Review articles

The Intensive Care Society 2013

Acute liver failure following hepatic

resection: incidence, presentation,
prevention and management in ICU
C Jones, L Kelliher, C Bigham, N Quiney

The incidence of liver failure following liver resection has been reported to be between 8-32%, depending on the number
of segments resected, the health of the patient and the incidence of hepatic ischaemic/reperfusion injury. This article
outlines the evidence surrounding classification, prevention and management of this condition.
Keywords: liver resection; liver failure; intensive care

Introduction
Mild liver dysfunction is occasionally seen following major
surgery. Acute liver failure is much rarer. Patients at greatest
risk of developing postoperative liver failure are those
undergoing liver resection, where the risk can be as high as
32%.1 When it does occur, acute liver failure is a devastating
complication, with a high morbidity and mortality.
The spectrum of liver dysfunction post-hepatic resection
encompasses everything from a transient rise in liver enzymes
to fulminant liver failure and death. The features include
coagulopathy, hyperbilirubinaemia, encephalopathy and
associated multiple organ failure. The most effective way to
reduce the impact of this complication is to prevent it
developing in the first instance, which requires a careful and
considered approach. Early identification of patients at risk and
prompt and appropriate management of those developing acute
liver failure is key.
The incidence of liver resection surgery is increasing as a
treatment for certain benign and malignant liver lesions. The
most common indication in the UK is for treatment of liver
metastases associated with colorectal cancer. Approximately
3,600 patients per year fit into this category, a figure that will
only increase with improvements in chemotherapy regimens.2
Hepatic resection is also performed in live-donor liver
transplantation.
Grade A

Post-hepatectomy liver failure resulting in abnormal

laboratory parameters but requiring no change in the
clinical management of the patient

Grade B

Post-hepatectomy liver failure resulting in a

deviation from the regular clinical management but
manageable without invasive treatment

Grade C

Post-hepatectomy liver failure resulting in a deviation

from the regular clinical management and requiring
invasive treatment

Table 1 ISGLS consensus severity grading of post-hepatectomy

liver failure.4

JICS Volume 14, Number 2, April 2013

This article reviews the management of post-hepatic

resection liver failure, strategies for preventing it and some
future directions in treatment.

Definition and incidence

Despite its potential severity, there is no universally accepted
definition of postoperative liver failure3 and therefore it is
difficult to accurately determine its incidence. The
International Study Group of Liver Surgery (ILSGLS) has
recently produced this definition:4

a postoperative acquired deterioration in the ability

of the liver to maintain its synthetic, excretory and
detoxifying functions, which is characterised by an
increased international normalised ratio and
concomitant hyperbilirubinemia on or after
postoperative day 5.
The group also differentiated the severity of postoperative
liver failure into three different grades from A to C, depending
on the level of treatment needed. Grade A encompasses
development of abnormal blood tests but no change in clinical
management; grade B suggests the degree of liver failure
needed clinical management but not invasive therapy; grade C
is acute postoperative liver failure requiring invasive treatment
(see Table 1).
Other methods that have been used to define postoperative
liver failure include the 50-50 criteria.5 A serum bilirubin
concentration above 50 mol/L and a prothrombin time (PT)
which is increased by more than 50% of baseline (or INR >1.7)
on postoperative day five is associated with a mortality of 59%
as opposed to 1.2% if these criteria are not met (sensitivity
69.6%, specificity 98.5%).
Another grading system6 used to predict the risk of
postoperative liver failure is demonstrated in Table 2. Values
should be present on two consecutive days during the
postoperative course. Points score 0=no dysfunction, 1-2=mild,
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Points

Total serum bilirubin (mol/L)

20

21-60

>60

Prothrombin time
(seconds above normal)

<4

4-6

>6

Serum lactate (mmol/L)

1.5

1.6-3.5

>3.5

Encephalopathy severity grade

None

1 and 2

3 and 4

Table 2 Severity of postoperative hepatic dysfunction score.6

3-4=moderate, >4= severe dysfunction.

