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

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
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 µmol/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,

with the result that bleeding will principally be a result of hepatic venous pressure. A larger remnant volume needs to be 134 present at the end of surgery.6 However those with parenchymal diseases require a larger residual volume (approximately 40%) to avoid postoperative liver failure.5 >3. postoperative liver failure can result from altered vascular supply.1 although others suggest it is nearer 8%. Portal or hepatic vein obstruction can occur either through thrombosis. which itself can be reduced by maintaining a low CVP intraoperatively.3. the Pringle manoeuvre is now used much less frequently26 and for less than forty-five minutes in total during surgery. If the liver remnant is too small. Occasionally an isolated increase in bilirubin can occur. It is worth considering these options and excluding them with an ultrasound scan. for example following a blood transfusion or in a patient with Gilbert’s syndrome. mortality rates following liver resection surgery have decreased from 20% in the 1970s8 to approximately 2% today.20 the relative increase in blood flow causes sinusoidal dilatation. Periods of intraoperative hypoxia.28 diabetes mellitus and poor nutritional status.20 Both sinusoidal injury and steatosis from chemotherapy reduce the regenerative capacity of the liver remnant and therefore increase the likelihood of postoperative failure. a remnant as small as 26% of the original liver’s volume can be safely left.16. or following total parenteral nutrition on the intensive care unit.18 A normal subject with no other risk factors can have up to 75% of their liver resected safely.6. A decreased activity of hepatic glucuronyl transferase leads to an increase in unconjugated bilirubin.20 Underlying liver disease reduces the functional and regenerative capacity of the liver and therefore makes it more susceptible to damage.6 3-4=moderate.5 1. 10% when four segments are being resected and 30% for those having five or more segments resected. haemorrhagic infiltration. erythromycin and NSAIDs). Gilbert’s syndrome is present in 2-5% of the population. Following liver resection. but can occasionally be a result of the surgery itself. Another problem with small liver remnants is hyperperfusion. centrilobar necrosis and prolonged cholestasis. 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). April 2013 JICS . Number 2.’ when dysfunction occurs after a living-donor partial graft. Schindl and colleagues believe that the risk should be quoted as less than 1% in patients with no parenchymal disease and having small resections.5 Encephalopathy severity grade None 1 and 2 3 and 4 Table 2 Severity of postoperative hepatic dysfunction score. It is thought to be due to portal hyperperfusion of the graft.’ It is often drug-induced (eg penicillin. torsion or surgical injury. there may not be enough functioning hepatocytes for adequate synthesis. The incidence of acute liver failure following hepatic resection has been reported to be as high as 32% by some authors.27 Other risk factors for postoperative liver failure include age over sixty-five. intra-operative blood loss of more than one litre with the need for blood transfusion increases the risk of postoperative liver failure and sepsis. as the ability of the liver to regenerate decreases with age.9 Postoperative hepatic insufficiency/failure accounts for between 60 and 100% of these deaths.13-15 Causes of post-hepatic resection liver failure Liver dysfunction is seen occasionally after any major surgery.3.19 The liver has a great capacity to regenerate.12 • The size of resection • Evidence of preoperative liver parenchymal disease (eg cirrhosis) • Hepatic ischaemia/reperfusion injury.18 Being male doubles the risk of developing postoperative liver failure.25 resulting in hepatic ischaemia/reperfusion injury. ie occlusion of hepatic artery and portal vein inflow to the liver.17 Sepsis has a detrimental effect on liver function (by inhibiting Kupffer cell function) and affects hepatic cell regeneration. The most important risk factors for postoperative liver failure are:3. The ‘Pringle’ manoeuvre refers to the total occlusion of inflow. resulting in sinusoidal congestion and endothelial dysfunction.22. excretion and detoxification.23 Sinusoidal injury may also occur as a result from ‘small-for-size syndrome. They found that 50% of patients developed sinusoidal obstruction syndrome and 10% steatohepatitis on histological analysis (5% had both).5. 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. Removal of four or more segments (out of eight) is associated with an increased risk of postoperative liver failure.18 Chemotherapy also affects liver parenchyma and reduces its regenerative capacity. with rates between 15-35%.29 Rarely. This limits blood supply to the liver. combined with poor venous outflow. or total inflow occlusion.3. the generation of free radicals and subsequent liver dysfunction.3.10-12 Morbidity following liver resection remains high. Preventative strategies Careful patient selection to ensure adequate residual liver volume In patients with normal liver parenchyma. Vascular occlusive techniques used to reduce intraoperative bleeding comprise either total occlusion of both inflow and outflow. For this reason. the use of blood transfusions or development of sepsis can all result in liver ischaemia and/or cellular dysfunction.24 A similar picture can be seen after extensive hepatic resection with a small liver remnant. >4= severe dysfunction. hypotension. causing further impaired synthetic function and inhibition of cell proliferation.Review articles Points 0 1 2 Total serum bilirubin (µmol/L) ≤20 21-60 >60 Prothrombin time (seconds above normal) <4 4-6 >6 Serum lactate (mmol/L) ≤1. Occlusion induces ischaemia in the liver remnant. Postoperative cholestasis can also ‘muddy the waters.19 a similar volume has been suggested for those patients who have received intensive chemotherapy treatment Volume 14.6-3.6 With advances in surgical and anaesthetic techniques.

