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Chapter 8
Diagnosis of cirrhosis
Repeat endoscopy
patient choice is endoscopic band ligation
Endoscopic band ligation
with ‘red signs’ on endoscopy, the use of non-selective
beta-blockers or EBL is appropriate irrespective
of the severity of liver disease. Pharmacological
treatment with propranolol is first-line option in
these guidelines, with EBL utilised in those with a
contraindication or intolerance to beta-blockers,
taking into account the preferences of the patient.
If a beta-blocker is started there is no indication to
repeat endoscopy.14 Due to cost and risk of sedation,
the AASLD offers pragmatic advice that endoscopy
can be avoided in patients who are already taking
non-selective beta-blockers for other reasons at the
time of their diagnosis of cirrhosis.
9
Once prophylactic therapy is commenced it should
be continued indefinitely, although it is suggested
that beta-blockers are discontinued at the time of
spontaneous bacterial peritonitis, renal impairment
and hypotension.
On cessation of treatment, the patient assumes
the same bleeding risk as untreated patients (25%),
and there may also be an associated increased risk
of mortality over untreated patients in those who
withdraw from treatment.
14,68
69
It has been suggested that EBL may be preferred
for large varices, with high-risk stigmata (e.g. red
wale marks), and Child–Pugh B and C cirrhosis.16 If
EBL is selected, it should be repeated every couple
of weeks until obliteration of varices is confirmed
with follow-up endoscopy repeated for assessment
of recurrent disease.
sclerotherapy are not recommended treatments for
primary prophylaxis of variceal bleeding.
9,70
Nitrates, TIPSS and
9,14,16
An
algorithm for the primary prevention of variceal
bleeding is provided in
Fig.8.3.
Treatment for bleeding varices
As is the case with all major upper gastrointestinal
bleeds, the initial concern in the management of
acute variceal bleeding should be airway protection,
with a low threshold for endotracheal intubation
if required. Resuscitation should be undertaken
in a high-dependency or intensive care unit with
appropriate blood products according to local
protocols, correction of coagulopathy, prophylactic
antibiotics and vasoactive agents (terlipressin or
somatostatin).
considered first-line treatment for the management
of acute variceal haemorrhage since guidelines were
released in 1995 and should be offered to unstable
patients immediately after resuscitation and within
24 hours in all other stable patients.
therapy is successful in 80–85% of patients.
In the event of failure of first-line endoscopic
therapy or if a second re-bleeding event occurs, a
further endoscopy can be considered but guidelines
from the AASLD suggest that an alternative
treatment modality should be attempted next.
If bleeding is difficult to control, an oral-gastric
tube should be inserted until further endoscopic
treatment, TIPSS or (less frequently) surgery can
be undertaken depending on local resources and
expertise.
this time and transfer to a specialist centre that
provides a 24-hour emergency TIPSS service should
be urgently considered.
The delay between the initial bleed and TIPSS
placement, the number of endoscopic attempts and
need for balloon tamponade correlate with increased
mortality when using TIPSS as a rescue therapy.
The strongest predictor of negative outcome is a
HVPG >
14
Endoscopic therapy has been
14,45,71
First-line
72
9,45
14
Specialist input should be sought at
14
44
20 mmHg. Although HVPG measurement
No varices
in 2–3 years*
Figure8.3 • Algorithm for the primary prevention of variceal bleeding. *If there is clear evidence of disease progression
this interval can be adjusted by the treating clinician. Endoscopy should also be offered at time of decompensation.
Grade I varices Grade II or III varices
Repeat endoscopy
in 1 year*
Non-cardio-
selective beta-blocker
(or any varices
with red signs)
Intolerant or contraindication to
non-cardioselective beta-blocker or
142
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Portal hypertension and liver transplantation
is not routinely undertaken in clinical practice, risk
factors suggestive of a HVPG >
20 mmHg include
Child–Pugh C cirrhosis, non-alcohol-related cause
of cirrhosis, systolic blood pressure at the time of
bleeding <
of endoscopy.
100 mmHg or active bleeding at the time
73,74
Initial reports on the use of TIPSS for the management
of recurrent variceal bleeding were favourable with a
92% haemostatic success rate, and an overall 1-year
survival rate of 75–100%, 68–86% and 49–73% for
Child–Pugh A, B and C, respectively.
Two subsequent RCTs have shown that early
TIPSS (within 24–72 hours of admission) compared
with continued medical management including
endoscopic therapy (sclerotherapy or band ligation)
is associated with significant improvement in survival
among high-risk patients (Child–Pugh B patients,
Child–Pugh C patients with a score <14, and those
with HVPG >20 mmHg).
