garcea 2009 liver failure after resection

7/29/2019 Garcea 2009 Liver Failure After Resection

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R E V I E W A R T I C L E

Liver failure after major hepatic resection

Giuseppe Garcea

G. J. Maddern

Received: 17 August 2008 / Accepted: 19 September 2008 / Published online: 26 December 2008

Springer 2008

Abstract

Introduction The consequence of excessive liver resec-tion is the inexorable development of progressive liver

failure characterised by the typical stigmata associated with

this condition, including worsening coagulopathy, hyper-

bilirubinaemia and encephalopathy. The focus of this

review will be to investigate factors contributing to hepa-

tocyte loss and impaired regeneration.

Methods A literature search was undertaken of Pubmed

and related search engines, examining for articles relating

to hepatic failure following major hepatectomy.

Results In spite of improvements in adjuvant chemo-

therapy and increasing surgical confidence and expertise,

the parameters determining how much liver can be resected

have remained largely unchanged. A number of preopera-

tive, intraoperative and post-operative factors all contribute

to the likelihood of liver failure after surgery.

Conclusions Given the magnitude of the surgery, mortal-

ity and morbidity rates are extremely good. Careful patient

selection and preservation of an obligate volume of remnant

liver is essential. Modifiable causes of hepatic failure

include avoidance of sepsis, drainage of cholestasis with

restoration of enteric bile salts and judicious use of portal

triad inflow occlusion intra-operatively. Avoidance of post-

operative sepsis is most likely to be achieved by patient

selection, meticulous intra-operative technique and post-

operative care. Modulation of portal vein pressures post-

operatively may further help reduce the risk of liver failure.

Keywords Liver failure Liver resection

Introduction

Liver resection is the accepted gold standard of treatment for

liver tumours. Unfortunately, only 1020% of patients with

colorectal liver metastases are candidates for hepatic resec-

tion [1]. The resectability rate for hepatocellular carcinoma is

about 2030% in normal livers, but reduced in patients with

cirrhotic liver [2, 3]. Hence, in any cohort of patients with

primary or secondary tumours, most will be unsuitable for

curative resection due to the presence of extrahepatic disease,

anatomical distribution of their lesions or tumour burden.

The aim of liver resection is to remove all macroscopic

disease (with negative resection margins) and leave sufficient

functioning liver [4] with preservation of vascular inflow and

outflow. The acceptable residual functioning volume should

be approximately 20% of the standard liver volume or the

equivalent of a minimum of two segments [4]. In patients

without normal liver parenchyma, this obligate functional

volume has been estimated to range from 30 to 60% in

patients with chemotherapy steatosis or hepatitis, and from

40 to 70% in cases of cirrhosis [5]. In spite of improvements

in adjuvant chemotherapy and increasing surgical confidence

and expertise, the parameters determining how much liver

can be resected have remained largely unchanged.

Liver failure

The consequence of excessive liver resection is the inexora-

ble development of progressive liver failure characterised by

the typical stigmata associated with this condition, including

worsening coagulopathy, hyperbilirubinaemia and encepha-

lopathy. This rarely occurs in isolation and is often coupled

with failure of multiple organs and/or features of sepsis.

G. Garcea (&) G. J. Maddern

Department of Hepatobiliary and Upper Gastrointestinal

Surgery, The Queen Elizabeth Hospital, 28 Woodville Road,

Adelaide, SA 5011, Australia

e-mail: [email protected]

123

J Hepatobiliary Pancreat Surg (2009) 16:145155

DOI 10.1007/s00534-008-0017-y


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Whilst fulminant liver failure is probably easily diagnosed,

the true contribution of milder forms of liver dysfunction to

mortality post-operatively may be harder to assess and

accurately quantify. Clinically, a mild derangement in liver

function is very common after extended liver resection and

generally resolves within 6 or 7 days postoperatively. Lack of

resolution of this mild dysfunction may herald the insidious

onset of liver failure. Attempts to classify histological chan-ges following surgery-induced hepatic failure have revealed

interesting results, albeit from a small number of patients

(n = 7) [6]. From these clinical findings, liver failure could

be defined as either cholestatic (characterised by regener-

ation of hepatocytes and fibrosis) or nonregenerative

(characterised by pronounced apoptosis of hepatocytes) [6].

The incidence of liver failure after major hepatic resection

ranges from 0 to 30%; however, the lack of a standardised

definition of liver failure makes comparison of reported

incidence between centres difficult [7]. Liver failure would

appear to be a major contributor to post-operative mortality,

being implicated in 1875% of cases [810].