due to consumption within the damaged liver.17 Strategies to reduce blood loss include: maintaining a low central venous pressure (<5 mm Hg). the authors found that residual volumes of 44. 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. It may develop from stress gastritis. while gastrointestinal bleeding is perhaps the most common. which led to higher cell substrate availability. There is decreased synthesis of clotting factors V.21 In that study. Hypoglycaemia develops from an impaired glycogenolysis and gluconeogenesis. Haemorrhage can develop from any site. IL-10.43 Features of acute liver failure Acute liver failure is characterised by a number of biochemical and haematological abnormalities. Haematology A coagulopathy invariably develops. cerebral oedema. In patients with cirrhosis. including potentially low fibrinogen levels. combined with simultaneous preoperative Encephalopathy. the requirement for blood transfusion following major blood loss increases the risk of postoperative liver failure. an ultrasonic system used to dissect liver parenchyma.1% and 37. and portal hypertensive gastropathy or varices. furosemide. The precise mechanism of this protection is unknown. intracranial haemorrhage and seizures are all recognised complications in acute liver failure. The use of halothane. sevoflurane and desflurane. including isoflurane. Minimise blood loss Postoperative blood transfusions have an immunosuppressive effect16 and. (diabetics and non-diabetics). 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. and their function often impaired.7% were independent predictors of overall morbidity.8%.40 Fisette and colleagues used insulin infusions for all patients. TNF-α and CRP) and decreased hepatocellular apoptosis. and associated acute kidney injury results in the presence of other organic acids.16.42 akin to cardiac pre-conditioning methods. only very small resections in selected patients should be offered to patients with Child-Pugh class B. and the use of GTN and remifentanil infusions. Possible pathways involving roles for adenosine. but with the added risk of causing ischaemic damage. Other electrolytes (Mg2+.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. which on repeated exposure may cause hepatitits (so-called ‘halothane hepatitis’) is now uncommon. insulin and dextrose infusions have been used by some as treatment for postoperative liver dysfunction. 43. altered the inflammatory response (decreased cytokines IL-6. there is non-obstructive jaundice. protein kinase C. if present. Ischaemic preconditioning Ischaemic preconditioning involves intermittent clamping of the portal triad and allows tolerance to a prolonged Pringle manoeuvre. inadequate tissue oxygen delivery (or use) can generate lactic acid. have minimal hepatic metabolism and there is a lack of evidence demonstrating hepatotoxicity. but to date there is no evidence to support this. Where an extensive resection is planned. reduce the rates of postoperative liver dysfunction. IX and X that results in prolonged prothrombin and activated partial thromboplastin times. A metabolic acidosis often develops in the early stages of acute liver failure. sepsis and liver failure respectively. resulting in less hepatic injury and dysfunction postoperatively.32 avoidance of excessive PEEP. Surgical use of the Pringle manoeuvre can also be used to prevent blood loss. April 2013 135 . VII. and avoided in class C patients. concomitant ulcers.31 Total intravenous anaesthesia (TIVA) has been advocated by some as a preferred option in liver surgery. performing a staged hepatectomy or a preoperative portal vein embolisation (PVE).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.41. PO43-) are often deranged and may need replacing. Platelet numbers are often low. as stated above. 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. Insulin therapy Neurology Diabetes mellitus alters the immune response to surgery and increases morbidity and mortality after liver resection.39 High-dose insulin. Surgical techniques which can minimise blood loss include the use of the CUSA™ (Cavitron Ultrasonic Surgical Aspirator).38. infections and complications.36 Haemostatic agents have also been used to good effect. which has enough energy to destroy liver parenchyma but not enough to damage vascular structures. and widespread organ dysfunction. For these reasons. Brain haemorrhage is a particularly devastating complication. There will also be an element of fibrinolysis. tyrosine kinases or nitric oxide have all been hypothesised. Number 2. There is a tendency