HEPATOBILIARY SURGERY

Portal hypertension and Causes of portal hypertension

ascites Pre-sinusoidal Sinusoidal Post-sinusoidal

Pre-hepatic Cirrhotic Intrahepatic

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

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 HEPATOBILIARY SURGERY

Some patients have dilated umbilical veins (‘caput medusae’) Management

due to recanalization of remnant porto-systemic collaterals of the
Primary prophylaxis of variceal bleeding
fetal umbilical circulation. Back-pressure on the spleen can cause
Patients should undergo endoscopic screening for varices at the
vascular engorgement and splenomegaly.
time of diagnosis of cirrhosis or portal hypertension. Primary
prophylaxis of bleeding in oesophageal varices involves a choice
Evaluation
between non-selective b-blockade and endoscopic treatment of
On initial routine blood investigations (full blood count, urea varices with band ligation. There is strong evidence that b-
and electrolytes, liver function tests and coagulation profile), blockers decrease bleeding risk in varices that are large enough
hyperbilirubinaemia and hypoalbuminaemia may be evident. to not collapse with air insufflation during endoscopy (grade II
Hypersplenism could be apparent from anaemia, thrombocy- varices). However, endoscopic treatment is preferred when there
topenia and leucopenia. Patients with poor synthetic liver are contraindications or intolerances to the use of non-
function may have a prolonged prothrombin time. If the un- cardioselective b-blockers. Currently, propranolol is the
derlying aetiology of liver disease is unclear, a blood liver preferred option in UK guidelines, with carvedilol or nadolol as
screen to detect the underlying cause should encompass hepa- alternatives. The dose is titrated to the maximum tolerated or a
titis B and C serology, autoantibody levels, immunoglobulin heart rate of 50e55 beats per minute.
profile, caeruloplasmin, a-1-antitrypsin, iron indices and hae-
mochromatosis genotyping. Management of variceal haemorrhage
Endoscopy is the investigation of choice for identifying varices In all severe upper gastrointestinal bleeds, including variceal
once a diagnosis of cirrhosis or portal hypertension is made. bleeding, the primary objective must be airway protection, with a
Capsule endoscopy is not a substitute for endoscopy but may be low threshold for endotracheal intubation if needed. Resuscita-
an option in patients that cannot tolerate endoscopy. Doppler tion should be commenced in a critical care environment with
ultrasonography is a worthwhile initial imaging modality, which suitable blood products available according to the major hae-
can identify splenomegaly, presence of ascites, liver structure morrhage protocols of each institution. Coagulopathy should be
and vasculature including portal vein patency, hepatic vein corrected and vasoactive agents (terlipressin or somatostatin)
patency and flow velocities. Transient elastography uses the administered as soon as possible, then continued until haemo-
principles of ultrasound to determine tissue stiffness, which re- stasis is achieved or for up to 5 days following the initial bleed.
lates to the degree of liver fibrosis. Magnetic resonance elastog- Prophylactic antibiotics providing Gram-negative cover are
raphy is an alternative technique that assesses the stiffness strongly recommended as they reduce mortality, infections and
though the whole liver but is less readily available. Invasive decrease re-bleeding.
angiography is not required as vascular anatomy can now be Endoscopic therapy is the first-line management step to prove
defined non-invasively by computed tomography and magnetic a variceal source of bleeding and to treat varices with band
resonance angiography. ligation. Endoscopic band ligation is the standard of care over
Hepatic venous pressure gradient (HPVG) is not routinely endoscopic sclerotherapy, as sclerotherapy is associated with
measured because it is invasive, resource intensive and requires higher rates of re-bleeding, mortality and stricture formation.
experienced interventional radiologists to perform hepatic vein However, in the management of gastric varices, endoscopic
catheterization. However, it is presently the best available tech- treatment with cyanoacrylate (a tissue adhesive) is more effec-
nique for gauging the presence and severity of portal hyperten- tive and also safer than band ligation. Due to the diffuse nature of
sion. Indeed, an HPVG of greater than 5 mmHg defines the bleeding in portal hypertensive gastropathy, the utility of endo-
presence of portal hypertension. Once the HPVG is over 10 scopic therapy is minimal but endoscopy is still required to
mmHg, the complications of portal hypertension start to develop, determine this diagnosis. The timing of endoscopy should be
with an HVPG greater than 12 mmHg marking the threshold for immediately after resuscitation in patients who are unstable and
variceal bleeding and ascites. within 24 hours of presentation in all other stable patients.
The incidence of varices, the risk of bleeding and mortality Medical therapy with endoscopic treatment is successful in 80
risk following a variceal bleed are related to increasing HPVG e85% of patients.
as well as the severity of underlying liver disease. Initial mor-
tality from uncontrolled variceal bleeding is approximately 6 ChildePugh classification
e8% and by 6 weeks following the primary bleed the mortality
rate increases to 25e30%. In patients with more advanced liver Measure 1 2 3
dysfunction, the mortality risk is 30e50% at 6 weeks. The degree
of liver failure has traditionally been classified using the Child Bilirubin (mmol/litre)a <34 34e50 >50
ePugh score, which along with bilirubin, albumin and pro- Albumin (g/litre) >35 28e35 <28
thrombin includes subjective grading of the degree of ascites and Prothrombin time (seconds prolonged) <4 4e6 >6
encephalopathy (both of which can be improved by therapy) Encephalopathy None Mild Marked
(Table 2). The model for end-stage liver disease (MELD) includes Ascites None Mild Marked
only objective measures of total serum bilirubin, Grade A ¼ 5e6 points; Grade B ¼ 7e9 points; Grade C ¼ 10e15 points.
a
serum creatinine, and prothrombin time so is used in the In primary biliary cirrhosis, the point scoring for bilirubin is adjusted as fol-
context of liver transplantation to assess and prioritize patients lows: 1  68, 2 ¼ 68e170, 3  170.

