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| John Karani is a consultant
radiologist at Kings College
Hospital, London. He is a member
of the Hepatology, Hepatobiliary
and Pancreatic Working Group, is a
Regional Education Adviser for the
Royal College of Radiologists and a
Member of the Higher Surgical
Training Committee at London
Deanery. Dr Karani has a special
interest in adult and paediatric
liver disease, and has authored
over 100 original articles in
peer-reviewed journals.
He regularly lectures at national
and international meetings and is
Chief European Editor at
e-Medicine Radiology and a
reviewer for eight National and
European journals. |
The role of imaging in liver transplantation
John Karani and Dominic Yu
Department of Radiology, King’s College Hospital,
London, UK
Address for correspondence:
Dr J Karani
Consultant Radiologist
King’s College Hospital
Denmark Hill
London SE5 9RS
UK
Tel: +44 (0)207 346 4599
Fax: +44 (0)207 346 3157
Email: john.karani@kingsch.nhs.uk
Abstract
Liver transplantation is the accepted treatment for
patients with irreversible hepatocellular failure and in
selected patients with hepatocellular carcinoma.
Survival rate has continued to improve as a result of
careful patient selection, as well as improvements in
graft preservation, surgical techniques and
immunosuppression. Radiology is an essential part of
a successful transplant programme; assessment of the
transplant candidate, recognition of post-transplant
complications, interventional treatment and follow-up
of transplant recipients require accurate diagnostic
imaging and interventional radiological input.
Introduction
The first human liver transplant that resulted in
prolonged survival was carried out by Starzl in 1967.1
Since then, more than 50,000 liver transplants have
been carried out worldwide.With careful patient
selection, improved graft preservation and surgical
techniques, as well as a better understanding of
rejection and immunotherapy, the survival rate by
1993 was 83% at 1 year and 74% at 4 years.2 Liver
transplantation is now the accepted treatment for
patients with irreversible hepatocellular failure and in
selected patients with hepatocellular carcinomas (HCC).
Transplantation is a dynamic field of innovative surgery
where new radiological challenges in diagnosis and
intervention continue to arise.
Progressive irreversible hepatocellular failure in
established chronic liver disease is the most common
indication for transplantation. Primary biliary cirrhosis,
chronic active hepatitis, sclerosing cholangitis and
alcoholic cirrhosis are the common causes in adults. In
children, biliary atresia and metabolic disorders are the
principal indications. Acute liver failure caused by viral
or toxin-induced hepatitis provides the greatest
challenge, as these patients are likely to have
multi-organ failure. Increasing evidence suggests that
with careful patient selection, liver transplantation is
the treatment of choice in patients with small HCCs or a small number of HCCs. In a recent study of 122
patients with single tumours <5 cm or less than three
tumours =3 cm, the 5-year survival was 80%.3
 |
| Figure 1. Contrast-enhanced CT showing a fatty native left lobe and right |
A variety of transplant techniques have been developed
depending on the indication for transplantation and the
availability of whole, reduced, segmental, auxiliary, split
or living donors. In auxiliary transplantation, part or the
entire native liver is left in the recipient, so that it can
be used in reversible acute liver failure where the graft
provides temporary function (Figure 1).
On recovery of the native liver with restoration of
function, immunosuppression can be withdrawn, with
subsequent atrophy of the graft. An auxiliary transplant
can also be used in non-cirrhotic in-born errors of
metabolism such as Crigler-Najjar syndrome. Split liver
transplantation is the splitting of a whole liver into two
grafts, the left lateral segment for a child (Figure 2) and
the residual right lobe for an adult.
 |
| Figure 2. Contrast-enhanced CT of left lateral segment graft in a child. |
Living donor transplantation began with parents
donating left lateral segments for their children, but
now right lobe grafts are also used in the adult
population. Living related liver transplantation increases
the number of organs available for transplantation and
allows surgery to be carried out on an elective basis.
Pre-transplant imaging
The role of imaging in pre-transplant assessment is
predominantly recognition of the sequelae of chronic
liver disease or developmental anomalies that may alter
the surgical approach or contra-indicate transplantation.
Fifteen per cent of patients with end-stage cirrhosis
have portal vein thrombosis,4 and although this is no
longer considered an absolute contra-indication to
transplantation, it requires surgical modification. A
venous conduit may be constructed from the junction
of the splenic and superior mesenteric veins (SMV),
which means that SMV patency must be assessed. In
end-stage cirrhosis, colour Doppler ultrasound (CDUS)
assessment of the portal vein may be difficult because
of the high reflectivity of the cirrhotic liver, fatty
change and slow flow in portal hypertension.
Ultrasound contrast agents can be used to improve the
colour and spectral Doppler signal, and if doubt
remains, indirect portography or magnetic resonance
(MR) portal venography is indicated. Biliary atresia, the
most common indication for elective paediatric transplantation,
may be associated with other developmental
anomalies including situs inversus, portal hypoplasia,
polysplenia and caval interruption; such features may
require surgical modification.