towards water retention and hyponatraemia. the use of thoracic epidurals.40 although there are no randomised controlled trials in this area. Other volatile agents. K+. oral carbohydrate loading and intravenous dextrose infusions.Review articles (>6 cycles) prior to liver resection surgery. Lactic acid is poorly metabolised. such that bleeding can be worse than anticipated by the laboratory test results. This can originate from a number of different sources. It uses ultrasound at approximately 25 kHz. Intracranial haemorrhage should be suspected if JICS Volume 14.37 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. resections should only be offered in those with stable disease (ie Child-Pugh class A). Biochemistry By definition.

Respiratory Hypoxia may be a problem due to concomitant pneumonia. Renal Acute kidney injury is common. being associated with greater than 50% mortality.44 The result is poor peripheral extraction of oxygen. portal hypertension and spontaneous bacterial peritonitis. Neurological As previously stated. depending on the platelet count. Due to the concern over the possibility of cerebral oedema.Review articles there are localising signs. A high index of suspicion is required. Encephalopathy is typically graded from 0 to 4. neuroprotective strategies should be implemented such as the aforementioned control of carbon dioxide levels and arterial blood pressure control. fluid and electrolyte control. risks of intracranial bleeding and infection are higher in the liver failure population. Number 2. this improves as liver function returns. It can be a useful monitor provided that it is used to guide use of aggressive therapy. encephalopathy. Infection Immunocompromise is a feature of acute liver failure12 and consequently bacterial and fungal infections are more prevalent. A cerebral perfusion pressure of 50-60 mm Hg will be required for neuroprotection. which is more prevalent the more acute the liver failure. HRS typically takes longer to resolve. This results in prolonged effects of sedation. including brain imaging. Cerebral oedema is a worrying complication. April 2013 JICS . to guide therapy. see below. The majority of patients will pass through without complication. or if the airway is compromised in another way. Cardiovascular Distributive shock develops with severe peripheral shunting. Anticoagulation of the filter circuit may not be required or. if it does at all. However. However. Biochemistry Bicarbonate infusions can be used. it will be acute (within 28 days).45 HRS is more typically associated with decompensated chronic liver disease. If acute liver failure develops. then reducing intra-abdominal pressure can improve renal function. Seizures should be initially controlled with phenytoin and minimal doses of benzodiazepines (due to their prolonged action). 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. 136 Airway Intubation will be required when the airway is no longer protected in grade 3/4 encephalopathy. the level of encephalopathy and degree of oedema are closely linked. eg omeprazole. a treatable cause of the liver failure is established or (if appropriate) an orthotic liver transplant is performed. An electroencephalogram may be required to prove termination of seizures if any doubt exists. PaCO2 will have to be controlled tightly at 4. Other monitors can also be used. Other aspects include maintaining blood sugar levels of less than 10 mmol/L (avoiding hypoglycaemia). such as hypertonic saline to achieve a sodium level of 145155 mmol/L. however. intracranial haemorrhage and seizures can occur. If cerebral oedema is suspected. pulmonary oedema or pulmonary haemorrhage. and is thought to result from a number of metabolites not cleared by the liver. Coagulopathy In the early postoperative period. it is reasonable to treat an INR of >1. cerebral oedema. In acute liver failure. Urine sodium analysis and microscopy can be helpful. If tense ascites is present. such as the transcranial Doppler or jugular bulb oxygen saturation monitor. Hypophosphataemia can also sometimes be seen after liver resection due to increased renal excretion of phosphate. Infection can also be harder to detect as there is a blunted systemic inflammatory response in this population. A high cardiac output. mannitol. In this unit. renal replacement therapy is required to provide the appropriate support for acidosis. certain neuromuscular blockers and a number of ‘housekeeping’ ICU drugs. then supportive management (Table 3) is required until either the liver regenerates.5-5 kPa and minimal achievable PEEP