Liver regeneration and liver failure

Normal mechanism of liver regeneration

The liver is unique amongst all other body organs in its

ability to regenerate fully after extensive liver damage,

either due to resection or secondary to drug-induced/viral-

induced damage. Following partial hepatectomy, 95% of thenormally quiescent liver cells re-enter the cell cycle, with an

increase in DNA synthesis that peaks at 24 h following

injury [11]. Induction of DNA synthesis in other liver cells

occurs later, at 48 h for Kupffer and stellate cells and 96 h

for endothelial cells [11]. Clinical studies suggest that

regeneration is evident within 2 weeks following resection

and is complete at 3 months following resection [12, 13].

Hepatocyte activation requires their priming by

inflammatory cytokines, such as interleukin 6 (IL-6) and

tumour necrosis factor alpha (TNF-a) (Fig. 1). These

cytokines are released by Kupffer cells in response to portal-

system-carried factors such as lipopolysaccharide (LPS).

Fig. 1 Overview of the mechanism of liver regeneration following hepatectomy

146 J Hepatobiliary Pancreat Surg (2009) 16:145155

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Once primed, hepatocytes respond to a number of growth

factors including hepatocyte growth factor (HGF) released

by stellate cells. HGF release by stellate cells occurs by

cleavage of pro-HGF by proteases such as urokinase-type

plasminogen activator (uPA). In addition, other trophic

factors from different sources (Fig. 1) also act on the primed

hepatocytes, moving them from G0 to S-phases of the cell

cycle. IL-6, if administered in adequate concentrations, candirectly stimulate hepatocyte proliferation, even in the

absence of other growth factors [14]. The synthesis of

transforming growth factor beta (TGF-b) (which acts in an

inhibitory fashion on hepatocyte proliferation) is blocked in

the early stages of hepatocyte proliferation, but is eventually

restored, bringing an end to hepatocyte regeneration [14].

In addition to promoting cell growth, the cytokine

pathway (specifically the production of IL-6) also inhibits

liver apoptosis (Fig. 1), thus further protecting the post-

operative liver. Inducible nitric oxide is released by hepa-

tocytes in response to cytokine release from Kupffer cells

and may act in suppressing the inhibition of HGF-inducedcyclin D1 and D2 expression [15]. In iNOS gene knockout

murine models, hepatectomy has been found to result in

hepatic failure characterised by marked apoptosis of

hepatocytes [16]. Re-establishment of normal liver archi-

tecture is achieved by stellate cells, in conjunction with

proteins such as connexin-32 and keratin-8, which are

involved in the production of an extra-cellular matrix

approximately 4 days following liver damage [11].

Correlation between liver regeneration and the failing

liver

If enough viable liver remains to support bodily functions

post-operatively, then regeneration (or the lack of it) should

not have an impact on subsequent function of the organ.

However, this would not be the case in the present under-

standing of liver failure following hepatectomy, where a

lack of liver regeneration is frequently linked with the

development of liver failure. This finding could be explained

by postulating that the 20% rule, defining the obligate

mass of liver tissue remaining post-hepatectomy, is depen-

dent on liver regeneration in order to preserve long-term

homeostatic function. Alternatively, the lack of regeneration

found in failing livers may be an index of excessive resection

rather than a contributory cause of failure.

On-going loss of hepatocytes as a consequence of surgery

may mean liver regeneration is essential in order to continue

metabolic activity, in spite of the initial volume of liver

remnant being adequate. As will be discussed subsequently in

this review, physiological and blood-flow-related changes

contribute to post-hepatectomy hepatocyte loss, which may

be exacerbated by other factors such as sepsis. Marked

apoptosis has been described following hepatectomy in

animal models, further contributing to hepatocyte loss [17].

The disturbance of this balance between immediate/on-going

hepatocyte loss and replacement explains the insidious nature

of evolving liver failure following major hepatectomy.

Hence, once the initial liver injury (i.e. resection) has been

sustained, the subsequent recovery of liver function is

dependent on a number of patient-related operative and post-

operative factors (Fig. 2). The focus of this review will be toinvestigate factors contributing to hepatocyte loss and

impaired regeneration in patients undergoing hepatectomy

and how a better understanding of this interplay can be used

to optimise outcome after extended liver resection.