41,77
75,76
After satisfactory haemostasis with first-line
therapy, and depending on local resources, early
TIPSS (<
72 hours after index variceal bleed) can
therefore be considered in selected patients with
Child–Pugh B cirrhosis and active bleeding or
Child–Pugh C cirrhosis with a score <14.
14
Despite the results of these RCTs and subsequent
recommendations, TIPSS is still not considered
a first-line therapy since there is better access to
endoscopy, which is also needed to prove variceal
haemorrhage as the source of gastrointestinal
bleeding. If TIPSS is unavailable or not feasible due
to contraindications, and local expertise permits,
surgical shunting can be considered in Child–Pugh
A patients with minimal comorbidity.
14
Gastric varices
Gastric varices are categorised based on their
relationship with oesophageal varices as well as
their site in the stomach
are considered extensions of oesophageal varices
and should be managed in a similar fashion.
presence of IGV1 should prompt investigation for
the presence of splenic vein thrombosis,
present splenectomy is curative.
of gastric varices is challenging and the threshold to
place a TIPSS for bleeding gastric varices is much
lower compared with oesophageal varices. The
AASLD practice guidelines recommend TIPSS when
cyanoacrylate injection or thrombin are unavailable,
when there is operator unfamiliarity with these
adhesives or in cases of failure of single endoscopic
treatment.
9
Balloon tamponade is suggested as a
temporising treatment for GOV and IGV1 but is
unlikely to be effective for varices more distal in the
stomach.
14
17
(see Table 8.2). GOV1
14
9
78
The management
and if
The
Another viable radiological alternative for nonTIPSS candidates is balloon-occluded retrograde
transvenous obliteration. This procedure involves
insertion of a balloon catheter via the femoral or
internal jugular vein into the spontaneous gastrorenal outflow shunt followed by embolisation of
the veins draining the gastric varices. By blocking
the decompressive gastrorenal shunt the procedure
could aggravate portal hypertension but it may
preserve hepatic function better than TIPSS.
79
It is recommended that patients with GOV1 are
entered into an endoscopic surveillance programme.
Endoscopic surveillance with cyanoacrylate
injection as needed is recommended for GOV2 and
14
An algorithm for the management of acute
IGV.
variceal bleeding is illustrated in
Fig.8.4.
Portal hypertensive gastropathy
Portal hypertensive gastropathy is an abnormality of
the gastric mucosa characterised endoscopically by a
mosaic-like pattern resembling 'snake-skin', with or
without red spots.80 The overall prevalence of portal
hypertensive gastropathy in cirrhosis is roughly
80% and it is strongly correlated with the severity
of cirrhosis.
for treatment of asymptomatic portal hypertensive
gastropathy are lacking.
81
Currently, definitive recommendations
82
During an 18-month
follow-up period, the incidence of acute bleeding was
3%, the bleeding-related mortality rate was 13%
and the incidence of chronic bleeding was 11%.81
Octreotide and terlipressin are advocated for the
treatment of acute bleeding from portal hypertensive
gastropathy based on their ability to decrease portal
blood flow. Non-selective beta-blockers are the
foundation of treatment for chronic bleeding.82
In a previous RCT, propanolol reduced recurrent
bleeding from portal hypertensive gastropathy.
83
Although endoscopy is key in establishing the
diagnosis, the role of endoscopic therapy for portal
hypertensive gastropathy is contentious and its
utility is felt to be minimal due to the diffuse nature
of the bleeding.
80,82,84
When medical management is
unsuccessful, rescue therapy with TIPSS or surgical
shunting may be required. Liver transplantation is a
last resort in cases of refractory bleeding.
82
Segmental portal hypertension
Segmental portal hypertension resulting from splenic
vein thrombosis should always be considered as the
potential cause of bleeding gastric varices in patients
with pancreatic pathology. Those with advanced
malignancy of the pancreas can usually be controlled
with medical management or endoscopic treatment.
Patients with chronic pancreatitis who develop
variceal bleeding as a result of thrombosis of the
splenic vein should be considered for splenectomy,
which is often curative. An alternative option to
splenectomy is splenic artery embolisation.
14
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143
Chapter 8
Upper gastrointestinal bleed in cirrhotic patient
Rescue therapy with TIPSS
prophylaxi
Rescue therapy with TIPSSEarly TIPSS
Resuscitation
Consider intubation, IV access and
activate major haemorrhage protocols
Transfer to HDU or ITU setting
Intravenous antibiotics and vasoactive drugs
Urgent endoscopy
Oesophageal varices Gastric varices
Band ligation
Control of bleeding Continued bleed or re-bleed
Secondary
s
Figure8.4 • Algorithm for the management of acute variceal bleeding.