The incidence of acute liver failure following hepatic
resection has been reported to be as high as 32% by some
authors,1 although others suggest it is nearer 8%. Schindl and
colleagues believe that the risk should be quoted as less than
1% in patients with no parenchymal disease and having small
resections; 10% when four segments are being resected and
30% for those having five or more segments resected.6
With advances in surgical and anaesthetic techniques,
mortality rates following liver resection surgery have decreased
from 20% in the 1970s8 to approximately 2% today.9
Postoperative hepatic insufficiency/failure accounts for between
60 and 100% of these deaths.5,6,10-12 Morbidity following liver
resection remains high, with rates between 15-35%.13-15

Causes of post-hepatic resection liver failure

Liver dysfunction is seen occasionally after any major surgery.
Periods of intraoperative hypoxia, hypotension, the use of
blood transfusions or development of sepsis can all result in
liver ischaemia and/or cellular dysfunction. Following liver
resection, intra-operative blood loss of more than one litre with
the need for blood transfusion increases the risk of
postoperative liver failure and sepsis.16,17 Sepsis has a
detrimental effect on liver function (by inhibiting Kupffer cell
function) and affects hepatic cell regeneration.18
A normal subject with no other risk factors can have up to
75% of their liver resected safely.19 The liver has a great
capacity to regenerate, and the remnant can increase by 100%
in size in as little as a week (although this is not reflected in a
concomitant increase in synthetic function).
The most important risk factors for postoperative liver
failure are:3,12
The size of resection
Evidence of preoperative liver parenchymal disease (eg
cirrhosis)
Hepatic ischaemia/reperfusion injury.
Removal of four or more segments (out of eight) is
associated with an increased risk of postoperative liver failure.
If the liver remnant is too small, there may not be enough
functioning hepatocytes for adequate synthesis, excretion and
detoxification. Another problem with small liver remnants is
hyperperfusion;20 the relative increase in blood flow causes
sinusoidal dilatation, haemorrhagic infiltration, centrilobar
necrosis and prolonged cholestasis, causing further impaired
synthetic function and inhibition of cell proliferation.3,20
Underlying liver disease reduces the functional and
regenerative capacity of the liver and therefore makes it more
susceptible to damage. A larger remnant volume needs to be
134

present at the end of surgery.3,18 Chemotherapy also affects liver

parenchyma and reduces its regenerative capacity. A recent
French study looked at 101 patients undergoing intensive
chemotherapy (6 cycles of the newer chemotherapy agents:
oxaliplatin and irinotecan) prior to undergoing liver resection.
They found that 50% of patients developed sinusoidal
obstruction syndrome and 10% steatohepatitis on histological
analysis (5% had both).20 Both sinusoidal injury and steatosis
from chemotherapy reduce the regenerative capacity of the
liver remnant and therefore increase the likelihood of
postoperative failure.3,22,23 Sinusoidal injury may also occur as a
result from small-for-size syndrome, when dysfunction occurs
after a living-donor partial graft. It is thought to be due to
portal hyperperfusion of the graft, combined with poor venous
outflow, resulting in sinusoidal congestion and endothelial
dysfunction.24 A similar picture can be seen after extensive
hepatic resection with a small liver remnant.
Vascular occlusive techniques used to reduce intraoperative
bleeding comprise either total occlusion of both inflow and
outflow, or total inflow occlusion. The Pringle manoeuvre
refers to the total occlusion of inflow, ie occlusion of hepatic
artery and portal vein inflow to the liver. This limits blood
supply to the liver, with the result that bleeding will principally
be a result of hepatic venous pressure, which itself can be
reduced by maintaining a low CVP intraoperatively. Occlusion
induces ischaemia in the liver remnant,25 resulting in hepatic
ischaemia/reperfusion injury, the generation of free radicals and
subsequent liver dysfunction. For this reason, the Pringle
manoeuvre is now used much less frequently26 and for less
than forty-five minutes in total during surgery.27
Other risk factors for postoperative liver failure include
age over sixty-five, as the ability of the liver to regenerate
decreases with age,28 diabetes mellitus and poor nutritional
status.3,18 Being male doubles the risk of developing
postoperative liver failure.29
Rarely, postoperative liver failure can result from altered
vascular supply. Portal or hepatic vein obstruction can occur
either through thrombosis, torsion or surgical injury. It is
worth considering these options and excluding them with an
ultrasound scan. Postoperative cholestasis can also muddy the
waters. It is often drug-induced (eg penicillin, erythromycin
and NSAIDs), but can occasionally be a result of the surgery
itself, or following total parenteral nutrition on the intensive
care unit. Occasionally an isolated increase in bilirubin can
occur, for example following a blood transfusion or in a patient
with Gilberts syndrome. Gilberts syndrome is present in 2-5%
of the population. A decreased activity of hepatic glucuronyl
transferase leads to an increase in unconjugated bilirubin.