should be used. if they occur (as the underlying architecture of the remaining liver may be compromised) then they should be managed appropriately. The origin of the peripheral shunting is unclear.5. the common reasons are pre-renal renal failure and acute tubular necrosis. Cardiovascular Distributive shock usually develops and appropriate fluid loading and vasopressors will be needed. This is multifactorial. but often. for management. coagulopathy can be profound (and resistant to Vitamin K). The cause for the seizures should be established. cooling to 32-34 degrees or deep sedation to achieve burst suppression. such as portal hypertension and tense ascites. and low systemic vascular resistance are all features. keeping the head up at 30 degrees and avoiding ties for the endotracheal tube. Hepato-renal syndrome (HRS) can occur in fulminant liver failure and is associated with high morbidity and mortality. Pharmacology A number of drugs are metabolised in the liver. and abnormal vasomotor tone. Differentiating HRS from prerenal failure that progresses to ATN can be difficult. 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. An intracranial pressure monitor may be inserted. prostacyclin may be used. When acute liver failure develops following a resection. It may be the result of platelet/fibrin plugs. we correct Volume 14. Increased ammonia may be involved in the development of cerebral oedema by both cytotoxic and vasogenic mechanisms. decreased oxygen extraction. so manifestations more commonly linked to chronic liver disease are less likely to be present. Administration of regular lactulose may be helpful.2 In fulminant liver failure.

5% albumin if hypovolaemia is suspected and 20% albumin otherwise. Some studies have demonstrated that prophylactic antibiotics can reduce the incidence of infective complications in patients with established postoperative liver failure. continuous haemofiltration is usually required for a number of reasons. 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. although conclusive evidence is lacking. most commonly.5 mL/kg/hr Liver protection N-acetylcysteine infusion for 72 hours: 150 mg/kg loading dose over one hour. Number 2. If HRS is suspected. cerebral perfusion pressure >50-60 mm Hg.3.50 Equally. head up. then there is limited evidence to suggest that terlipressin is a useful vasopressor and that albumin is a useful replacement fluid. poor nutritional status and increased gut translocation.7.5 Ascites Paracentesis if severe pain or respiratory/renal compromise Encephalopathy/cerebral oedema Start lactulose If grade 3-4 Neuroprotective strategies: keep PaO2>10 kPa.Review articles 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 ≥0.46 This can be 4. but it is unclear whether high-volume or low-volume ascites removal (with appropriate albumin replacement) is beneficial.49. blood sugar 6-10 mmol/L.51 137 . some studies have suggested a role for routine antifungal prophylaxis. Infection Patients with liver failure are at particular risk of developing sepsis due to a combination of immunoparesis. mannitol and cooling to 32-24°C Nutrition Enteral energy supply of 2. Early thrombocytopenia is often not corrected until levels are below 50 x 109/L and haemostasis is a concern.48 however they are not routinely recommended as they have not been shown to improve outcomes or survival. 12. profound acidosis.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. Consequently. April 2013 advantage. If severe liver failure develops. Sepsis can arise as a result of both bacterial and fungal pathogens (see Table 4).25 mg/kg/hr subsequently Sepsis Septic screen: CXR. drainage should be performed to prevent a high intra-abdominal pressure. Hammond. Thrombocytopenia that develops later can have lower limits prior to correction. PaCO2 4. but give a significant volume load.3 the coagulopathy if haemostasis is required or for interventional procedures.5-5 kPa. adapted from: van den Broek. 6. In the event of tense ascites. Fresh frozen plasma (FFP) and cryoprecipitate can be used.3. no neck ties Consider ICP monitor and/or other cerebral monitoring tools. Platelet dysfunction can be quantified by using appropriate thrombo-elastogram preparations or platelet function analysers. Resistant ICP treatments include hypertonic saline.5 mg/kg/hr for four hours.47. recombinant factor VIIa and fibrinogen concentrate can be useful. It is not clear whether haemodiafiltration or high volume exchanges provide any significant survival JICS Volume 14. 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. sputum.