In Child-Pugh grade B
patients with active bleeding at initial
endoscopy or Child-Pugh grade C
(10–13 points) patients <72 hours
from index bleed
Budd–Chiari syndrome
Budd–Chiari syndrome is an uncommon condition
with an estimated incidence of 0.8 per million per
85
It results from obstruction of venous outflow
year.
from the liver, usually as a result of thrombotic
occlusion of the hepatic veins. Presentation can be
fulminant, acute, subacute or chronic. The classic
presentation of Budd–Chiari syndrome is a triad
of abdominal pain, ascites and hepatomegaly,
although it can be asymptomatic in up to 20% of
patients, usually in the presence of large collaterals
from the hepatic veins.
and an underlying myeloproliferative neoplasm
are present in approximately 50% of cases.
is therefore worth considering the diagnosis in all
87
Hypercoagulable states
Resuscitation and
balloon tamponade
patients with liver dysfunction and a background
history of either a prothrombotic tendency or
myeloproliferative disorder.
will demonstrate absent or reduced hepatic venous
outflow, with CT demonstrating abnormal liver
perfusion.
Referral to an expert centre with hepatology
specialists, radiology expertise and surgical skills
86
is advised. An experienced haematologist should
also be involved in the care of the patient. Initial
management (successful in two-thirds) focuses on
anticoagulation, initially with low-molecular-weight
87
heparin.87 Life-long anticoagulation is supported by
It
guidelines from the British Committee for Standards
in Haematology.
Injection of cyanoacrylate
86
Ultrasonography
88
144
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Portal hypertension and liver transplantation
Endovascular therapy in the form of angioplasty
with stenting may be required if anticoagulation is
unsuccessful.
89
TIPSS is now considered standard
of care for Budd–Chiari syndrome if initial
anticoagulation and angioplasty are unsuccessful
and although there are no randomised data, the
results from published case series are beneficial.
A multicentre retrospective study of 124 patients
that underwent TIPSS for Budd–Chiari syndrome
reported 12- and 60-month liver transplant-free
survival of 88% and 78%, respectively.90 In a further
multicentre study of 62 patients the 12- and
60-month liver transplant-free survival following
TIPSS was 88% and 72%, respectively.91 Recent
data from a large single-centre study of 67 patients
reported survival rates of 92%, 80% and 72% at 12,
60 and 120months, respectively.
86
86
Interestingly, hepatic encephalopathy is less of a
concern with TIPSS for Budd–Chiari syndrome
as the reduction in hepatic congestion generally
improves liver function.
86
An alternative to TIPSS
is surgical shunting, but the decision to proceed to
a surgical shunt should be made at a specialist liver
transplant centre, generally when TIPSS has failed
and in patients who have no liver dysfunction and are
not candidates for liver transplantation.
87
In a small
subgroup of patients, TIPSS is unsuccessful and liver
transplantation needs to be considered, particularly
if there is evidence of hepatic decompensation and
jaundice. The relationship between hepatocellular
carcinoma and Budd–Chiari syndrome is uncertain
but in one study that included 97 patients with
Budd–Chiari syndrome, hepatocellular carcinoma
occurred in 4% of patients after 5 years of
follow-up.92 The AASLD practice guidelines suggest
6-monthly hepatocellular carcinoma surveillance in
chronic Budd–Chiari syndrome.93 Overall, however,
prognosis is good, with 5-year survival approaching
94
90%.
Portal vein thrombosis
Portal vein thrombosis is a rare condition that
is associated with a range of precipitating
factors, including cirrhosis, cancer, surgery,
intra-abdominal infection, hypercoagulable
states, myeloproliferative conditions and
extrinsic compression of the vein. Often it is a
combination of these factors that leads to portal
vein thrombosis.
thrombosis is estimated to be 0.7 per 100 000 per
year and in the absence of underlying malignancy
and cirrhosis, survival at 1year and 5years is 92%
and 76%, respectively.
can present acutely or chronically, with the latter
more likely to result in variceal bleeding due to
portal hypertension.
95
The incidence of portal vein
96
Portal vein thrombosis
1
Treatment of portal vein thrombosis depends on the
overall clinical picture of the patient and takes into
consideration the presence of symptoms, the degree
of reversibility of the precipitating causes, malignancy
and cirrhosis. Medical management may involve
observation with no active therapy (particularly if the
patient is asymptomatic and has an obvious reversible
precipitating cause, e.g. abdominal infection or
pancreatitis) or anticoagulation (with a low threshold
in malignancy and thrombosis extending into
mesenteric veins or progressing on imaging without
treatment). Conventional anticoagulant drugs such as
low-molecular-weight heparin and warfarin may be
used in cirrhotic patients with portal vein thrombosis,
particularly in those eligible for liver transplantation
as this may mitigate propagation of the clot, thus
facilitating or even permitting transplantation.