Energy charge following hepatic resection

Failure to regenerate occurs once the remnant volume of liver

falls below a certain threshold. The rate of hepatic metabo-

lism, or the so-called energy charge, has been shown to

decrease following partial hepatectomy [18]. The energycharge also relates to the volume of remaining liver, and once

a certain threshold of volume is reached, regeneration ceases

as the energy demands of other metabolic process (such as

gluconeogenesis) take precedence [19]. Arterial ketone body

ratio offers an index of the mitochondrial adenylate charge of

the liver, and this has been used to predict the prognosis of

patients undergoing hepatic resection [20, 21]. Preservation

of energy metabolism has been shown to increase survival

probability in small-for-size liver grafts and following

hepatectomy in animal models [2224].

Preserving liver remnant may be achieved by selective

portal vein embolisation to the segments of liver planned

for resection, resulting in hypertrophy of the future remnant

liver volume. Portal vein embolisation may be achieved

preoperatively using radiological means or as part of a

staged liver resection. Portal vein embolisation has been

shown to increase liver volume by 816%, although this

increase is dependent on underlying liver function [2528].

Two-stage liver resection involves removing disease from

one lobe, allowing the liver to regenerate, and then

undertaking a second resection to clear any remaining

disease. In this manner, the critical threshold for obligate

remaining liver is never reached. Unfortunately, disease

progression between intervening resections is a significant

risk and has been reported to be as high 46.7% [28].

Haemodynamics following hepatectomy

Normal liver flow

The liver receives a dual blood supply from both the

hepatic artery and the portal vein, with the contribution of

J Hepatobiliary Pancreat Surg (2009) 16:145155 147

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blood flow being widely accepted as 20 and 80% respec-

tively. Following portal vein embolisation, a phenomenon

known as the hepatic arterial buffer response results in

an increased arterial flow to the embolised and non-em-

bolised lobe (due to an adenosine-mediated response

system) [29]. Since the return from the distal portal cir-

culation is unchanged and more blood flow is now

channeled down the remaining portal vein branch, flow tothe non-embolised lobe also increases [30] (Fig. 3).

Portal flow following hepatectomy

Following hepatectomy, the reduction in liver size, and as a

consequence, vascular capacity, result in a marked

decrease in portal vein flow, an increase in hepatic artery

resistance and an increase in portal vein pressure [31]. The

subsequent increase in shear stress in liver sinusoids is an

important initiating factor in liver regeneration and like-

wise a reduction in shear stress may contribute to liver

atrophy [32, 33]. Hepatocytes are surrounded by a three-

dimensional network of vessels which are fenestrated (the

liver sieve) and thus are directly exposed to portal pressure

via these sieve plates. The lack of hepatocyte regeneration

in patients with portal hypertension would seem at odds

with this model of shear stress. This could be explained by

the loss of sieve plates in cirrhotic patients blocking

the stimulus of raised portal pressure on hepatocytes [32]

or by excessive fibrosis limiting the regeneration of hepa-

tocytes [32].

Shear stress and liver damage

Whilst shear stress is an important component of liver

regeneration, excessive pressures may result in microcir-

culatory collapse and subsequent hepatocyte necrosis.

These changes are frequently found with hepatectomies

involving resection of up to 90% of liver [34]. The

reduction in portal vein flow accompanying the dramaticrise in portal pressure further contributes to reduced

regeneration. These observations have been reported in

small-for-size liver transplants where severe ischaemic

changes with sinusoidal congestion have been found in

association with increased portal vein pressure [3537].

Attempts at reducing portal vein pressure have included

portal-systemic shunts and splenectomy [38]. Control of

portal pressure has been shown to improve the survival of

small-for-size grafts in a number of studies [3941]. In

animal models of partial hepatectomy, porto-caval shunting

has resulted in a reduced rate of hepatic necrosis and

reduced apoptotic index in the shunted animals [42, 43]. Inspite of these encouraging results, a marked delay in liver

regeneration has also been reported to be associated with

porto-caval shunts [42, 44]. This could be explained by an

over-reduction of portal shear stress or by diversion of

hepatotrophic factors into the systemic circulation as a

consequence systemic shunting. As discussed previously,

important trophic factors are carried in the portal circula-

tion, which are also required for liver regeneration

following hepatectomy. Liver atrophy is a well-recognised

Fig. 2 Interplay of patient-

related intraoperative and post-

operative factors in the

development of liver failure

post-hepatectomy


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complication of porto-systemic shunting, in cirrhotic livers

at least, and may limit the use of such shunts outside of an

experimental setting. There is, however, animal model

evidence of non-portal growth factors influencing liver

regeneration [45] and of complete liver regeneration being

possible, even with porto-caval shunting [46]. In addition,

the use of mesocaval shunts may be a satisfactory com-

promise by reducing excessive shear stress, whilst

maintaining gastroduodenosplenopancreatic venous return

to the liver and thus preserving hepatotrophic inflow [47].