using albumin-linked haemodialysis systems.71 Ex vivo perfusion using porcine livers This technique has been used. These included an R0 resection (ie complete resection of tumour). surgical intervention is indicated.75 MARS® uses an extracorporeal system where blood is dialysed against an albumin-enriched solution.54-56 Early enteral feeding can preserve the integrity of the gut barrier and so reduce postoperative infection rates. metabolic liver conditions. which can add to oxidative injury on reperfusion.69 Liver transplantation Liver resection is often performed for the removal of metastatic malignancy and in these circumstances. but this technology is at an early experimental stage. Number 2. 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.67. there was an improvement in biochemical markers.70 Van den Broek et al48 suggested that if the patients had favourable tumour characteristics. but only one patient stabilised enough to receive a transplant and proceed to long-term survival.60 Glutathione is oxidised by oxygen-free radicals. The debate over whether early postoperative portal vein thrombosis is best managed with surgical de-obstruction or anticoagulation remains unresolved.62 NAC is a precursor to glutathione and. glutathione stores are consumed. There is also a role for endovascular stenting to improve venous outflow.52 Diagnosing sepsis in this population is difficult and regular surveillance cultures are recommended with an early escalation of antibiotic therapy and antifungals.64. low T (ie small tumour size) and negative nodal spread.48. provided there are no contraindications. or SPAD extracorporeal liver-assist devices using cryopreserved xenogeneic or human hepatocytes. During hypoxia. The diagnosis can be made using either ultrasound Doppler or CT scan.57.Review articles Fungal Bacterial Candidia albicans Escherichia coli Aspergillus Staphylococcus Pseudomonas Table 4 Commonest pathogens in liver failure. eg MARS®.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.61. liver transplantation can be considered and has been successfully used as the treatment of postoperative liver failure. However.65 However. when given as an infusion postoperatively. are as follows: • Single lesion hepatocellular carcinomas of <5 cm or up to three lesions <3 cm • No extra-hepatic disease • No vascular invasion. may reduce liver dysfunction. they would consider transplantation. All showed improvement in biochemical markers but only one survived. neither of these reported any serious complications such as splenic infarction. It is similar to the Prometheus® Volume 14. Novel therapies Hepatocyte transplantation Infusion of cryopreserved hepatocyte cells into the hepatic portal vein has shown encouraging results for genetic. Extracorporeal hepatic support devices There are several liver-support devices available. ® Prometheus .1.24 The Milan criteria. 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. NAC also has an anti-inflammatory action inhibiting chemotaxis. but this was not been replicated in another.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. This. April 2013 JICS . These devices lead to an improvement in biochemical numbers but there is no evidence that they result in clinical improvement.24 • Venous outflow obstruction: Where this is due to rotation of the remnant liver segment. Encapsulated hepatocytes have been transplanted intraperitoneally (thereby avoiding the need for immunosuppressive therapy) to help treat postoperative liver failure.73 Five patients with postoperative liver failure received MARS® (Molecular Adsorbant Recirculating System).53 It is associated with an altered immune response and can reduce regeneration of liver cells.72 In a case series of four patients. developed in patients undergoing resections for hepatocellular carcinoma to help identify those suitable for transplantation.58 Those developing liver failure should have regular high-dose lactulose (start at 20 mL tds) to produce 3-4 soft stools per day. consideration for liver transplant is often not appropriate.74 A similar but larger case series from Hong Kong showed similar improvements in biochemical markers and similar poor outcomes with a 72. both intravenous and oral NAC have been shown to improve transplant-free survival and appear safe and well tolerated. decreases the generation of oxygen-free radicals by phagocytic cells. with limited success. smaller case series.63 In other nonparacetamol-induced causes of acute liver failure. in turn. 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. These have been used as a bridge to transplantation. Nutrition Poor nutritional status can affect outcome after major cancer surgery.59.68 Surprisingly.2% 30-day mortality.