Preventative strategies
Careful patient selection to ensure adequate
residual liver volume
In patients with normal liver parenchyma, a remnant as small
as 26% of the original livers volume can be safely left.6
However those with parenchymal diseases require a larger
residual volume (approximately 40%) to avoid postoperative
liver failure;19 a similar volume has been suggested for those
patients who have received intensive chemotherapy treatment
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(>6 cycles) prior to liver resection surgery.21 In that study, the

authors found that residual volumes of 44.8%, 43.1% and
37.7% were independent predictors of overall morbidity, sepsis
and liver failure respectively.
In patients with cirrhosis, resections should only be offered
in those with stable disease (ie Child-Pugh class A); only very
small resections in selected patients should be offered to patients
with Child-Pugh class B, and avoided in class C patients.
Where an extensive resection is planned, avoiding the
problems associated with a potentially small remnant can be
achieved by employing strategies such as preoperative
neoadjuvant chemotherapy to reduce the volume of tumour,
performing a staged hepatectomy or a preoperative portal vein
embolisation (PVE). PVE is one of the most useful strategies
there is in preventing postoperative liver dysfunction and
involves embolising one of the portal veins to induce liver
atrophy on the operative side and hypertrophy in the intended
remnant section.30

Choice of anaesthetic agents

The volatile anaesthetic agents metabolised in the liver are
known to alter hepatic blood flow and induce transient
changes in liver enzymes. The use of halothane, which on
repeated exposure may cause hepatitits (so-called halothane
hepatitis) is now uncommon. Other volatile agents, including
isoflurane, sevoflurane and desflurane, have minimal hepatic
metabolism and there is a lack of evidence demonstrating
hepatotoxicity.31 Total intravenous anaesthesia (TIVA) has been
advocated by some as a preferred option in liver surgery, but to
date there is no evidence to support this.

Minimise blood loss

Postoperative blood transfusions have an immunosuppressive
effect16 and, as stated above, the requirement for blood
transfusion following major blood loss increases the risk of
postoperative liver failure.16,17 Strategies to reduce blood loss
include: maintaining a low central venous pressure
(<5 mm Hg),32 avoidance of excessive PEEP, the use of thoracic
epidurals, furosemide, and the use of GTN and remifentanil
infusions.33 Tranexamic acid is an anti-fibrinolytic that
competitively inhibits the activation of plasminogen to plasmin
and can be used to reduce intraoperative blood loss. Surgical
techniques which can minimise blood loss include the use of
the CUSA (Cavitron Ultrasonic Surgical Aspirator), an
ultrasonic system used to dissect liver parenchyma. It uses
ultrasound at approximately 25 kHz, which has enough energy
to destroy liver parenchyma but not enough to damage
vascular structures.36 Haemostatic agents have also been used
to good effect.37 They are applied directly onto the cut surface
of the liver and contain granules of a gelatine matrix which
promote the formation of a fibrin polymer from fibrinogen.
Surgical use of the Pringle manoeuvre can also be used to
prevent blood loss, but with the added risk of causing
ischaemic damage.

oral carbohydrate loading and intravenous dextrose infusions,

reduce the rates of postoperative liver dysfunction, infections
and complications.40 Fisette and colleagues used insulin
infusions for all patients, (diabetics and non-diabetics), which
led to higher cell substrate availability, altered the inflammatory
response (decreased cytokines IL-6, IL-10, TNF- and CRP)
and decreased hepatocellular apoptosis. For these reasons,
insulin and dextrose infusions have been used by some as
treatment for postoperative liver dysfunction,40 although there
are no randomised controlled trials in this area.

Ischaemic preconditioning
Ischaemic preconditioning involves intermittent clamping of
the portal triad and allows tolerance to a prolonged Pringle
manoeuvre, resulting in less hepatic injury and dysfunction
postoperatively,41,42 akin to cardiac pre-conditioning methods.
The precise mechanism of this protection is unknown. Possible
pathways involving roles for adenosine, protein kinase C,
tyrosine kinases or nitric oxide have all been hypothesised.43

Features of acute liver failure

Acute liver failure is characterised by a number of biochemical
and haematological abnormalities, and widespread organ
dysfunction.