97
The presence of portal vein thrombosis is not a
contraindication to liver transplantation, but the
procedure may not be feasible if the thrombus
extends into the entire portomesenteric system.
98
Thrombectomy or thrombolysis may be considered if
there is progressive abdominal pain suggestive of an
emergency presentation with mesenteric ischaemia.
99
Endovascular options in the setting of acute portal
vein thrombosis include mechanical recanalisation,
local targeted thrombolysis, or a combination
of these treatments.
1
Radiological interventions
have extended into the portal venous system by
percutaneous transhepatic, transjugular and even
the transplenic routes in selected cases.
100
Acute
portal vein thrombus can also be treated by TIPSS
combined with a combination of techniques for
thrombolysis (e.g. clot disruption by balloon,
suction embolectomy, basket extraction of clot and
mechanical thrombectomy) but these carry the risk
of vascular trauma.
95
Prevention of re-bleeds
In the context of variceal haemorrhage, re-bleeding
is defined as any bleed that arises >48 hours after
the initial admission (as long as the patient has been
free of bleeding for at least 24 hours). ‘Early’ rebleeding is defined as re-bleeding within 6weeks of
the initial bleed, while ‘late’ re-bleeding is defined
as re-bleeding after 6 weeks.45 When haemostasis
is initially achieved with endoscopic therapy,
re-bleeding occurs in up to 30% of patients.
Recurrent variceal haemorrhage requiring salvage
TIPSS is associated with a high mortality.
41
Bleeding gastric varices, active bleeding at the
time of endoscopy, low serum albumin, renal failure
and a HVPG >
predictive factors for early re-bleeding.
20 mmHg have been described as
102–104
factors associated with late re-bleeding include liver
decompensation, presence of ascites, underlying
hepatocellular carcinoma, active alcohol use and
high-risk stigmata on endoscopy (e.g. red wale
105
sign).
101
Risk
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145
Chapter 8
Meta-analyses of studies using beta-blocker
therapy to prevent re-bleeding have demonstrated
both a significant reduction in mortality (27% vs
20%) and a decreased incidence of re-bleeding
(63% vs 42%).
18
Beta-blockers and EBL combination therapy are
recommended as the optimal secondary prophylaxis
strategy against re-bleeding.14 It is suggested that
varices are banded at 2–4-weekly intervals until
eradication. After successful eradication of varices,
patients should be followed up by repeat endoscopy
at 3months, then 6-monthly intervals thereafter, with
any recurrent varices being treated with further EBL.
14
In the early TIPSS trial, patients randomised to
receive early TIPSS (<
72 hours after index variceal
bleed) had a 1-year probability of remaining free of
re-bleeding that was significantly lower compared
with those randomised to medical therapy with EBL
(50% vs 97 %, P
In a meta-analysis published before this early
trial, a decreased incidence of recurrent variceal
bleeding and decreased mortality due to re-bleeding
were also reported with TIPSS, but at the expense of
an increased rate of encephalopathy and no overall
reduction in mortality.
< 0.001).
41
50
TIPSS is therefore reserved for those who re-bleed
despite combined beta-blocker and EBL therapy.14
Shunt surgery can also be recommended where local
expertise and resources are available in Child–Pugh
A and B patients when TIPSS is not feasible.
14
Liver transplantation
The gold standard treatment for end-stage liver
disease is liver transplantation. In 2013, across
seven transplant units in the UK (three of which
perform paediatric liver transplantation), 871 liver
transplants were performed. In April 2014, there
were 512 patients registered on the liver transplant
waiting list. Current waiting time on the adult liver
transplant list is 142days while paediatric patients
wait on average 78days.
Living donor liver transplantation is technically
challenging and has a 38% risk of morbidity to
the donor with an estimated donor mortality rate
of 0.18%.
106
Therefore, the vast majority of liver
transplants performed (particularly in the Western
world) are from whole livers obtained from
deceased donors. An important variation is split liver
transplantation. Most commonly the graft is split
between an adult and a child and the liver is divided
into an extended right lobe graft (segments IV–
98
VIII) (for the adult recipient) and a partial left graft
that includes segments II and III (for the paediatric
recipient). Both in situ and ex situ liver splitting has
been described. Split liver for two adults has also
been described, although results are less good.
With a greater demand for transplantation, extended criteria liver grafts are increasingly utilised.