Reddy SK et al. History of liver surgery.Behrns KE. Schindl M. Schreckenbach T. Wu T et al. although a number of pre. Wang L et al. Ann Surg 2008.Narita M. then treatable conditions (such as segment torsion) should be considered and appropriate supportive care provided. Hepatic steatosis as a potential risk factor for major hepatic resection.Kooby DA. carbon dioxide. Redhead D. Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. 2. Samy TS et al. Girling K. Preoperative liver function and resection size are the most important factors in the risk associated with postoperative liver failure. Belghiti J. Gentner B.237:860-69. Br J Surg 1998.243:1-7. Quiney N et al. Operative mortality. 22. Preoperative portal vein embolization for major liver resection: a meta-analysis. 23. 30. Emond J. Ben-Porat L et al. Neodjuvant treatment before resection of liver metastases. Guha IN. Anderson AJ. With advances in chemotherapy. Case Scenario: postoperative liver failure after liver resection in cirrhotic patient. Posthepatectomy liver failure. Maddern GJ.Jones RM. J Perioper Prac 2011.85:1058-60. Survival and recurrence after neo-adjuvant chemotherapy and liver resection for colorectal metastases – a ten year study.52:715-29. Anesthesiology 2012. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Br J Surg 1992. Nordlinger B. 5.247:49-57. Risk factors for postoperative complications after liver resection.7:1082-88.33: S35-S41. What is critical for liver surgery and partial liver transplantation: size or quality? Hepatol 2010. Foster JH. If acute liver failure occurs. are important in reducing the incidence of postoperative liver failure. 3. Beckingham IJ. Fawcett WJ et al.116:705-11. Worthington TR. Rees M.8:313-27.35:838-43. 9.Iakova P. Qin LX. 19. Stockman J. except it uses normal machines and no perfusion pump systems.141:247-51. Best estimates place the incidence at about 8%. SPAD is a SinglePass Albumin Dialysis system which uses a similar circuit to MARS®. Farges O et al. Fearon K et al. Bechstein WO. Thomas R. JICS Volume 14. Immunol Res 2002.76 Conclusion Despite vast improvements in the perioperative care of patients undergoing liver resection surgery. blood loss and the use of Pringle manoeuvres in 526 consecutive liver resections. Br J Surg 2010. Rahbari NN. Raptis DA et al. 31. J Surg Res 2007. Ishizaki Y. although clearance of water-soluble substances was similar between the two methods. Lobo DN.Sugiyama Y. such as the presence of diabetes mellitus or the use of vaso-occlusive techniques. Glimelius B et al.242:824-29. 6. J Gastrointest Surg 1998. Quiney N. for example using portal vein embolisation.Review articles system. Schroeder RA. Amin-Hashem M et al. there remains a significant risk of developing postoperative liver failure.Mullen JT. Liver resections in Auckland 1998-2001: mortality. Ann Surg 2003.Jones CN. Br J Surg 2011. Prediction. Schwacha MG.Garcea G. Mantz J. Protection of the liver during hepatic surgery. Wendon J. Awad SS. Gut 2006.371:1007-16. Balzan S. Sorbye H. Gunn K et al. Imamura H et al. J Gastrointest Surg 2004. Karanjia ND. Hepatobiliary Pancreat Dis Int 2005. The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection. Ann Surg 2006. References 1.Lordan JT.4:370-74. Moulton CE.and peri-operative factors are also important.Brooks AJ.126:381-87.113:495-506. Dig Surg 2012. 7. Fuchshuber P et al.79:513-16. 10. Arch Surg 1991. Clin Pharmacol Ther 2008. 16. 26. The effect of hepatic vascular inflow occlusion on liver tissue pH. Eur J Surg Oncol 2009. Christiansen PM et al. 28. 21. Edinburgh Liver Surgery and Transplantation Experimental Research Group (eLISTER). Surgery 2011.McCall J. Eur J Surgical Oncol 2008. 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