HEPATOBILIARY SURGERY

Portal hypertension and Causes of portal hypertension

ascites Pre-sinusoidal Sinusoidal Post-sinusoidal

Pre-hepatic Cirrhotic Intrahepatic

Stephen O’Neill
Gabriel C Oniscu
Abstract
Portal hypertension is secondary to increased resistance to blood flow
and increased blood flow through the portal system. The most com-
mon cause is liver cirrhosis. The most severe and life-threatening pre-
sentation of portal hypertension is acute variceal bleeding.
Pharmacotherapy with vasoactive agents (terlipressin or somato-
statin), endoscopic band ligation and radiological treatment with trans-
jugular intrahepatic portosystemic shunt (TIPSS) are the most
common treatment options for variceal bleeding. However, where sur-
gical expertise exists, portosystemic shunts can be considered for
refractory bleeding in patients without significant liver failure, espe-
cially when TIPSS is unavailable or contraindicated. Diuretic therapy
with spironolactone and furosemide are the basis for the management
of ascites. If ascites becomes refractory, repeat large volume para-
centesis and TIPSS are potential treatment options. Liver transplanta-
tion offers the definitive treatment for portal hypertension secondary to
cirrhosis as it cures the underlying liver disease.
Keywords Ascites; portal hypertension; variceal bleeding
Definition
Portal hypertension is an increase in portal blood pressure
(normal pressure range 5e10 mmHg) secondary to resistance to
blood flow and increased blood flow through the portal system.
Aetiology
The aetiology of portal hypertension can be classified as pre-
hepatic, intrahepatic and post-hepatic. Within the liver,
branches of the portal vein and hepatic artery give rise to sinu-
soids, which are low-pressure channels. Therefore, intrahepatic
conditions that lead to portal hypertension can be further cate-
gorized into pre-sinusoidal, sinusoidal and post-sinusoidal cau-
ses (Table 1). However, liver conditions can be associated with
high portal pressure at multiple levels. Intrahepatic causes of
portal hypertension are by far the most common. Liver cirrhosis
is accountable for portal hypertension in 90% of cases in the
Western world, with viral hepatitis and alcoholic liver disease as
the leading causes of cirrhosis. Schistosomiasis, sarcoidosis and
congenital hepatic fibrosis are pre-sinusoidal causes of portal
Stephen O’Neill MB BCh BAO MSc MFSTEd AFHEA MAcadMEd MRCSEd PhD
is a General Surgery Registrar at the Royal Infirmary of Edinburgh,
UK. Conflicts of interest: none declared.
Gabriel C Oniscu MBChB MD FRCS is a Consultant Transplant Surgeon
and NRS Career Research Fellow at the Royal Infirmary of Edinburgh
and Honorary Clinical Senior Lecturer at the University of Edinburgh,
UK. Conflicts of interest: none declared.
Portal vein thrombosis Post-viral (B, C) Veno-occlusive
disease
Splenic vein thrombosis Alcoholic
Increased splenic flow Cryptogenic Post-hepatic
e.g. myelofibrosis Primary biliary cirrhosis Budd-Chiari
Chronic active hepatitis Constrictive
pericarditis
Intrahepatic Haemochromatosis Caval web
Schistosomiasis Wilson’s disease
Congenital hepatic
fibrosis
Sarcoidosis Non-cirrhotic
Acute alcoholic
hepatitis
Cytotoxic drugs
Table 1
hypertension and are notable for the fact that hepatocellular ar-
chitecture and liver function remains well preserved.
Pathophysiology
In liver cirrhosis, fibrosis and regenerative nodules result in si-
nusoidal obstruction with increased vascular resistance to portal
blood flow. In addition, an active increase in intrahepatic
vascular tone occurs, which is thought to be a result of differ-
ences between the release of endogenous vasoconstrictors and
the vasodilator nitric oxide. In contrast, excess nitric oxide within
the splanchnic circulation causes vasodilation and leads to an
increase in portal blood flow. Pharmacological therapy for portal
hypertension, including vasoactive agents (terlipressin or so-
matostatin) and non-selective b-blockers (propranolol, carvedilol
or nadolol) target splanchnic circulation and aim to reduce the
blood flow. Portal hypertension results in shunting of blood
through collateral veins (e.g. left gastric vein and short gastric
veins) between the portal venous and systemic venous circula-
tion causing dilated vessels known as varices. The sites of varices
include the oesophagus, stomach, falciform ligament, retro-
peritoneum, surgically created stomas and anal canal. In portal
hypertension, ascites can also result from excess lymph and
reduced serum albumin as well as retention of salt and water
secondary to elevated antidiuretic hormone and aldosterone
levels.
Presentation
The most severe and life-threatening presentation of portal hy-
pertension is variceal bleeding. Other less acute presentations
include non-specific symptoms of chronic liver disease such as
tiredness, loss of appetite and weight loss. Advanced decom-
pensating liver failure can present with jaundice or confusion
with reduced consciousness level from hepatic encephalopathy.
Features on clinical examination may include jaundice, spider
naevi, palmar erythema, asterixis, gynaecomastia and ascites.