However, these grafts are much more vulnerable to
ischaemic injury due to pre-existing pathology.
107,108
There is no uniform classification of an extended
criteria liver graft, but risk factors such as increased
donor age, high serum sodium, low blood pressure,
liver steatosis and prolonged cold ischaemic times
are recognised as being harmful to graft function.
An objective donor liver index including duration
of cold ischaemia, cause of donor death, donor race
and height and type of donor correlates with outcome
following transplantation.
liver index has been described that takes into
account donor age, sex, type of donor, height,
bilirubin, smoking history and whether the liver
was split.
111
110
Recently, a UK donor
109
Donation after circulatory death (DCD) represents
nearly 50% of the donor population in the UK but
only 36% of the livers are utilised. Compared to
liver grafts from donation after brainstem death
(DBD) donors, DCD grafts suffer prolonged warm
ischaemic times and this contributes to an increased
incidence of biliary complications, ischaemic
cholangiopathy, graft loss and mortality following
transplantation.
112
Indication
Patients should be considered for liver transplantation
if they have a projected life expectancy (without
transplantation) of <
quality of life (e.g. secondary to persistent intractable
pruritis or chronic encephalopathy) and providing
that they have a 50% predicted 5-year posttransplant survival. The major indications for liver
transplantation are acute liver failure, end-stage liver
disease in patients in whom transplantation would
extend life expectancy and hepatocellular carcinoma
(usually on a background of liver dysfunction that
precludes liver resection). In practical terms, patients
should be referred for transplant assessment when
major complications of cirrhosis develop, such as
variceal haemorrhage, ascites, hepatorenal syndrome
and encephalopathy. Other ‘variant’ syndromes that
fulfil criteria for elective listing include diuretic
resistant ascites, hepatopulmonary syndrome,
familial amyloidosis, primary hyperlipidaemias and
polycystic liver disease.
1 year or an unacceptable
98
146
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Portal hypertension and liver transplantation
The Milan criteria outline when liver transplantation should be considered for hepatocellular
carcinoma (HCC) and include solitary HCC with
a diameter <
diameter <3 cm and no evidence of extrahepatic
spread or vascular invasion.
5 cm, or up to three nodules with a
113
Recently. extension
of the Milan criteria was adopted by NHS Blood
and Transplant in the UK with up to five lesions
3 cm permitted, or a solitary 5–7 cm lesion
<
downstaged with local therapy and chemotherapy,
provided there is <20% growth and no new
nodules appearing over a 6-month period. An
alpha-fetoprotein (AFP) level >10 000 ng/mL was
previously considered a contraindication as it
correlates with vascular invasion and loss of tumour
differentiation. However, more recent evidence
from Duvoux and colleagues suggests that an AFP
1000 ng/mL may correlate with recurrence
level >
of HCC.
114
This work led to the adoption of the
Duvoux criteria when considering downstaged
HCC (Table 8.3). This combines AFP level with
tumour size and number of nodules. A score of ≤2
points following downstaging treatment is now used
to determine eligibility for liver transplantation in
the UK. Other criteria for transplanting HCC are
considered elsewhere and include the San Francisco
criteria (single lesion ≤
≤4.5 cm with a total tumour diameter ≤8 cm).
6.5 cm, or 2–3 lesions of
115
Donor hepatectomy
The liver is assessed at the time of retrieval for
consistency, colour and sharpness of the edges,
which can all give an indication regarding quality
of the graft and whether there is steatosis. It is
important to accurately estimate the size of the
liver and relay this to the implanting surgeon as
the weight of the liver graft may influence recipient
selection. The graft-to-recipient weight ratio should
Table8.3 • Duvoux criteria scoring system
Variable Points
Largest diameter tumour (cm)
≤3 0
3–6 1
>6 4
Number of nodules
1–3 0
≥4 2
Alpha-fetoprotein level (ng/mL)
≤100 0
100–1000 2
>1000 3
be at least 0.8% and more formal weighing of the
graft can be performed following completion of the
donor hepatectomy.
98
After donor checks are performed and relevant
paperwork is reviewed, a midline laparotomy is
performed in the donor. The round ligament and the
falciform ligament are divided. The chest is opened,
adhesions to the liver taken down and the left
triangular ligament is divided. The hepatogastric
ligament is inspected for the presence of an aberrant
left hepatic artery. The presence of an aberrant right
hepatic artery is initially assessed by palpation for
an arterial pulsation lateral and posterior to the
portal vein.