for listing.
Table 2

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 HEPATOBILIARY SURGERY

If bleeding is difficult to control, an oral-gastric tube (e.g. Management of non-cirrhotic portal hypertension
Sengstaken-Blakemore tube or Minnesota tube) should be Segmental portal hypertension from splenic vein thrombosis is a
inserted for temporary balloon tamponade of bleeding varices potential cause of bleeding gastric varices and should be sus-
until further endoscopic treatment, transjugular intrahepatic pected in patients with normal liver function and previous
portosystemic shunt (TIPSS) or (less commonly) surgery can pancreatic pathology (e.g. acute or chronic pancreatitis). Cura-
be undertaken. Depending on local resources and expertise, tive treatment involves splenectomy or splenic artery emboliza-
specialist input should be sought at this time and transfer to a tion. In BuddeChiari syndrome, anticoagulation is the first line
centre that provides an emergency TIPSS service should be of treatment, while endovascular therapy in the form of angio-
immediately arranged. plasty with stenting is used if anticoagulation fails. TIPSS is now
TIPSS is a minimally invasive interventional radiology pro- considered optimal treatment for BuddeChiari syndrome if initial
cedure performed by needle puncture from a hepatic vein to a anticoagulation and angioplasty are unsuccessful. Assessment
tributary of the intrahepatic portal vein under image guidance. for liver transplantation is advised for BuddeChiari syndrome
The track is maintained by a polytetrafluoroethylene covered when there is evidence of hepatic decompensation and jaundice.
stent so blood flow to the liver is preserved and decompression of Treatment of portal vein thrombosis depends on the presence of
the hypertensive portal system is achieved. Even after satisfac- symptoms, the precipitating cause, the presence of malignancy
tory haemostasis with endoscopic therapy, emerging evidence and cirrhosis. Conservative management is reasonable in
suggests that early TIPSS (<72 hours after primary variceal asymptomatic patients with an obvious reversible precipitant
haemorrhage) can be considered in selected patients to prevent (e.g. following intra-abdominal sepsis or pancreatitis). There is a
re-bleeding. Balloon tamponade is unlikely to be effective for low threshold for anticoagulation in patients with malignancy,
varices further down the stomach and early recourse to TIPSS for and in those with thrombosis extending into mesenteric veins or
bleeding gastric varices should be considered. The early post- progressing on serial imaging without treatment. In an emer-
procedural complications of TIPSS are due to the shunting of gency presentation with mesenteric ischaemia secondary to
portal flow directly into the venous system, which results in the portal vein thrombosis, thrombectomy or thrombolysis is indi-
accumulation of toxins and aggravates encephalopathy. Other cated and can be life saving. Endovascular options in the setting
procedure-related complications include liver parenchymal, of acute portal vein thrombosis include thrombolysis and TIPSS.
vascular and biliary injuries. Absolute contraindications to TIPSS
include severe heart failure, tricuspid regurgitation, multiple liver Management of ascites
cysts, uncontrolled sepsis, on-going biliary obstruction, and se- Ascites is an abnormal accumulation of excess intra-peritoneal
vere pulmonary hypertension. fluid. The pathophysiology is described in Figure 2. It is an
If TIPSS is unavailable or not feasible due to contra- important complication of cirrhosis and a significant develop-
indications, and local expertise exists, surgical shunting can be ment in the natural history of cirrhosis because it is associated
considered in ChildePugh A patients that are otherwise good with 50% mortality rate over 2 years. The majority of patients
surgical candidates. Surgical shunts have a lower risk of re- who present with ascites have underlying liver cirrhosis (75%).
bleeding and occlusion than TIPSS but a higher incidence of Other causes include malignancy (10%), heart failure (3%),
encephalopathy and no survival benefit. The direct porto-caval tuberculosis (2%) and pancreatitis (1%). The new development
shunt is a surgical technique that completely bypasses the liver of ascites should prompt investigation for spontaneous bacterial
by redirecting portal blood flow from the portal vein to the vena peritonitis, portal vein thrombosis or hepatic malignancy. If the
cava. This successfully reduces portal pressure but carries a high underlying cause is unclear, a diagnostic paracentesis should be
risk of encephalopathy. The selective distal splenorenal shunt is performed. This involves inserting a needle into the peritoneal
an alternative procedure that selectively decompresses the cavity (preferably under ultrasound guidance) to remove ascitic
oesophago-gastric and splenic area but maintains mesenteric fluid. Calculation of the serum-ascites albumin gradient is useful
portal blood flow to the liver and therefore has a lower rate of for establishing whether a transudate or exudate is present. This
encephalopathy. is determined by subtracting the ascitic fluid albumin concen-
An algorithm for the management of acute variceal bleeding is tration from the serum albumin concentration. A value of 11 g or
illustrated in Figure 1. more indicates transudative ascites (e.g. secondary to cirrhosis
and portal hypertension, cardiac failure, or nephrotic syndrome).
Secondary prophylaxis of variceal bleeding A value of less than 11 g is indicative of an exudate (e.g. sec-
Combination therapy with b-blockers and endoscopic band ondary to tuberculosis, malignancy and pancreatitis). Pancreatic
ligation are recommended for prophylaxis against variceal re- ascites may be evident from high concentrations of amylase in
bleeding. It is suggested that varices are banded at regular in- ascetic fluid. An ascitic neutrophil count of greater than 250
tervals until they are eradicated, with ongoing surveillance for cells/mm3 is diagnostic of spontaneous bacterial peritonitis in the
recurrent varices thereafter. TIPSS is reserved for those who re- absence of another known cause (e.g. perforated viscus). Bedside
bleed despite combination therapy. Recurrent variceal bleeding injection of ascitic fluid into blood culture bottles increases the
after initial successful management with endoscopic therapy chance of identifying the culprit organism and enables more
occurs in 30% of patients and requirement for salvage TIPSS is targeted antibiotic treatment. Ascitic fluid can also be sent for
associated with a high mortality. Shunt surgery can be recom- cytology and culture for mycobacteria if there is clinical suspi-
mended if surgical expertise permits in Child’s A patients when cion of malignancy or tuberculosis, respectively.
TIPSS is not possible. Ascites in cirrhosis can be managed by medical, surgical or
radiological techniques. Initial medical management involves