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 HEPATOBILIARY SURGERY
Some patients have dilated umbilical veins (‘caput medusae’)
due to recanalization of remnant porto-systemic collaterals of the
fetal umbilical circulation. Back-pressure on the spleen can cause
vascular engorgement and splenomegaly.
Evaluation
On initial routine blood investigations (full blood count, urea
and electrolytes, liver function tests and coagulation profile),
hyperbilirubinaemia and hypoalbuminaemia may be evident.
Hypersplenism could be apparent from anaemia, thrombocy-
topenia and leucopenia. Patients with poor synthetic liver
function may have a prolonged prothrombin time. If the un-
derlying aetiology of liver disease is unclear, a blood liver
screen to detect the underlying cause should encompass hepa-
titis B and C serology, autoantibody levels, immunoglobulin
profile, caeruloplasmin, a-1-antitrypsin, iron indices and hae-
mochromatosis genotyping.
Endoscopy is the investigation of choice for identifying varices
once a diagnosis of cirrhosis or portal hypertension is made.
Capsule endoscopy is not a substitute for endoscopy but may be
an option in patients that cannot tolerate endoscopy. Doppler
ultrasonography is a worthwhile initial imaging modality, which
can identify splenomegaly, presence of ascites, liver structure
and vasculature including portal vein patency, hepatic vein
patency and flow velocities. Transient elastography uses the
principles of ultrasound to determine tissue stiffness, which re-
lates to the degree of liver fibrosis. Magnetic resonance elastog-
raphy is an alternative technique that assesses the stiffness
though the whole liver but is less readily available. Invasive
angiography is not required as vascular anatomy can now be
defined non-invasively by computed tomography and magnetic
resonance angiography.
Hepatic venous pressure gradient (HPVG) is not routinely
measured because it is invasive, resource intensive and requires
experienced interventional radiologists to perform hepatic vein
catheterization. However, it is presently the best available tech-
nique for gauging the presence and severity of portal hyperten-
sion. Indeed, an HPVG of greater than 5 mmHg defines the
presence of portal hypertension. Once the HPVG is over 10
mmHg, the complications of portal hypertension start to develop,
with an HVPG greater than 12 mmHg marking the threshold for
variceal bleeding and ascites.
The incidence of varices, the risk of bleeding and mortality
risk following a variceal bleed are related to increasing HPVG
as well as the severity of underlying liver disease. Initial mor-
tality from uncontrolled variceal bleeding is approximately 6
e8% and by 6 weeks following the primary bleed the mortality
rate increases to 25e30%. In patients with more advanced liver
dysfunction, the mortality risk is 30e50% at 6 weeks. The degree
of liver failure has traditionally been classified using the Child
ePugh score, which along with bilirubin, albumin and pro-
thrombin includes subjective grading of the degree of ascites and
encephalopathy (both of which can be improved by therapy)
(Table 2). The model for end-stage liver disease (MELD) includes
only objective measures of total serum bilirubin,
serum creatinine, and prothrombin time so is used in the
context of liver transplantation to assess and prioritize patients
for listing.
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Management
Primary prophylaxis of variceal bleeding
Patients should undergo endoscopic screening for varices at the
time of diagnosis of cirrhosis or portal hypertension. Primary
prophylaxis of bleeding in oesophageal varices involves a choice
between non-selective b-blockade and endoscopic treatment of
varices with band ligation. There is strong evidence that b-
blockers decrease bleeding risk in varices that are large enough
to not collapse with air insufflation during endoscopy (grade II
varices). However, endoscopic treatment is preferred when there
are contraindications or intolerances to the use of non-
cardioselective b-blockers. Currently, propranolol is the
preferred option in UK guidelines, with carvedilol or nadolol as
alternatives. The dose is titrated to the maximum tolerated or a
heart rate of 50e55 beats per minute.
Management of variceal haemorrhage
In all severe upper gastrointestinal bleeds, including variceal
bleeding, the primary objective must be airway protection, with a
low threshold for endotracheal intubation if needed. Resuscita-