Alternatively, pharmacological control of portal pressure

may provide short-term post-operative control of portal

pressure in major hepatectomies, which can be ceased

when necessary to allow normal regeneration subsequently.

Intraoperative and post-operative ischaemia

A variety of techniques have been adopted during liver

resection to help reduce the degree of blood loss intraop-

eratively. The Pringle manoeuvre has been widely adopted

and involves clamping the hepatic inflow usually inter-

mittently or up to 1 h continuously. Although blood loss

has been shown to be reduced by this method [48],

bleeding may still occur from the hepatic veins, and for this

reason, some centers have advocated total vascular exclu-

sion of the liver (clamping of the supra and infra hepatic

inferior vena cava coupled with Pringle occlusion) during

resection to create a completely bloodless field. The liver

appears remarkably tolerant to even prolonged periods of

ischaemia, and for the most part, neither the Pringle nor

total vascular exclusion (TVE) appears to cause any per-

manent damage to hepatic tissue, with any histological

changes observed rapidly reversing on re-perfusion [49].

Ischaemic reperfusion has been advocated as a means of

reducing the deleterious effect of ischaemia reperfusion on

the liver. This involves a short period of ischaemia (usually

about 5 min) followed by up to 30 min of reperfusion.

Following this, Pringle clamping can be employed either

continuously or in intermittent cycles. Ischaemic precon-

ditioning (IP) has been shown to decrease the severity of

liver necrosis [50], exhibit an anti-apoptotic effect [51],

Fig. 3 Normal hepatic inflow, demonstrating the hepatic arterial buffer response (figure adapted from Ref. [103])


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preserve liver microcirculation [52], and improve survival

rates following hepatectomy [53]. More recently IP has

been described as promoting liver regeneration via the up-

regulation of cytokines such as TNF-a and IL-6, and the

down-regulation of TGF-b [54].

For liver resections of the magnitude where liver failure

post-operatively is a significant risk, the impact of IP may

not be as beneficial. There is evidence that in animalsundergoing 90% hepatectomy, IP may serve to impair liver

regeneration [55]. In addition, a number of deleterious

effects have been associated with hepatic inflow occlusion

including bacterial translocation of gut organisms and

elevated endotoxins in the portal system [56]. As will be

discussed in the following section, bacteraemia together

with associated sepsis is a frequent association with post-

operative liver failure and prolonged inflow occlusion may

exacerbate this. Finally, prolonged hypotension can

adversely affect liver function, as evidenced by necrosis,

bile plugging and inflammatory cell infiltrates in conjunc-

tion with hyperbilirubinaemia [57]. Post-operative hypo-tension (whether due to bleeding, sepsis or increased

inotropic requirements) may significantly prolong hepatic

ischaemia, especially when prolonged Pringle clamping has

been applied, and result in post-operative liver failure. Thus,

although TVE and Pringle clamping are relatively safe to

employ, their use may combine with other factors also

contributing to liver hypoperfusion, resulting in significant

liver dysfunction. This may only be partially ameliorated by

IP in the context of extended hepatectomies (Fig. 4).

Sepsis

Sepsis affects post-operative liver function and regenera-

tion in a number of different ways. Sepsis is an important

cause of post-operative hypotension and in this manner

may prolong hepatic ischaemia following surgery (see

above). In addition, sepsis adversely affects Kupffer cellfunction, may increase the concentration of liver-toxic

cytokines, and endotoxins released by bacteria have a

direct inhibitory action on hepatocyte proliferation (Fig. 5).

This complex interplay between sepsis and liver regener-

ation explains the frequent association of sepsis with liver

failure in post-hepatectomy patients.

Sepsis and Kupffer cell function

Kupffer cell activation is an important component in the

early initiation of liver regeneration. Leukocyte-Kupffer

cell interaction is thought to trigger a local inflammatoryresponse leading to release of TNF-a and IL-6 which then

act on hepatocytes leading to proliferation [58]. This

interaction is thought to be mediated by an intracellular

adhesion molecule known as ICAM-1, and ICAM-1-defi-

cient mice exhibit impaired liver regeneration with a

concomitant decrease in TNF-a and IL-6 concentrations,

following 70% hepatectomy [58]. The complement cascade

is pivotal to this regeneration pathway [59]. Administration

of endotoxin to hepatectomised rats results in massive

necrosis and up to 50% mortality [60], possibly by interfering

with Kupffer cell activation, either via the complement

pathway or Kupffer cell-leukocyte interaction.

