physiological processes, including:
raised sinusoidal pressure (in cirrhosis)
Spleen
vasodilation
vascular remodelling
angiogenesis. Left gastric vein
Nitric oxide and vascular endothelial growth factor have impor- Splenic vein
tant roles in each of the steps of formation of collateral vessels.
Collaterals form predominantly due to dilation of pre-existent Gastric varices
embryonic channels. The left gastric vein is the main vessel Short gastric vein
responsible for the development of oesophageal varices; short
gastric veins lead to the dilation of fundal and gastro-oesophageal Figure 3
varices (Figures 2 and 3). Significant portosystemic collaterals
can also develop in the rectum, periumbilical, retroperitoneal
and peristomal regions (ectopic varices).
In cirrhosis, the prevalence of varices at diagnosis ranges from by ChildPugh class; see Malignant tumours of the liver, page
010% of patients with compensated disease to 7080% of those 34) is likely to be associated with significant thrombocytopenia.
with decompensated cirrhosis. The tension in the variceal wall Combination of these clinical parameters increases the prob
increases with increasing wedged hepatic venousportal gradi- ability of variceal bleeding. Variceal rupture accounts for about
ent and the size of the varix. This is manifested by cherry red 15% of haemorrhages of the upper gastrointestinal tract (see
spots and red wale markings. Advanced cirrhosis (as indicated Peterson, CROSS REFERENCES).

Management of gastro-oesophageal varices

Primary prevention: annual endoscopy of the upper gastro
intestinal tract can detect newly formed varices. Non-selective
Portosystemic collaterals and oesophageal -blockers (e.g. propranolol) reduce portal flow and pressure by
varices (schematic) decreasing cardiac output (1 receptors) and splanchnic arte-
rial flow (2 receptors). This halves the risk of first variceal
bleeding.
Para-oesophageal
Endoscopic band ligation should be considered:
vein Oesophageal varices if -blockers are contraindicated (asthma, peripheral vascular
Perforating vein disease, heart failure)
for those intolerant to the medication.
Posterior branch The benefits of banding outweigh the risks in high-risk groups
Cardiac
venous (moderate/large varices, advanced cirrhosis).
Left gastric vein plexus
Treatment of acute variceal haemorrhage: the goals of man-
Anterior agement are to resuscitate adequately, achieve haemostasis and
branch prevent rebleeding.
Resuscitation follows the rules of airway, breathing and cir-
culation. Restitution of blood volume should be done cautiously
and conservatively using plasma expanders to maintain hae-
modynamic stability and packed red blood cells to maintain
haemoglobin concentration at 810 g/dl (depending on the
Figure 2 haemodynamic status, ongoing bleeding and comorbidities; see

SURGERY 25:1 30 2006 Elsevier Ltd. All rights reserved.