The common bile duct is divided above the
duodenum, ligating the distal end. To minimise
biliary injury due to stagnant bile, the gallbladder
is incised and irrigated until clear fluid drains
from the cut end of the bile duct. The amount of
dissection in the liver hilum depends on the surgeon’s
experience, but in general identification and control
of the gastroduodenal artery and splenic artery are
sufficient in the warm phase. Intravenous heparin
is administered, the distal aorta is ligated and then
the infra-renal aorta is cannulated in preparation for
cold perfusion. Dual liver perfusion via the portal
vein is useful particularly in DCD.
The supracoeliac aorta is clamped, the venous
drainage is achieved by venting the suprahepatic
inferior vena cava and cold perfusion is commenced.
The entire abdominal cavity is packed with slush ice
to allow rapid in situ cooling of the liver, including
above the diaphragm in the costodiaphragmatic
angles. In the DCD setting after treatment withdrawal,
asystolic arrest and verification of death, the donor
is transferred to the operating theatre and a rapid
laparotomy is carried out, followed by immediate
perfusion with cold preservation fluid.
116
During the cold phase of the operation, the
infrahepatic inferior vena cava (IVC) is divided
above the renal veins. The cold dissection
commences in the hilum by dividing the previously
identified gastroduodenal artery. The portal vein is
divided approximately 1 cm above the duodenum.
The common hepatic artery is followed towards
the coeliac axis. The origin of the splenic artery is
then divided leaving a 5-mm stump to allow for
arterial reconstruction if required. The coeliac trunk
is then taken with a patch of aorta. The diaphragm
is divided around the suprahepatic cava, starting on
the left side of the inferior vena cava, continuing
posteriorly and completing the division by taking a
patch of the right hemidiaphragm around the right
lobe of the liver. The right lobe is separated from
the right adrenal gland and the right kidney, and
the retroperitoneal tissue at the back of the inferior
vena cava. The aorta is fully divided, and the liver
is removed.
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147
Chapter 8
Once removed, the liver is placed on ice before
being perfused on the back table at the donor
centre. The liver should be kept at 4°C throughout
the bench procedure by submerging it in slushy
iced water. The liver is checked for injuries, size
and degree of steatosis. The vena cava is dissected
and the phrenic and adrenal veins stumps are
ligated to avoid bleeding on reperfusion. The
portal vein is dissected for an adequate length. The
hepatic artery is then dissected and check made for
aberrant or missed arteries. The right hepatic artery
is reconstructed if required and all the vessels are
flushed to assess for integrity and leaks.
Recipient hepatectomy
Liver
Figure8.5 • Implantation with end-to-end anastomosis
between the supra- and infrahepatic donor cava and the
respective ends of the recipient IVC.
The recipient hepatectomy aims to safely remove the
diseased liver with preservation of the venous outflow
into the IVC, portal venous inflow and hepatic artery
inflow. The bile duct is preserved to enable a duct–
duct anastomosis. A portal–caval anastomosis is not
mandatory during the recipient hepatectomy, but
when performed it preserves mesenteric outflow and
can minimise bowel oedema and bleeding.
Implant
Three major techniques for liver implantation have
been described, which differ according to the type of
venous outflow of the graft. If the recipient IVC has
been excised with the cirrhotic liver, implantation
involves an end-to-end anastomosis between
the supra- and infrahepatic donor cava and the
respective ends of the recipient IVC (Fig.8.5).
If the recipient vena cava has been preserved
and the hepatic veins (either middle and left or
all three) have been preserved, the liver can be
implanted using a ‘piggy-back’ technique whereby
the suprahepatic IVC is anastomosed to the middle
and left of all three recipient hepatic veins (Fig.8.6).
A third option is a ‘modified piggy-back technique’,
which involves preservation of the native inferior
vena cava and a side-to-side anastomosis with the
donor’s inferior vena cava (Fig.8.7).
The advantage of the ‘piggy-back’ technique is
the preservation of the systemic venous return from
the lower body and mesenteric venous return (if
a portocaval shunt has been created). The caval
anastomosis is followed by reconstruction of the
portal vein in an end-to-end manner (after which the
liver is reperfused) and then reconstruction of the
hepatic artery. Biliary drainage is usually fashioned
with an end-to-end anastomosis between the donor
and recipient common bile duct. Alternatively, a
biliary reconstruction with Roux-en-Y hepaticojejunostomy can be performed.
Complications
The risk of graft primary non-function is approximately 1% for DBD liver transplants and 2% for DCD
liver transplants. There is a relatively low incidence of
Figure8.6 • Implantation with a ‘piggy-back’ technique whereby the suprahepatic inferior vena cava is anastomosed to
the middle and left or all three recipient hepatic veins.