Following large volume hepatectomy, Kupffer cell

numbers are reduced and hence the rapid clearance of

bacteria from blood (one of the predominant roles of

Kupffer cells) is diminished. Dysfunction of Kupffer cell

activity may persist for up 2 weeks following hepatec-

tomy [61]. As a result, impaired clearance of blood-borne

enteric bacteria and their associated endotoxins make

hepatectomised animal models prone to the rapid devel-

opment of multi-organ failure in the presence of sepsisFig. 4 Shear stress and hepatocyte regeneration

Fig. 5 Effect of sepsis on liver function and regeneration after

hepatectomy


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[62]. Translocation of enteric organisms following hepa-

tectomy is well documented and the application of Pringle

clamping may be, in part, responsible [56]. As a result,

hepatectomy results in a proclivity for rapid, over-

whelming sepsis leading to multi-organ failure, whilst in

turn, sepsis acts to diminish the regenerative ability of the

liver.

Sepsis and circulating TNF-a

One of the earliest TNF-a mediated event within hepato-

cytes is activation of NF-kappaB (the main gateway to pro-

inflammatory cytokine pathways). In addition to exerting a

proliferative effect on hepatocytes, NF-kappaB may also

induce apoptosis [63]. In the context of liver resection, the

proliferative pathway appears to predominate [63].

Excessive circulating levels of TNF-a after massive hepa-

tectomy may contribute to liver failure and death, and

suppression of TNF-a has been shown to improve survival

[64]. Sepsis is a further stimulus for elevation of TNF-a,and whilst not yet proven, this may serve as a further

mechanism contributing to on-going liver damage and

inhibition of liver regeneration.

Endotoxins and hepatocytes

Endotoxin release from blood-borne bacteria appears to

have a direct action on hepatocytes resulting in decreased

mitochondrial function and impaired bile salt excretion

[6567]. These effects appear to be mediated indepen-

dently of changes in cardiovascular status. Endotoxin

treatment has been found to inhibit liver regeneration by

suppression of proliferative inhibitory pathways via up-

regulation of TGF-b [67], leading to hepatocyte apoptosis

and perisinusoidal fibrosis [68].

Cholestasis

Obstructive jaundice is a ubiquitous presenting sign in

patients with hilar cholangiocarcinomas. Preoperative bil-

iary drainage of the future liver remnant has been

advocated by some centres in order to optimise patients

prior to surgery [69]. However, major hepatectomy in the

absence of preoperative drainage has been described with

acceptable mortality rates [70]. Drainage may comprise

internal stenting using a plastic endoprosthesis (with sub-

sequent inflammatory changes making hilar dissection and

delineation between normal and malignant tissue prob-

lematic) or external biliary drainage, with diversion of bile

flow extra-hepatically. Cholestasis and diversion of biliary

flow present particular problems and risks in patients fac-

ing major hepatectomies (Fig. 6).

Cholestasis and restricted portal venous flow

The portal vein, hepatic artery and bile duct are enclosed ina sheath of tissue known as the Glissonian capsule, with a

limited amount of space within called the space of Mall

(Fig. 3). Dilatation of the biliary tract reduces the volume

within this space leading to reduction in portal venous flow,

accompanied by an increase in hepatic arterial flow

(hepatic buffer response) [71]. The reduction in portal

venous flow is further exacerbated by hepatectomy, which

may contribute to impaired regeneration post-surgery. In

addition, portal-systemic shunting accompanying obstruc-

tive jaundice may further reduce portal venous flow [72].

Impaired liver regeneration and induction of apoptosis

Hepatectomy in the presence of cholestasis has been found

to significantly inhibit liver regeneration and the expression

of c-myc, which normally precedes the first wave of

mitosis [73, 74], and to decrease the expression of tran-

scription factors involved in hepatocyte proliferation such

as cyclin E [74]. Other liver-regeneration cytokines, such

as epidermal growth factor and IL-6, are also depressed

following hepatectomy in animal models with obstructive

jaundice [72, 75, 76]. High levels of bile salts are associ-

ated with increased hepatocyte apoptosis [77], possibly via

a FAS-dependent mechanism [78].