Biochemistry
By definition, there is non-obstructive jaundice. Liver failure is
commonly associated with a salt/water imbalance due to
reduced renal blood flow and abnormalities that develop
within the renin-angiotensin axis. There is a tendency towards
water retention and hyponatraemia. A metabolic acidosis
often develops in the early stages of acute liver failure. This
can originate from a number of different sources. Lactic acid
is poorly metabolised, inadequate tissue oxygen delivery (or
use) can generate lactic acid, and associated acute kidney
injury results in the presence of other organic acids.
Hypoglycaemia develops from an impaired glycogenolysis and
gluconeogenesis. Other electrolytes (Mg2+, K+, PO43-) are often
deranged and may need replacing.

Haematology
A coagulopathy invariably develops, including potentially low
fibrinogen levels. There is decreased synthesis of clotting
factors V, VII, IX and X that results in prolonged prothrombin
and activated partial thromboplastin times. There will also be
an element of fibrinolysis, such that bleeding can be worse
than anticipated by the laboratory test results. Platelet numbers
are often low, due to consumption within the damaged liver,
and their function often impaired. Haemorrhage can develop
from any site. Brain haemorrhage is a particularly devastating
complication, while gastrointestinal bleeding is perhaps the
most common. It may develop from stress gastritis,
concomitant ulcers, and portal hypertensive gastropathy or
varices, if present.

Insulin therapy

Neurology

Diabetes mellitus alters the immune response to surgery and

increases morbidity and mortality after liver resection.38,39
High-dose insulin, combined with simultaneous preoperative

Encephalopathy, cerebral oedema, intracranial haemorrhage

and seizures are all recognised complications in acute liver
failure. Intracranial haemorrhage should be suspected if

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there are localising signs. Cerebral oedema is a worrying

complication, which is more prevalent the more acute the liver
failure. Increased ammonia may be involved in the
development of cerebral oedema by both cytotoxic and
vasogenic mechanisms.

Cardiovascular
Distributive shock develops with severe peripheral shunting. A
high cardiac output, decreased oxygen extraction, and low
systemic vascular resistance are all features. The origin of the
peripheral shunting is unclear. It may be the result of
platelet/fibrin plugs, and abnormal vasomotor tone.44 The
result is poor peripheral extraction of oxygen.

Renal
Acute kidney injury is common. This is multifactorial; the
common reasons are pre-renal renal failure and acute tubular
necrosis. Hepato-renal syndrome (HRS) can occur in fulminant
liver failure and is associated with high morbidity and
mortality.45 HRS is more typically associated with
decompensated chronic liver disease, portal hypertension and
spontaneous bacterial peritonitis. Differentiating HRS from prerenal failure that progresses to ATN can be difficult. Urine
sodium analysis and microscopy can be helpful. HRS typically
takes longer to resolve, if it does at all, being associated with
greater than 50% mortality. When acute liver failure develops
following a resection, it will be acute (within 28 days),
so manifestations more commonly linked to chronic liver
disease are less likely to be present, such as portal hypertension
and tense ascites. However, if they occur (as the underlying
architecture of the remaining liver may be compromised)
then they should be managed appropriately. If tense ascites
is present, then reducing intra-abdominal pressure can
improve renal function. Hypophosphataemia can also
sometimes be seen after liver resection due to increased renal
excretion of phosphate.

Infection
Immunocompromise is a feature of acute liver failure12 and
consequently bacterial and fungal infections are more
prevalent. Infection can also be harder to detect as there
is a blunted systemic inflammatory response in this population.
A high index of suspicion is required; for management,
see below.

Pharmacology
A number of drugs are metabolised in the liver. This results in
prolonged effects of sedation, certain neuromuscular blockers
and a number of housekeeping ICU drugs, eg omeprazole.

Supportive management of acute liver failure

In most centres, patients undergoing liver resection will be
admitted to a level 2 bed for initial postoperative care. The
majority of patients will pass through without complication. If
acute liver failure develops, then supportive management
(Table 3) is required until either the liver regenerates, a
treatable cause of the liver failure is established or (if
appropriate) an orthotic liver transplant is performed.
136

Airway
Intubation will be required when the airway is no longer
protected in grade 3/4 encephalopathy, or if the airway is
compromised in another way.