tion should be commenced in a critical care environment with
suitable blood products available according to the major hae-
morrhage protocols of each institution. Coagulopathy should be
corrected and vasoactive agents (terlipressin or somatostatin)
administered as soon as possible, then continued until haemo-
stasis is achieved or for up to 5 days following the initial bleed.
Prophylactic antibiotics providing Gram-negative cover are
strongly recommended as they reduce mortality, infections and
decrease re-bleeding.
Endoscopic therapy is the first-line management step to prove
a variceal source of bleeding and to treat varices with band
ligation. Endoscopic band ligation is the standard of care over
endoscopic sclerotherapy, as sclerotherapy is associated with
higher rates of re-bleeding, mortality and stricture formation.
However, in the management of gastric varices, endoscopic
treatment with cyanoacrylate (a tissue adhesive) is more effec-
tive and also safer than band ligation. Due to the diffuse nature of
bleeding in portal hypertensive gastropathy, the utility of endo-
scopic therapy is minimal but endoscopy is still required to
determine this diagnosis. The timing of endoscopy should be
immediately after resuscitation in patients who are unstable and
within 24 hours of presentation in all other stable patients.
Medical therapy with endoscopic treatment is successful in 80
e85% of patients.
ChildePugh classification
Measure 1 2 3
Bilirubin (mmol/litre)a <34 34e50 >50
Albumin (g/litre) >35 28e35 <28
Prothrombin time (seconds prolonged) <4 4e6 >6
Encephalopathy None Mild Marked
Ascites None Mild Marked
Grade A ¼ 5e6 points; Grade B ¼ 7e9 points; Grade C ¼ 10e15 points.
a
In primary biliary cirrhosis, the point scoring for bilirubin is adjusted as fol-
lows: 1  68, 2 ¼ 68e170, 3  170.
Table 2
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 HEPATOBILIARY SURGERY
If bleeding is difficult to control, an oral-gastric tube (e.g.
Sengstaken-Blakemore tube or Minnesota tube) should be
inserted for temporary balloon tamponade of bleeding varices
until further endoscopic treatment, transjugular intrahepatic
portosystemic shunt (TIPSS) or (less commonly) surgery can
be undertaken. Depending on local resources and expertise,
specialist input should be sought at this time and transfer to a
centre that provides an emergency TIPSS service should be
immediately arranged.
TIPSS is a minimally invasive interventional radiology pro-
cedure performed by needle puncture from a hepatic vein to a
tributary of the intrahepatic portal vein under image guidance.
The track is maintained by a polytetrafluoroethylene covered
stent so blood flow to the liver is preserved and decompression of
the hypertensive portal system is achieved. Even after satisfac-
tory haemostasis with endoscopic therapy, emerging evidence
suggests that early TIPSS (<72 hours after primary variceal
haemorrhage) can be considered in selected patients to prevent
re-bleeding. Balloon tamponade is unlikely to be effective for
varices further down the stomach and early recourse to TIPSS for
bleeding gastric varices should be considered. The early post-
procedural complications of TIPSS are due to the shunting of
portal flow directly into the venous system, which results in the
accumulation of toxins and aggravates encephalopathy. Other
procedure-related complications include liver parenchymal,
vascular and biliary injuries. Absolute contraindications to TIPSS
include severe heart failure, tricuspid regurgitation, multiple liver
cysts, uncontrolled sepsis, on-going biliary obstruction, and se-
vere pulmonary hypertension.
If TIPSS is unavailable or not feasible due to contra-
indications, and local expertise exists, surgical shunting can be
considered in ChildePugh A patients that are otherwise good
surgical candidates. Surgical shunts have a lower risk of re-
bleeding and occlusion than TIPSS but a higher incidence of
encephalopathy and no survival benefit. The direct porto-caval
shunt is a surgical technique that completely bypasses the liver
by redirecting portal blood flow from the portal vein to the vena
cava. This successfully reduces portal pressure but carries a high
risk of encephalopathy. The selective distal splenorenal shunt is
an alternative procedure that selectively decompresses the
oesophago-gastric and splenic area but maintains mesenteric
portal blood flow to the liver and therefore has a lower rate of
encephalopathy.