Interruption of enterohepatic circulation

Bile salts within the small bowel lumen have an important

function in maintaining bowel integrity and prevention of

bacterial translocation [79]. In the presence of obstructive

jaundice, the normal enterohepatic circulation is interrupted

and so portal bacteraemia may be present, increasing

the risk of septic complications following hepatectomy.

Fig. 6 Effect of cholestasis on liver function and regeneration


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Supplementation with bile salts has been show to improve

intestinal barrier function [80]. External biliary drainage

(whilst reducing blood levels of bilirubin) still results in

diversion of bile salts outside of the gut lumen and this may

account for reduced liver regeneration in rats undergoing

hepatectomy with external drains [81]. Liver regeneration

has been found to be preserved with internal drainage [82]

which therefore may be preferable to external drainage.However, in the context of hilar malignancies (where

multiple biliary drainages may be required) endoscopic

internal drainage can be difficult and carries with it a risk of

cholangitis [83]. In addition, internal endoprostheses serve

to increase the technical difficulty of resection. For this

reason, external biliary drainage is often preferred, but the

addition of bile replacement agents may help restore gut

immunity [83].

Cirrhosis, steatosis and the post-chemotherapy liver

Patients with liver cirrhosis have an increased risk of

mortality following resection, with some series reporting

the risk to be as high as 20% [84]. In addition to an overall

operative risk, cirrhosis results in a higher probability of

liver failure and is associated with reduced regeneration

following hepatectomy. Cirrhotic livers demonstrate lower

levels of hepatocyte growth factor (due to a failure of

conversion of the precursor to the active form) [85] and

impaired transcription factors [86] leading to a reduction of

DNA synthesis and lower volumes of regenerated liver

[87]. Cirrhotic livers show an increased risk of ischaemia-

reperfusion injury, and hyperbaric oxygen administration

following hepatectomy has demonstrated some value in

augmenting liver function and regeneration post-hepatec-

tomy [88]. Fibrosis leading to regional ischaemia is also

thought to contribute to impaired growth and regeneration

[89]. Exogenous administration of IL-6 and hepatocyte

growth factor have been shown in animal models to inde-

pendently improve survival and regeneration after surgery

[87, 90]. Attempts to predict which cirrhotic patients are at

greater risk of fulminant liver failure after hepatectomy

have included the Child-Pugh classification system and

functional assessment of liver-related clearance of quanti-

fiable materials such as indocyanine green, hayaluronic

acid or hepatic 99 mTc-diethylenetriamine pentaacetic

acid-galactosyl-human serum albumin [9193].

Steatosis of the liver is an increasingly common finding

either due to life-style related factors or as a common

sequel to chemotherapy for colorectal liver metastases.

Steatosis is associated with a delay in regeneration,

increased susceptibility to ischaemia/reperfusion injury and

increased risk of trauma and bleeding following hepatec-

tomy [9496]. Chemotherapy agents, such as oxaliplatin,

have been found to lead to severe sinusoidal dilatation and

fibrosis in livers of some patients, which may further

increase the risk of hepatic failure in these individuals

undergoing resection surgery [97].

Age and other co-morbidities

A number of patient-related factors contribute to an

increased probability of hepatic failure following hepa-

tectomy. Determining their liver-specific contribution to

mortality and liver dysfunction is problematic. Liver

function appears to be well maintained even at extremes of

age [98], however, some evidence exists that age influences

restoration of liver volume after hepatectomy in rats [99,

100], and in humans, an age of above 50 was found to

negatively influence transplanted liver volumes [101].

Likewise, diabetes has been associated with a greater risk

of mortality from liver failure following liver surgery, and

this could be secondary to the presence of steatotic liver in

these individuals [102]. Given the complex interaction

between factors contributing to liver failure after hepatec-

tomy, it is likely that careful attention to co-morbidities

with subsequent optimisation of patients is an important

component in planning and undertaking major liver

resections.

Conclusion

Major liver resections have now become the accepted goldstandard of treatment for a wide range of primary and

secondary liver malignancies. Given the magnitude of the

surgery, mortality and morbidity rates are extremely good;

however, a small but significant number of individuals will

succumb to liver failure in the immediate post-operative

period. Careful patient selection and preservation of an

obligate volume of remnant liver is essential. Modifiable

causes of hepatic failure include avoidance of sepsis,

drainage of cholestasis with restoration of enteric bile salts

and judicious use of portal triad inflow occlusion intraop-

eratively. Avoidance of post-operative sepsis is most likely

to be achieved by patient selection, meticulous intra-operative technique and post-operative care. Modulation of

portal vein pressures post-operatively may further help

reduce the risk of liver failure.

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