 Hepatopancreatobiliary
Mackenzie, CROSS REFERENCES). Patients with hepatic enceph-
alopathy with large haemetemesis are at risk of aspiration and
may need airway protection, particularly during endoscopy of
the upper gastrointestinal tract.
Pharmacological therapy vasoactive drugs should be
started as soon as possible (even before diagnostic endoscopy)
if the suspicion of variceal bleeding is high. Terlipressin and
octreotide reduce splanchnic blood flow and facilitate cessa-
tion of bleeding. Treatment is maintained for 35 days from the
onset.
Endoscopy of the upper gastrointestinal tract should be done
with adequate airway protection using endotracheal intubation
if the risk of aspiration is high. Endoscopy helps to establish the
cause of upper gastrointestinal bleeding; non-variceal sources
(e.g. ulcers, MalloryWeiss tear, portal hypertensive gastro
pathy) account for the bleeding in 1525% of patients with cir-
rhosis. Variceal ligation (banding) is the preferred treatment if
oesophageal varices are the cause of bleeding. Injection sclero-
therapy may be used in the acute setting if ligation is technically
difficult.
Variceal sclerotherapy and ligation have not been shown to be
effective in the treatment of gastric varices. Injection with tissue
adhesive (e.g. N-butyl-cyanoacrylate) is superior (Figure 4), but
should be done only by an experienced endoscopist.
Balloon tamponade (SengstakenBlakemore tube) should be
used as a temporary measure in cases of massive bleeding. The
tube can be inserted via the nose or mouth and the gastric balloon
inflated with about 250 ml of air. Gentle traction is applied to the
tube (using a 250 ml fluid bag) so that the balloon tamponade
assists haemostasis. The SengstakenBlakemore tube achieves
control of bleeding in 90% of cases, but is associated with a
high risk of aspiration, so adequate airway protection (prefer-
ably with endotracheal intubation) is crucial. The gastric balloon
should not be kept inflated continuously for >24 hours. Inflation
of the oesophageal balloon is necessary only in exceptional cir-
cumstances. The pressure should be maintained at 2040 mmHg
when the oesophageal balloon is inflated; the balloon should be
Injection of histoacryl glue into gastric varices. a Shows the injection needle being inserted into gastric varix. b Shows a column of blood
extruding from the injection site. c Shows solidification of the blood in the process (i.e. haemostasis).
Figure 4
SURGERY 25:1
deflated for 24 minutes every hour to avoid pressure necrosis
of the oesophagus.
Transjugular intrahepatic portosystemic shunt (TIPS) acts
as a side-to-side portocaval shunt. It controls acute variceal
bleeding that is refractory to a combination of medical and
endoscopic management. This combination controls bleeding in
8090% of bleeding episodes; TIPS is used as salvage therapy if
endoscopic therapy fails to control bleeding.
A needle is inserted under fluoroscopic guidance from the
right hepatic vein to the right portal vein. The track is dilated
to 812 mm and a metal stent is deployed to support the shunt
wall. TIPS is effective in controlling bleeding due to portal
gastropathy.
Antibiotic prophylaxis up to 20% of cirrhotic patients
hospitalized due to gastrointestinal bleeding have bacterial
infections; an additional 50% develop an infection while hos-
pitalized. Besides a higher mortality, bacterial infections are
also associated with a higher rate of variceal bleeding. Anti-
biotics prevent bacterial infections and spontaneous bacterial
peritonitis.
Prevention of hepatic encephalopathy lactulose by mouth
or via nasogastric tube may reduce the risk of encephalopathy by
decreasing the nitrogenous load from the gut.
Nutrition malnutrition contributes to morbidity and mortal-
ity in these patients (see Kaushal, CROSS REFERENCES), so feed-
ing should be resumed as soon as possible. A nasogastric tube
can be inserted about 24 hours after bleeding stops.
Surgical management surgery has a limited role in the
management of acute variceal bleeding; TIPS is a less invasive
method of decompressing the varices. Emergency portocaval
shunts, oesophageal transection and devascularization are rarely
done.
Patient selection is crucial in determining the success of
surgical portosystemic shunts and can be done using the
ChildPugh classification. Shunt surgery in patients with Child
Pugh type-C cirrhosis carries a significant mortality, while
liver transplantation offers improved survival in this group of
31 2006 Elsevier Ltd. All rights reserved.
 Hepatopancreatobiliary
patients. Benefits and risks of liver transplantation should be
compared with those for shunt surgery In ChildPugh type-C and
type-B patients. Side-to-side lienorenal shunt is a good option if
other therapies have failed. Shunt surgery could be considered
in selected patients with non-cirrhotic portal hypertension if
endoscopic intervention has been unsuccessful and TIPS is not
feasible.
Secondary prevention: overall, about 70% of patients who
have had one episode of variceal bleeding rebleed. Non-selective
-blockers are the first-line treatment for the prevention of rebleed-
ing. Endoscopic ligation to eradicate the varices is required if:
the patient is non-compliant
the patient is intolerant to -blockers