An algorithm for the management of acute variceal bleeding is
illustrated in Figure 1.
Secondary prophylaxis of variceal bleeding
Combination therapy with b-blockers and endoscopic band
ligation are recommended for prophylaxis against variceal re-
bleeding. It is suggested that varices are banded at regular in-
tervals until they are eradicated, with ongoing surveillance for
recurrent varices thereafter. TIPSS is reserved for those who re-
bleed despite combination therapy. Recurrent variceal bleeding
after initial successful management with endoscopic therapy
occurs in 30% of patients and requirement for salvage TIPSS is
associated with a high mortality. Shunt surgery can be recom-
mended if surgical expertise permits in Child’s A patients when
TIPSS is not possible.
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Management of non-cirrhotic portal hypertension
Segmental portal hypertension from splenic vein thrombosis is a
potential cause of bleeding gastric varices and should be sus-
pected in patients with normal liver function and previous
pancreatic pathology (e.g. acute or chronic pancreatitis). Cura-
tive treatment involves splenectomy or splenic artery emboliza-
tion. In BuddeChiari syndrome, anticoagulation is the first line
of treatment, while endovascular therapy in the form of angio-
plasty with stenting is used if anticoagulation fails. TIPSS is now
considered optimal treatment for BuddeChiari syndrome if initial
anticoagulation and angioplasty are unsuccessful. Assessment
for liver transplantation is advised for BuddeChiari syndrome
when there is evidence of hepatic decompensation and jaundice.
Treatment of portal vein thrombosis depends on the presence of
symptoms, the precipitating cause, the presence of malignancy
and cirrhosis. Conservative management is reasonable in
asymptomatic patients with an obvious reversible precipitant
(e.g. following intra-abdominal sepsis or pancreatitis). There is a
low threshold for anticoagulation in patients with malignancy,
and in those with thrombosis extending into mesenteric veins or
progressing on serial imaging without treatment. In an emer-
gency presentation with mesenteric ischaemia secondary to
portal vein thrombosis, thrombectomy or thrombolysis is indi-
cated and can be life saving. Endovascular options in the setting
of acute portal vein thrombosis include thrombolysis and TIPSS.
Management of ascites
Ascites is an abnormal accumulation of excess intra-peritoneal
fluid. The pathophysiology is described in Figure 2. It is an
important complication of cirrhosis and a significant develop-
ment in the natural history of cirrhosis because it is associated
with 50% mortality rate over 2 years. The majority of patients
who present with ascites have underlying liver cirrhosis (75%).
Other causes include malignancy (10%), heart failure (3%),
tuberculosis (2%) and pancreatitis (1%). The new development
of ascites should prompt investigation for spontaneous bacterial
peritonitis, portal vein thrombosis or hepatic malignancy. If the
underlying cause is unclear, a diagnostic paracentesis should be
performed. This involves inserting a needle into the peritoneal
cavity (preferably under ultrasound guidance) to remove ascitic
fluid. Calculation of the serum-ascites albumin gradient is useful
for establishing whether a transudate or exudate is present. This
is determined by subtracting the ascitic fluid albumin concen-
tration from the serum albumin concentration. A value of 11 g or
more indicates transudative ascites (e.g. secondary to cirrhosis
and portal hypertension, cardiac failure, or nephrotic syndrome).
A value of less than 11 g is indicative of an exudate (e.g. sec-
ondary to tuberculosis, malignancy and pancreatitis). Pancreatic
ascites may be evident from high concentrations of amylase in
ascetic fluid. An ascitic neutrophil count of greater than 250
cells/mm3 is diagnostic of spontaneous bacterial peritonitis in the
absence of another known cause (e.g. perforated viscus). Bedside
injection of ascitic fluid into blood culture bottles increases the
chance of identifying the culprit organism and enables more
targeted antibiotic treatment. Ascitic fluid can also be sent for
cytology and culture for mycobacteria if there is clinical suspi-
cion of malignancy or tuberculosis, respectively.
Ascites in cirrhosis can be managed by medical, surgical or
radiological techniques. Initial medical management involves
489 Ó 2020 Published by Elsevier Ltd.
 HEPATOBILIARY SURGERY