Respiratory
Hypoxia may be a problem due to concomitant pneumonia,
pulmonary oedema or pulmonary haemorrhage. Due to the
concern over the possibility of cerebral oedema, PaCO2 will
have to be controlled tightly at 4.5-5 kPa and minimal
achievable PEEP should be used.

Cardiovascular
Distributive shock usually develops and appropriate fluid
loading and vasopressors will be needed. A cerebral perfusion
pressure of 50-60 mm Hg will be required for neuroprotection.

Neurological
As previously stated, encephalopathy, cerebral oedema,
intracranial haemorrhage and seizures can occur. In acute liver
failure, the level of encephalopathy and degree of oedema are
closely linked. If cerebral oedema is suspected, neuroprotective
strategies should be implemented such as the aforementioned
control of carbon dioxide levels and arterial blood pressure
control. Other aspects include maintaining blood sugar levels
of less than 10 mmol/L (avoiding hypoglycaemia), keeping the
head up at 30 degrees and avoiding ties for the endotracheal
tube. An intracranial pressure monitor may be inserted;
however, risks of intracranial bleeding and infection are higher
in the liver failure population. It can be a useful monitor
provided that it is used to guide use of aggressive therapy, such
as hypertonic saline to achieve a sodium level of 145155 mmol/L, mannitol, cooling to 32-34 degrees or deep
sedation to achieve burst suppression. Other monitors can also
be used, such as the transcranial Doppler or jugular bulb
oxygen saturation monitor, to guide therapy. Encephalopathy is
typically graded from 0 to 4, and is thought to result from a
number of metabolites not cleared by the liver; this improves
as liver function returns. Administration of regular lactulose
may be helpful. Seizures should be initially controlled with
phenytoin and minimal doses of benzodiazepines (due to their
prolonged action). An electroencephalogram may be required
to prove termination of seizures if any doubt exists. The cause
for the seizures should be established, including brain imaging.

Biochemistry
Bicarbonate infusions can be used, but often, renal replacement
therapy is required to provide the appropriate support for
acidosis, fluid and electrolyte control. Anticoagulation of the
filter circuit may not be required or, depending on the platelet
count, prostacyclin may be used.

Coagulopathy
In the early postoperative period, it is reasonable to treat an
INR of >1.5. However, others suggest that it is not necessary to
correct clotting abnormalities (provided there is no bleeding)
unless invasive procedures are planned or the coagulopathy is
profound.2 In fulminant liver failure, coagulopathy can be
profound (and resistant to Vitamin K). In this unit, we correct
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Problem

Management/Aim

Circulatory disturbances

CVP 8-12 mm Hg
MAP 65-90 mm Hg
Haematocrit 30%
Central venous oxygen saturation 70%

Respiratory dysfunction

Arterial oxygen saturation 93%

Renal dysfunction

Urine output 0.5 mL/kg/hr

Liver protection

N-acetylcysteine infusion for 72 hours: 150 mg/kg loading dose over

one hour, 12.5 mg/kg/hr for four hours, 6.25 mg/kg/hr subsequently

Sepsis

Septic screen: CXR, sputum, urine and blood culture

Ascitic fluid from drain site
Consider CT abdomen
Start antibiotics if worsening of encephalopathy or SIRS parameters

Coagulopathy

Platelet count 50 x 109/L

(correct if bleeding or invasive procedure)

International standardised ratio 1.5

Ascites

Paracentesis if severe pain or respiratory/renal compromise

Encephalopathy/cerebral oedema

Start lactulose

If grade 3-4

Neuroprotective strategies: keep PaO2>10 kPa, PaCO2 4.5-5 kPa,

cerebral perfusion pressure >50-60 mm Hg, blood sugar 6-10 mmol/L,
head up, no neck ties
Consider ICP monitor and/or other cerebral monitoring tools.
Resistant ICP treatments include hypertonic saline, mannitol and
cooling to 32-24C

Nutrition

Enteral energy supply of 2,000 kcal/day

Enteral is preferred to parenteral route
Maintain euglycaemia and other electrolytes within normal
range (K+/PO4-3/Mg++)

Stress ulcer prophylaxis

Start proton pump inhibitor

48

Table 3 Goal directed therapy, adapted from: van den Broek, Hammond.3

the coagulopathy if haemostasis is required or for

interventional procedures. Fresh frozen plasma (FFP) and
cryoprecipitate can be used, but give a significant volume load.
Consequently, recombinant factor VIIa and fibrinogen
concentrate can be useful. Early thrombocytopenia is often not
corrected until levels are below 50 x 109/L and haemostasis is a
concern. Thrombocytopenia that develops later can have lower
limits prior to correction. Platelet dysfunction can be
quantified by using appropriate thrombo-elastogram
preparations or platelet function analysers.