148
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Portal hypertension and liver transplantation
Figure8.7 • ‘Modified piggy-back’ technique, with
preservation of the native inferior vena cava and a side-toside anastomosis with the donor’s inferior vena cava.
biliary infection and anastomotic strictures requiring
intervention or surgery.
117
A previous meta-analysis
included 25 studies with 62 184 liver transplant
recipients (DCD = 2478 and DBD = 59 706) and
reported that in comparison to DBD, there was a
significant increase in biliary complications [OR = 2.4
(1.9, 3.1); P <0.00001] and ischaemic cholangiopathy
[OR = 10.5 (5.7, 19.5); P < 0.00001] following
DCD liver transplantation. The overall incidence
of biliary complications was 26% following DCD
liver transplantation compared to 16% following
DBD liver transplantation. The overall incidence of
ischaemic cholangiopathy was 16% following DCD
liver transplantation compared to 3% following DBD
liver transplantation.
112
Acute rejection can occur
in as many as 40% of the patients during the first
3months post-transplantation. Liver biopsy may be
required to distinguish between rejection and viral
infection. Pulse steroids, antithymocyte globulin, or
other adaptions of the immunosuppressive regimen
usually manage rejection episodes. Re-transplantation
is the last option when therapy fails and the patient
re-develops hepatic failure.
Immunosuppression
Triple immunosuppression therapy with tacrolimus
in combination with either azathioprine or mycophenolate mofetil and a short period of steroids (usually
3 months) is the backbone of immunosuppression
regimens after liver transplantation. Side-effects
of long-term immunosuppression include raised
blood pressure, renal dysfunction, diabetes and an
increased risk of malignancy, such as skin cancer and
lymphoproliferative disorders.
hepatic artery thrombosis (1–7%, depending on the
graft type) but this leads to a roughly 50% chance of
Results
graft loss and if it occurs within 21days it is considered
an indication for super-urgent re-transplantation.98
Outflow obstruction caused by stenosis at the caval
anastomosis is a rare but serious complication, with
a reported incidence of 1–6%. Portal vein thrombosis
occurs with an incidence of 2–26%.
98
Biliary
complications include ischaemic cholangiopathy,
as well as bile leak, bile duct necrosis, biliary casts,
According to the European Liver Transplant Registry,
since 2000, survival at 1-, 3- and 6-months post-liver
transplantation is 94%, 91% and 88%, respectively.
When considering only patients who survive beyond
6months, patient survival rates are excellent (96%
at 1year, 83% at 5years, 71% at 10years, 61% at
15years and 52% at 20years).
106
Key points
• Patients with grade II varices or worse who have not bled should be treated with beta-blockers
unless there are medical contraindications.
• Endoscopic band ligation (EBL) is the initial treatment of choice for acute variceal bleeding.
• After bleeding, patients should enter a programme of variceal ligation or beta-blockade to prevent
recurrent bleeding.
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149
Chapter 8
• Transjugular intrahepatic portosystemic systemic shunt (TIPSS) should be considered in patients in
whom endoscopic therapy is unsuccessful.
• After satisfactory haemostasis with first-line therapy, and depending on local resources, early TIPSS
(<
72 hours after index variceal bleed) can also be considered in selected patients with Child–Pugh B
cirrhosis and active bleeding at initial endoscopy, or Child–Pugh C cirrhosis with Child–Pugh score <14.
• Liver transplantation should be considered in appropriate cases once variceal bleeding is
problematic.
• Shunt surgery should be considered for non-cirrhotic patients with recurrent variceal bleeding and for
Child–Pugh A and B patients who do not have access to TIPSS or transplantation.
• Liver transplantation offers the definitive treatment for portal hypertension secondary to cirrhosis.
• Due to the scarcity of organs the trend to use DCD donors as a source of livers continues to increase
but these livers have a higher incidence of biliary complications.
Full references available at http://expertconsult.
inkling.com
Key references
18. D'AmicoG, Pagliaro L, BoschJ. Pharmacological
treatment of portal hypertension: an evidence-based
approach. Semin Liver Dis 1999;19(4):475–505.
PMID: 10643630.
Meta-analysis demonstrating decreased bleeding risk
with beta-blockers and grade II varices.
36. Chavez-Tapia NC, Barrientos-Gutierrez T, TellezAvilaFI, etal. Antibiotic prophylaxis for cirrhotic
patients with upper gastrointestinal bleeding.
Cochrane Database Syst Rev 2010;(9):CD002907.
PMID: 20824832.
Cochrane meta-analysis showing reduced mortality,
infections and decreased re-bleeding with antibiotics
in patients with variceal bleeding.