Secondary prophylaxis of variceal bleeding

Upper gastro-
intestinal bleed in
cirrhotic patient

Resuscitation

Consider intubation,
IV access and activate
major haemorrhage
protocols

Transfer to HDU
or ITU setting

Intravenous antibiotics
and vasoactive drugs

Urgent endoscopy

Oesophageal Gastric
varices varices

Band Injection of
ligation cyanoacrylate

Control of Continued Rescue

bleeding bleed or therapy
re-bleed with TIPSS

Secondary Selected patients Resuscitation

prophylaxis <72 hours from and balloon
index bleed tamponade

Rescue therapy
Early TIPSS
with TIPSS

TIPSS, transjugular intrahepatic portosystemic shunt.

Figure 1

dietary sodium restriction (5.2 g salt/day) and diuretic therapy
with the aldosterone inhibitor spironolactone (increasing from
100 mg/day to 400 mg/day). If peripheral oedema is present,
furosemide (up to 160 mg/day) can be added. Patients unre-
sponsive to salt restriction and diuretics are described as having
refractory ascites, which puts them at risk of hepatorenal syn-
drome, spontaneous bacterial peritonitis and hypovolaemic
hyponatremia. These patients may benefit from regular large-
volume paracentesis. To avoid circulatory dysfunction, renal
impairment and electrolyte disturbances, 20% human albumin is
administered intravenously (100 ml per 2.5 litres of ascites
drained).
TIPSS is effective in controlling ascites that is unresponsive to
medical treatment, but often these patients have liver failure with
a poor overall prognosis in the absence of transplantation and as
such refractory ascites is an indication for transplant assessment.
The immediate risk of TIPSS in this setting is worsening hepatic
dysfunction, encephalopathy and death. Interventional
radiologically placed peritoneo-venous shunts can also be used in
the treatment of refractory ascites. Shunts drain ascites from the

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 HEPATOBILIARY SURGERY

disease. Patients should be referred for transplant assessments

Pathophysiology of ascites when serious complications of cirrhosis develop, such as variceal
bleeding, ascites and encephalopathy. Patients will be considered
for liver transplantation if they have an anticipated life expec-
Portal
tancy (without transplantation) of less than 1 year or an unac-
hypertension
ceptable quality of life (e.g. chronic encephalopathy or
intractable pruritus) and providing that they have a projected
50% predicted 5-year post-transplant survival. A
Excess lymph
Vascular
formation Splanchnic
volume
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