Renal dysfunction
Acute kidney injury should be managed by the three basic
principles:
Providing an adequate blood pressure
Optimal cardiac output with appropriate fluid loading
Avoiding nephrotoxic drugs.
If severe liver failure develops, continuous haemofiltration is
usually required for a number of reasons, most commonly,
profound acidosis. It is not clear whether haemodiafiltration or
high volume exchanges provide any significant survival
JICS Volume 14, Number 2, April 2013

advantage. If HRS is suspected, then there is limited evidence to

suggest that terlipressin is a useful vasopressor and that albumin
is a useful replacement fluid.46 This can be 4.5% albumin if
hypovolaemia is suspected and 20% albumin otherwise.
In the event of tense ascites, drainage should be performed
to prevent a high intra-abdominal pressure, but it is unclear
whether high-volume or low-volume ascites removal (with
appropriate albumin replacement) is beneficial.

Infection
Patients with liver failure are at particular risk of developing
sepsis due to a combination of immunoparesis, poor
nutritional status and increased gut translocation. Sepsis can
arise as a result of both bacterial and fungal pathogens (see
Table 4). Some studies have demonstrated that prophylactic
antibiotics can reduce the incidence of infective complications
in patients with established postoperative liver failure,3,7,47,48
however they are not routinely recommended as they have not
been shown to improve outcomes or survival.3,49,50 Equally,
some studies have suggested a role for routine antifungal
prophylaxis, although conclusive evidence is lacking.51
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Fungal

Bacterial

Candidia albicans

Escherichia coli

Aspergillus

Staphylococcus
Pseudomonas

Table 4 Commonest pathogens in liver failure.52

Diagnosing sepsis in this population is difficult and regular

surveillance cultures are recommended with an early escalation
of antibiotic therapy and antifungals.

Nutrition
Poor nutritional status can affect outcome after major cancer
surgery.53 It is associated with an altered immune response and
can reduce regeneration of liver cells.54-56 Early enteral feeding
can preserve the integrity of the gut barrier and so reduce
postoperative infection rates.57,58 Those developing liver failure
should have regular high-dose lactulose (start at 20 mL tds) to
produce 3-4 soft stools per day.

N-acetylcysteine (NAC)
Glutathione is an anti-oxidant found in the liver and plays an
important role in the cellular defence mechanisms against
oxidative damage from free radicals.59,60 Glutathione is oxidised
by oxygen-free radicals; its oxidised form is then reduced by
NADPH (reduced nicotinamide adenine dinucleotide
phosphate) forming an oxidation/reduction cycle that serves to
mop up harmful free radicals. During hypoxia, glutathione
stores are consumed, which can add to oxidative injury on
reperfusion.61,62 NAC is a precursor to glutathione and, when
given as an infusion postoperatively, may reduce liver
dysfunction. NAC also has an anti-inflammatory action
inhibiting chemotaxis. This, in turn, decreases the generation
of oxygen-free radicals by phagocytic cells.63 In other nonparacetamol-induced causes of acute liver failure, both
intravenous and oral NAC have been shown to improve
transplant-free survival and appear safe and well tolerated.64,65
However, the evidence for the routine use of NAC to reduce
ischaemia/reperfusion injury and prevent complications after
major surgery is inconclusive.62 Many units still use this as a
routine therapy until normal liver function has returned.35

Acute postoperative liver failure amenable to

treatment
It is important to rule out any treatable cause of post-resection
liver failure:
Portal vein thrombosis: This will give rise to ischaemia and
possible infarction. The diagnosis can be made using either
ultrasound Doppler or CT scan. The debate over whether
early postoperative portal vein thrombosis is best managed
with surgical de-obstruction or anticoagulation remains
unresolved.24
Venous outflow obstruction: Where this is due to rotation of
the remnant liver segment, surgical intervention is
indicated. There is also a role for endovascular stenting to
improve venous outflow.66
Small-for-size remnant: There is some evidence that
patients with a small remnant and venous congestion
138

secondary to relative hyperperfusion may be successfully

managed by decreasing portal venous inflow through
embolisation of the splenic artery as described in two case
series.67,68 Surprisingly, neither of these reported any serious
complications such as splenic infarction, but this was not
been replicated in another, smaller case series.69