38. Laine L, Cook D. Endoscopic ligation compared
with sclerotherapy for treatment of esophageal
variceal bleeding: a meta-analysis. Ann Intern Med
1995;123(4):280–7. PMID: 7611595.
Meta-analysis reporting lower rates of re-bleeding,
mortality and stricture formation with band ligation
versus sclerotherapy in patients with variceal bleeding.
41. Garcia-Pagan JC, Caca K, Bureau C, et al. Early
use of TIPS in patients with cirrhosis and variceal
bleeding. N Engl J Med 2010;362(25):2370–9.
PMID: 20573925.
RCT demonstrating better survival in early TIPSS in
Child–Pugh B patients and Child–Pugh C patients with
a score <14.
50. Zheng M, Chen Y, Bai J, et al. Transjugular
intrahepatic portosystemic shunt versus endo scopic
therapy in the secondary prophylaxis of variceal
rebleeding in cirrhotic patients: meta-analysis
update. J Clin Gastroenterol 2008;42(5):507–16.
PMID: 18344888.
Meta-analysis reporting decreased incidence of
recurrent variceal bleeding and decreased deaths
due to re-bleeding with TIPSS compared to medical
therapy with band ligation but increased rates of
encephalopathy and no survival benefit.
63. Khan S, Tudur Smith C, Williamson P, et al.
Portosystemic shunts versus endoscopic therapy
for variceal rebleeding in patients with cirrhosis.
Cochrane Database Syst Rev 2006;(4):CD000553.
PMID: 17054131.
Cochrane review comparing surgical shunts with TIPSS
with endoscopy for variceal bleeding reported a lower
risk of re-bleeding and occlusion with surgery but a
higher incidence of encephalopathy and no mortality
benefit.
77. MonescilloA, Martinez-LagaresF, Ruiz-del-ArbolL,
etal. Influence of portal hypertension and its early
decompression by TIPS placement on the outcome
of variceal bleeding. Hepatology 2004;40(4):
793–801. PMID: 15382120.
RCT demonstrating better survival in early TIPSS in
patients with HVPG >
20 mmHg.
150
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9
Pancreas and islet transplantation
Andrew Sutherland
John Casey
Introduction
The discovery of insulin by Banting and Best in the
early part of the 20th century saw type I diabetes
become a treatable chronic illness rather than a
rapidly fatal diagnosis. Since then, patients with
diabetes have been able to lead relatively normal
lives thanks to ongoing refinements in insulin
therapy. Despite this, many patients will suffer from
the secondary complications of diabetes, including
retinopathy, neuropathy, nephropathy and
premature cardiovascular disease. The prognosis
for a patient who has diabetic nephropathy is
poor and the 10-year survival for a 45-year-old on
dialysis is <10%.
simultaneous pancreas and kidney transplantation
(SPK). This not only removes the need for dialysis,
but also results in normoglycaemia without the
need for insulin in >85% of patients.
transplant alone (PTA) is reserved for patients in
the absence of renal disease with life-threatening
complications of diabetes, principally intractable
impaired awareness of hypoglycaemia (IAH). For
this set of patients, the risk of the surgery and
life-long immunosuppression outweighs the risk
associated with IAH and coma.
Unfortunately the morbidity and mortality
associated with pancreas transplantation means
that only a limited number of patients are
deemed fit enough for surgery. An alternative
treatment for these patients is islet transplantation.
Many of the complications of whole pancreas
transplantation are associated with the exocrine
portion of the pancreas (pancreatitis, pancreatic
1
These patients can benefit from
2
Pancreas
fistula). The islets of Langerhans account for only
1% of pancreatic mass but contain the beta and
alpha cells responsible for insulin and glucagon
production necessary for glycaemic control. Islet
cell isolation and transplantation has emerged
over the last decade as an excellent treatment
option for intractable hypoglycaemic awareness
and offers a much lower risk alternative to PTA.
Together pancreas transplant and islet transplant
come under the banner of ‘beta-cell replacement
therapy’.
Pancreas transplantation
History of pancreas
transplantation
The first pancreas transplant was performed over
50years ago in the University of Minnesota in 1966.
Early experience with pancreatic transplantation
was disappointing and remained so for many years.
Difficulties were related to the management of the
exocrine secretions and septic complications, a
high incidence of thrombosis, acute rejection and
pancreatitis. For the first half of its 50-year history,
less than 1200 pancreas transplants were performed
worldwide. Even after the introduction of ciclosporin
in 1983, 1-year patient and graft survival rates were
only 75% and 37%, respectively. Understandably,
in the 1970s and 1980s enthusiasm for pancreas
transplantation was scarce; the predominant
sentiment was scepticism. Throughout the 1990s
3
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151