Accurate radiological staging in defining suitable
candidates with HCC for transplantation is of the
utmost importance. The rate of recurrence is
influenced by:
tumour size and number
histological type and differentiation
the presence of vascular and lymph-node involvement.
Magnetic resonance imaging (MRI) with a
hepatocyte-specific contrast agent is more sensitive
than computerised tomography (CT) in detecting small
HCC, although CT remains more sensitive in detecting
extra-hepatic disease.
In living donor transplantation, pre-operative evaluation
of the donor includes: MRI to detect focal liver lesions;
accurate determination of liver volume, which is crucial
to ensure adequate post-operative liver function for
both donor and recipient; and MR cholangiography and
digital subtracted angiography to demonstrate biliary
and vascular anatomy for surgical planning.5 In acute
liver failure, radiology plays a limited role and is mainly
used in diagnosing non-hepatic sequelae of
cardiorespiratory, renal and in particular intracerebral
complications that may present a neurological
contraindication to transplantation.
Intra-operative imaging
Intra-operative ultrasound is used to identify a plane
for resection 1 cm lateral to the middle hepatic vein
during donor right hepatectomy for living donor
transplantation.
Post-operative imaging
Post-operative imaging has two main functions: to
document regeneration of liver volume in auxiliary and
living donor transplantation, which can be performed
using CT and MR; and to assess patients with suspected
complications, for which a variety of techniques can be
used. Early recognition and treatment of complications
results in improved graft survival. In the early
post-operative period, poor graft function is usually the
result of one of four causes: primary graft non-function,
sepsis, vascular insufficiency or acute rejection.
The main contribution of radiology at this stage is
confirming the integrity of the vascular anastomoses.
Hepatic artery
Hepatic artery thrombosis is the most common
vascular complication, reported in 5% of adult and
918% of paediatric transplants.6,7 In addition, despite
an increase in portal venous flow in the immediate
post-operative period, the reciprocity of flow between
the portal vein and hepatic artery can diminish and
surgery can also disrupt collateral arterial pathways.
 |
| Figure 3. Flush aortogram demonstrating a patent infrarenal conduit with
an incidental finding of left renal artery stenosis. |
Correct interpretation of the imaging (or radiological)
findings depends on the knowledge of the surgical
technique used. When the donor hepatic arterial
anatomy conventionally arises from the coeliac axis, an
end-to-end anastomosis with the recipient hepatic
artery is used. If the arterial supply is partially or
completely from the superior mesenteric artery (SMA),
bench re-fashioning of the vasculature is required to
effect a single hepatic artery for anastomosis.
An infra-renal arterial conduit using the iliac artery of
the donor is usually constructed where segmental
grafts are implanted (Figure 3).
Colour Doppler ultrasound is >90% sensitive and
up to 100% specific for hepatic artery patency.8
Failure to demonstrate an arterial signal in the
early post-operative period is an indication for
arteriography (Figure 4).
 |
| Figure 4. Selective coeliac arteriogram showing hepatic artery thrombosis
at the site of the anastomosis. |
Early surgical re-vascularisation may rescue the graft,
obviating the need for re-transplantation. The degree of
parenchymal ischaemia can be assessed with
contrast-enhanced CT. In children, neovascularisation
can occur with collaterals forming from the SMA and
splenic artery, which may develop and protect the graft
from ischaemic complications. Delayed presentation of
hepatic artery thrombosis with biliary strictures, leaks
and recurrent sepsis usually requires re-transplantation
despite stenting and drainage procedures.
 |
| Figure 5. Selective hepatic arteriogram demonstrating a stenosis at the
anastomosis. |
Hepatic artery stenosis is less common and typically
occurs at the surgical anastomosis. Stenosis can be inferred on CDUS if the systolic acceleration time is
>0.08 seconds and the resistive index is <50%.9
The finding is confirmed with angiography (Figure 5).
Angioplasty may be successful in reversing or arresting
the effects of ongoing graft ischaemia.1013
Mycotic aneurysms occurring at sites of vascular
anastomoses are rare, but rupture carries a high
mortality. Intrahepatic aneurysms may develop
following biopsy or as a result of mycotic emboli they
are usually asymptomatic and can be treated with coil
embolisation. However, surgical excision of the infected
component of intra-hepatic aneurysms is usually required.
Portal vein
 |
| Figure 6. Venous phase of a selective superior mesenteric angiogram
showing portal vein thrombosis. |
Portal vein thrombosis after liver transplantation is
uncommon, and occurs in <2% of recipients.14 In
addition, portal hypertension is immediately relieved
by liver transplantation.Variceal bleeding, ascites and
interstitial oedema in the post-operative period indicate
hindered portal venous flow, either by stenosis or
thrombosis (Figure 6).
Predisposing factors include:
•pre-existing thrombosis
•hypoplasia
•previous shunt surgery
•pro-thrombotic disorders.