-blockers are contraindicated
the patient is high risk (ChildPugh type-C, large varices).
Ascites
Ascites is an abnormal amount of intraperitoneal fluid; it is a
major complication of cirrhosis, occurring in 50% of patients
during ten years of follow-up. Ascites is an important landmark
in the natural history of cirrhosis because it is associated with a
50% mortality over two years and signifies the need to consider
liver transplantation as a therapeutic option. Seventy-five percent
of patients who present with ascites have underlying cirrhosis;
others are due to:
malignancy (10%)
heart failure (3%)
tuberculosis (2%)
pancreatitis (1%) and other rare causes.
The mechanism by which ascites develops is summarized in
Figure 1. Portal hypertension associated with cirrhosis is a
critical factor in the pathogenesis, and is associated with cir-
culatory changes characterized by arterial vasodilation, effec-
tive circulatory hypovolaemia, and the retention of sodium
and water in the kidney. The rapid and high inflow of arte-
rial blood into the splanchnic microcirculation is an additional
factor increasing hydrostatic pressure in the portal circulation.
Concentrations of albumin in plasma have little influence on
the rate of ascites formation.
Investigations
The underlying cause of ascites is usually obvious from his-
tory-taking and physical examination, but other causes of
ascites must be excluded. The essential investigations on
admission include diagnostic paracentesis (see below) and
abdominal ultrasound. Blood tests (urea and electrolytes,
liver function tests, prothrombin time, full blood count)
should be done.
Diagnostic paracentesis entails removal of ascitic fluid from the
peritoneal cavity using a needle. This is done 15 cm lateral to the
umbilicus, usually in the left lower quadrant of the abdomen.
Twenty millilitres are withdrawn for inoculation into blood cul-
ture bottles and the tests outlined below carried out. Diagnostic
paracentesis can be done without fresh frozen plasma or platelet
infusions despite the coagulopathy and thrombocytopenia seen
in most cirrhotic patients.
SURGERY 25:1
The serum-ascites albumin gradient is calculated by sub-
tracting the ascitic fluid albumin concentration from the
serum albumin; it is far superior in classifying ascites (97%
accuracy) than the classification based on ascitic fluid protein
concentration.
A value of 11 g/l suggests that ascites is due to cirrhosis with
portal hypertension or other causes of transudates (e.g. cardiac
failure, nephritic syndrome).
A value of <11 g/l is a feature of exudates secondary to
tuberculosis, malignancy and pancreatitis. High concentrations
of ascitic amylase are diagnostic of pancreatic ascites.
Ascitic fluid neutrophil count and culture an ascitic
neutrophil count of >250 cells/mm3 is diagnostic of spontaneous
bacterial peritonitis in the absence of a known perforated vis-
cus or inflammation of intra-abdominal organs. Injecting ascites
fluid into blood culture bottles at the bedside doubles the chance
of identifying the organism in cases of spontaneous bacterial
peritonitis.
Other tests requests for ascitic fluid cytology and culture for
mycobacteria should be done only if clinical suspicion of malig-
nancy or tuberculosis is high.
Management
Restriction of dietary salt: a no added salt diet of 90 mmol/day
(5.2 g salt/day) is adequate. A low salt diet eliminates ascites in
1020% of patients.
Fluid restriction: there is no role for water restriction in
patients with uncomplicated ascites. Impaired free water clear-
ance is seen in 2560% of patients with ascites due to cir-
rhosis, and many develop spontaneous hyponatraemia. Fluid
restriction to 1.5 l/day is common practice in patients with
hyponatraemia <125 mmol/l, but this may exacerbate the
effective central hypovolaemia that drives the non-osmotic
secretion of antidiuretic hormone. This may further increase
circulating antidiuretic hormone and lead to worsening of renal
function. Correction of effective hypovolaemia with 200 ml of
20% albumin to inhibit the stimulation of antidiuretic hormone
release should be considered. Emerging data support specific
vasopressin-2 receptor antagonists in the treatment of dilu-
tional hyponatraemia.
Diuretics: the first-line treatment of ascites should be spirono-
lactone alone, increasing from 100 mg/day to 400 mg/day. A
stepped-care approach is used, starting with modest restriction
of dietary salt together with an increasing dose of spironolac-
tone. If this fails, frusemide (up to 160 mg/day) is added with
careful biochemical and clinical monitoring. Spironolactone and
frusemide act synergistically.
Therapeutic paracentesis is the first-line treatment for large-
olume or refractory ascites. Large-volume paracentesis with
v
colloid replacement is rapid, safe and effective. Paracentesis of
<5 l of ascites should be followed by plasma expansion with a
synthetic plasma expander; volume expansion with albumin is
not required. Large-volume paracentesis (>5 l) should be done
in a single session with volume expansion using 8 g albumin/l
(100 ml of 20% albumin per 2.5 l of ascites drained). Failure to
give volume expansion can lead to post-paracentesis circulatory
32 2006 Elsevier Ltd. All rights reserved.
 Hepatopancreatobiliary