Liver transplantation
Liver resection is often performed for the removal of metastatic
malignancy and in these circumstances, consideration for liver
transplant is often not appropriate. However, provided there
are no contraindications, liver transplantation can be
considered and has been successfully used as the treatment of
postoperative liver failure.24 The Milan criteria, developed in
patients undergoing resections for hepatocellular carcinoma to
help identify those suitable for transplantation, are as follows:
Single lesion hepatocellular carcinomas of <5 cm or up to
three lesions <3 cm
No extra-hepatic disease
No vascular invasion.70
Van den Broek et al48 suggested that if the patients had
favourable tumour characteristics, they would consider
transplantation. These included an R0 resection (ie complete
resection of tumour), low T (ie small tumour size) and
negative nodal spread.

Novel therapies
Hepatocyte transplantation
Infusion of cryopreserved hepatocyte cells into the hepatic
portal vein has shown encouraging results for genetic,
metabolic liver conditions. Encapsulated hepatocytes have
been transplanted intraperitoneally (thereby avoiding the need
for immunosuppressive therapy) to help treat postoperative
liver failure, but this technology is at an early experimental
stage.71

Ex vivo perfusion using porcine livers

This technique has been used, with limited success.72 In a case
series of four patients, there was an improvement in
biochemical markers, but only one patient stabilised enough to
receive a transplant and proceed to long-term survival.

Extracorporeal hepatic support devices

There are several liver-support devices available, using
albumin-linked
haemodialysis
systems,
eg
MARS,

Prometheus , or SPAD extracorporeal liver-assist devices using

cryopreserved xenogeneic or human hepatocytes. These have
been used as a bridge to transplantation. These devices lead to
an improvement in biochemical numbers but there is no
evidence that they result in clinical improvement.1,48,73 Five
patients with postoperative liver failure received MARS
(Molecular Adsorbant Recirculating System). All showed
improvement in biochemical markers but only one survived.74
A similar but larger case series from Hong Kong showed
similar improvements in biochemical markers and similar poor
outcomes with a 72.2% 30-day mortality.75 MARS uses an
extracorporeal system where blood is dialysed against an
albumin-enriched solution. It is similar to the Prometheus
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system, which also uses the principle of albumin dialysis,

where lipophilic albumin-bound toxins (eg bilirubin, etc) are
filtered and then adsorbed with a second circuit, to clean the
albumin before being returned to the patient. SPAD is a SinglePass Albumin Dialysis system which uses a similar circuit to
MARS, except it uses normal machines and no perfusion
pump systems, and uses a counter-current flow of albumin
solution. Studies have shown that SPAD can achieve greater
clearance of ammonia and bilirubin than MARS, although
clearance of water-soluble substances was similar between the
two methods.76

Conclusion
Despite vast improvements in the perioperative care of patients
undergoing liver resection surgery, there remains a significant
risk of developing postoperative liver failure. Best estimates
place the incidence at about 8%. Preoperative liver function
and resection size are the most important factors in the risk
associated with postoperative liver failure, although a number
of pre- and peri-operative factors are also important, such as
the presence of diabetes mellitus or the use of vaso-occlusive
techniques. With advances in chemotherapy, patients who
traditionally would not have been considered operable are
becoming amenable to surgical treatment. Careful patient
selection and optimisation, for example using portal vein
embolisation, are important in reducing the incidence of
postoperative liver failure.
If acute liver failure occurs, then treatable conditions (such
as segment torsion) should be considered and appropriate
supportive care provided. Preventing and managing
complications (commonly infective or haemorrhagic) are also
an important aspect of care. Fulminant post-resection liver
failure has a very poor prognosis, accounting for the majority
of post-liver resection deaths.

References
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Chris Jones Clinical Research Fellow

drchrisnjones@yahoo.co.uk
Leigh Kelliher Clinical Research Fellow
Colin Bigham Locum Consultant in Anaesthesia and Intensive
Care

Nial Quiney Consultant in Anaesthesia and Intensive Care

Royal Surrey County Hospital NHS Foundation Trust

Volume 14, Number 2, April 2013 JICS