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 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 administered intravenously (100 ml per 2.5 litres of ascites
with the aldosterone inhibitor spironolactone (increasing from drained).
100 mg/day to 400 mg/day). If peripheral oedema is present, TIPSS is effective in controlling ascites that is unresponsive to
furosemide (up to 160 mg/day) can be added. Patients unre- medical treatment, but often these patients have liver failure with
sponsive to salt restriction and diuretics are described as having a poor overall prognosis in the absence of transplantation and as
refractory ascites, which puts them at risk of hepatorenal syn- such refractory ascites is an indication for transplant assessment.
drome, spontaneous bacterial peritonitis and hypovolaemic The immediate risk of TIPSS in this setting is worsening hepatic
hyponatremia. These patients may benefit from regular large- dysfunction, encephalopathy and death. Interventional
volume paracentesis. To avoid circulatory dysfunction, renal radiologically placed peritoneo-venous shunts can also be used in
impairment and electrolyte disturbances, 20% human albumin is 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
exceeding vasodilation FURTHER READING
increased
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Ascites
2010; Cd002907.
D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal
hypertension: an evidence-based approach. Semin Liver Dis 1999;
Renal Effective 19: 475e505.
sodium arterial volume Garcia-Pagan JC, Caca K, Bureau C, et al. Early use of TIPS in pa-
retention decreased tients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362:
2370e9.
Khan S, Tudur Smith C, Williamson P, Sutton R. Portosystemic shunts
versus endoscopic therapy for variceal rebleeding in patients with
Figure 2
cirrhosis. Cochrane Database Syst Rev, 2006; Cd000553.
Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for
peritoneal cavity back into the internal jugular vein or the superior treatment of esophageal variceal bleeding. A meta-analysis. Ann
vena cava. Complications include occlusion, infection, coagulop- Intern Med 1995; 123: 280e7.
athy, and leaks. Surgical shunts are no longer recommended for Monescillo A, Martinez-Lagares F, Ruiz-del-Arbol L, et al. Influence of
refractory ascites due to unacceptable perioperative mortality rates portal hypertension and its early decompression by TIPS place-
and likelihood of significant postoperative encephalopathy. ment on the outcome of variceal bleeding. Hepatol 2004; 40:
793e801.
Liver transplantation Zheng M, Chen Y, Bai J, et al. Transjugular intrahepatic portosystemic
shunt versus endoscopic therapy in the secondary prophylaxis of
The gold standard treatment for end-stage liver disease is liver
variceal rebleeding in cirrhotic patients: meta-analysis update.
transplantation. It offers the definitive treatment for portal hy-
J Clin Gastroenterol 2008; 42: 507e16.
pertension secondary to cirrhosis by curing the underlying liver

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