dysfunction, resulting in renal impairment and electrolyte dis-

turbances. After paracentesis, ascites recurs in about 93% of Complications of ascites
patients if diuretic therapy is not instituted.
Spontaneous bacterial peritonitis
TIPS can be used for the treatment of refractory ascites requiring Hepatorenal syndrome
frequent paracentesis or hepatic hydrothorax. TIPS: Umbilical hernia
reduces portal pressure Pleural effusion
decreases the activation of the reninangiotensinaldosterone Respiratory difficulties
system (see Lote, CROSS REFERENCES)
increases sodium excretion. Table 4
Control of ascites is achieved in 90% of cases and complete
resolution in 75% of cases. TIPS has been shown to resolve have an overall one-year survival after liver transplantation of
hepatic hydrothorax in 6070% of patients. Recently, with 85%.
polytetrafluoroethylene-covered stents, the long-term outcome
from TIPS has improved with lowered frequency of hepatic
encephalopathy (25% with standard stents). TIPS is associ-
ated with a less favourable outcome in advanced ChildPugh Cross references
class-C patients. Kaushal MV, Farrer K, Anderson ID. Nutritional support. Surgery 2004;
22(8): 196200.
Surgical shunts Lote C. The reninangiotensin system and regulation of fluid volume.
Peritoneovenous shunts have been used effectively in the Surgery 2006; 24(5): 1549.
management of refractory ascites, particularly if therapeutic Mackenzie I. Fluid and electrolyte balance, anaemia and blood
paracentesis and TIPS are unfeasible. Complications include: transfusion. Surgery 2005; 23(12): 45360.
shunt infection Peterson M, Thomas WEG. Gastrointestinal haemorrhage. Surgery 2005;
occlusion 23(6): 21722.
cocoon formation (making future transplantation difficult)
significant mortality.
Portocaval shunts (particularly side-to-side) have high surgi- Further reading
cal mortality, but may have to be considered if other treatments Boyer TD, Haskal ZJ. The role of transjugular intrahepatic portosystemic
are inappropriate. shunt in the management of portal hypertension. Hepatology 2005;
41: 386400.
Liver transplantation should be considered in patients with cir- Garcia-Tsao G. Current management of the complications of cirrhosis
rhotic ascites (particularly if resistant or refractory). The develop- and portal hypertension: variceal haemorrhage, ascites, and
ment of ascites is associated with a mortality of 50% within two spontaneous bacterial peritonitis. Gastroenterology 2001; 120:
years of diagnosis; prognosis is worse if complications (Table 4) 72648.
develop. Moore KP, Aithal GP. Guidelines on the management of ascites in
Fifty percent of patients die within six months if ascites cirrhosis. Gut 2006; 55(suppl 6): 12.
becomes refractory to medical therapy. Therapeutic paracentesis Orug T, Soonawalla ZF, Tekin K, Olliff SP, Buckels JA, Mayer AD. Role of
and TIPS do not improve long-term survival without transplan- surgical portosytemic shunts in the era of interventional radiology
tation for most patients. Patients with ascites due to cirrhosis and liver transplantation. Br J Surg 2004; 91: 76973.

SURGERY 25:1 33 2006 Elsevier Ltd. All rights reserved.