If adequate collateralisation occurs, with development
of a cavernoma and reduction of portal pressure, the
graft survival may be unaffected. Stenosis of the portal
vein is rare and is confirmed by portal pressure studies
to determine the transanastomotic gradient; transplant
portal venoplasty or stent insertion can be carried
out15,16 long-term results indicate these to be a
curative procedures.
Inferior vena cava
Occlusion or stenosis of the inferior caval anastomosis
is rare and occurs in <1% of recipients. Supra-hepatic
caval stenosis results in hepatic venous outflow
obstruction and presents as the Budd-Chiari syndrome,
while infra-hepatic caval stenosis presents with
peripheral oedema. Inferior venocavography with
pressure studies is used to confirm the haemodynamic
significance. As caval strictures are fibrotic, they may
recur following venoplasty or stent insertion.
Biliary tract
Bile duct complications are an important cause of
post-surgical morbidity and mortality. Three types of
anastomosis exist: the duct-to-duct and Roux loop
hepatico-jejunostomy types have earlier presentations
than the now outdated stone-forming gallbladder
conduit. The method of anastomosis, cold, ischaemia
time and associated vascular insufficiency are factors
that critically influence the frequency, development
and type of complications.
Presenting features include:
•cholestasis
•cholangitis
•non-specific biochemical graft dysfunction
•biliary peritonitis from a leak.
 |
| Figure 7. Percutaneous transhepatic cholangiogram showing
non-anastomotic biliary strictures secondary to hepatic artery thrombosis. |
Sonographic findings may be misleading as biliary
dilatation within the graft is a variable feature. More
commonly, a high pressure/low volume biliary system
develops proximal to the stricture. Magnetic resonance
cholangiography is the investigation of choice, reserving
the more invasive endoscopic and percutaneous
cholangiography for when intervention is required.
An anastomotic stricture can be treated with dilatation
and temporary stenting, or surgical reconstruction
depending on the individual patient and the presence
of other complications. The development of nonanastomotic
strictures carries a worse complication as
these represent a diffuse biliary injury with hepatic
artery thrombosis (Figure 7), with prolonged ischaemia
and ABO incompatibility as antecedent factors.
Intraductal stones are a further complication with
secondary septic cholangitis further damaging the
biliary epithelium. Bile leaks from an anastomotic leak
or resection margin of a reduced graft present with
biliary peritonitis. Aspiration can be carried out under
ultrasound or CT guidance. Direct cholangiography
should be performed to demonstrate the site of the
leak, and should be followed by stenting.
Rejection
Acute rejection is cell mediated and characterised by
lymphocytic infiltration. It is common in the early
post-operative period and is usually successfully treated
by manipulation of immunosuppression. Radiological
findings are non-specific, and may include increased
hepatic artery resistance on CDUS and periportal
parenchymal changes on CT the diagnosis is made
on histological grounds. Chronic rejection is a process
that is characterised histologically by arteriolar
occlusive lesions and obliteration of bile ducts. It does
not respond to alterations in immunosuppression and
re-transplantation is the long-term treatment.
Malignancy
Organ transplant recipients are at increased risk for the
development of malignancy, at least in part caused by
immunosuppression therapy. Four-to-five per cent of
liver transplant recipients develop malignant tumours,
and half of these develop post-transplant
lymphoproliferative disorder (PTLD).17 Liver transplant
recipients have a four-fold increase in the incidence of
lymphoma compared with the general population;18 the
majority of which are non-Hodgkins lymphoma (NHL),
mostly of the B-cell type related to Epstein-Barr virus
infection. Post-transplant lymphoproliferative disorder
can be polyclonal or monoclonal; the former responds
to a reduction in immunosuppression while the latter
requires chemotherapy. Most commonly, PTLD involves
the lymph nodes, followed by the small bowel, the
transplant graft, pulmonary nodules and the
periventricular white matter. Skin malignancies (basal
and squamous cell) are the most common sporadic
malignancies.19 Recipients with a history of
long-standing inflammatory bowel disease and primary
sclerosing cholangitis, appear to be at a higher risk of
developing colorectal neoplasm.20
Infection
The risk of infection by viral, fungal and bacterial
agents is increased in transplant recipients as a result
of immunosuppression. Improved antibiotics have
decreased morbidity and mortality caused by bacterial
infections, but the risk of opportunistic infections has
increased. Cytomegalovirus (CMV) has become a major
source of complications as the virus itself can induce
immunosuppression, producing a flu-like illness at one
end of the spectrum to myocarditis, pancreatitis and
intestinal ulceration with fatal results at the other
extreme. Transplant recipients who lack antibodies to
CMV, receiving a graft from a CMV-positive donor, are
at particular risk. Recurrent hepatitis B and C infections
are also major sources of morbidity and mortality.
Conclusions
Improved surgical and medical techniques have
decreased the percentage of post-transplant
complications. However, with an ever-increasing
number of transplants carried out every year, the
follow-up population is steadily growing. The radiologist
needs to be aware of new surgical techniques, which
present challenges for the imaging of and interventions
for patients undergoing liver transplantation.
References
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