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.
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 9–18% 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. |
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).
Early surgical re-vascularisation may rescue the graft, obviating the need for re-transplantation. The degree of
 |
| Figure 4. Selective coeliac arteriogram showing hepatic artery thrombosis at the site of 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 [10–13].
 |
| Figure 5. Selective hepatic arteriogram demonstrating a stenosis at the anastomosis. |
Portal vein
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).
< |
| Figure 6. Venous phase of a selective superior mesenteric angiogram showing portal vein thrombosis. |
•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 out [15,16] – 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. |
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-Hodgkin’s 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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