For the full versions of these articles see bmj.
com
1
Liver Centre, Toronto Western
Hospital/University of Toronto,
Toronto, ON, Canada M5T 2S8
2
Hepatology and Liver Transplant
Service, Addenbrooke’s Hospital,
Cambridge, UK
Correspondence to: G M Hirschfield
gideon.hirschfield@uhn.on.ca
Cite this as: BMJ 2009;338:b1670
doi:10.1136/bmj.b1670
BMJ | 30 MAY 2009 | VOLUME 338
CLINICAL REVIEW
Adult liver transplantation: what
non-specialists need to know
G M Hirschfield,1 P Gibbs,2 W J H Griffiths2
The UK has approximately 6 000 surviving liver trans-
plant recipients,1 and annually about 600 people with
liver disease receive new livers. The post-transplant
population is growing, since nearly 550 of those 600
patients are alive one year after the operation, and at
least 300 are alive 20 years after.2 3 We review liver
transplantation for a non-specialist audience, with an
emphasis on transplants in adults.
Who needs a liver transplant?
Common triggers for referral in people with chronic,
usually cirrhotic, liver disease are progressive jaun-
dice, diuretic-resistant ascites, or hepatocellular carci-
noma (box 1). Early referral is recommended since
patients vary in their disease progression, and the
assessment must be thorough. Liver transplantation is
principally aimed at restoring health and improving
survival, but, unlike other operations with similar
potential benefit, limited resources restrict the number
of people who receive transplants.
Evidence based criteria can statistically quantify the
risk of death in patients with advanced liver disease.
The Model for End-stage Liver Disease (MELD)
score (which uses a formula based on measurements
of bilirubin, creatinine, and International normalised
ratio; www.unos.org/resources/MeldPeldCalculator.
asp) accurately predicts short-term mortality.4
UKELD, the UK risk score, also predicts which
patients are at risk of dying while on the waiting list,
but its calculation additionally includes measurements
of serum sodium (which others have demonstrated
more accurately identifies patients at a greater risk of
death5). A score of 49 or greater predicts a one year
survival of less than 91%, which is equal to the mortal-
ity risk (9%) after elective transplantation.6 Such scores
therefore provide objective minimal listing criteria as
well as ways to prioritise those awaiting transplant,
based on the predicted waiting list mortality.
Syndromes for which the mortality risk is not ade-
quately reflected by such scores but which still portend
a poor prognosis—such as diuretic resistant ascites—
can also qualify an individual for transplant. However,
there is little or no evidence that patients with other
conditions, such as portopulmonary hypertension,
fatigue, or pruritus, benefit in survival terms from
transplant.7
Transplants are also recommended for hepatocellu-
lar carcinoma that complicates cirrhosis, although can-
cer recurs in 10% of cases. Doctors are cautiously
moving from restrictive size criteria (for example,
offering transplant only to patients who pre-
operatively have either one tumour <5 cm or three
tumours <3 cm), as recognition grows that the outcome
is not always poor for those with larger tumour bur-
dens. Chemoembolisation or targeted ablation ther-
apy for patients who are already on the waiting list
may improve the outcome, but there are few data
from randomised trials to support this.8
In acute liver failure, a rapid judgment commonly
within a few days is required to identify the point at
which survival with the recipient’s own liver is unli-
kely. The so-called King’s College criteria (a collection
of clinical and laboratory parameters that predict death
in acute liver failure, and thus potential benefit from
transplantation) form the basis in the UK for “super-
urgent” listing.6
How are patients assessed for liver transplant?
Liver transplant assessment must answer three ques-
tions. Is there no alternative treatment for the liver dis-
ease? If the transplant is not curative, is the recurrence
rate acceptable? And what are the unrelated medical
conditions that will contribute to overall outcomes?
Most programmes seek a chance of survival of at
least 50% at five years after the transplant. Few absolute
contraindications for transplant remain. Transplants
can be done at any age, although the outcome is less
SOURCES AND SELECTION CRITERIA
There have been few large-scale randomised controlled
trials and Cochrane reviews on liver transplantation; data
mostly come from extensive registry descriptions,
multiple case-series, or small trials. We have combined
our knowledge with that published in recent guidelines
and in articles identified by Pubmed searches with the
term liver transplantation.
1321
CLINICAL REVIEW
favourable for those over 65 years than it is for younger
people. HIV infection is no longer a contraindication
provided that the viral count is under control.9 Schizo-
phrenia, depression, and previous alcoholism and
drug abuse are not reasons to decline transplant, but
co-morbidities that should be assessed. A six month
abstinence rule applies to alcohol related disease to
reduce recidivism as well as to allow for improvement
in liver function with the hope of avoiding transplanta-
tion. Clinically harmful drinking post transplant is less
prevalent than perceived, and only an estimated 6.5%
drink heavily. Where live donor transplantation is con-
templated, the healthy individual agreeing to a partial
hepatectomy to donate a liver graft must undergo a
detailed medical and social evaluation. 10
Transplant assessment meetings are multidisciplin-
ary, and the process should be auditable. Patients who
are refused transplantation after the first assessment are
offered a second opinion. Nurse coordinators usually
Box 1 Underlying indications that can lead to transplantation
Liver failure
Acute/subacute (approximately 10% of transplants)
Drug induced:
Direct toxicity (for example, from paracetamol or herbal remedies)
Idiosyncratic (for example, from isoniazid or nitrofurantoin)
Viral hepatitis
Acute fulminant autoimmune hepatitis
Acute Budd-Chiari syndrome not amenable to radiological treatment
Metabolic disease (such as Wilson’s disease or neonatal haemochromatosis)
Chronic (usually underlying cirrhosis)
Alcohol related liver disease
Chronic hepatitis B or C virus infection
Malignancy (such as hepatocellular carcinoma, haemangioendothelioma, or, rarely,
neuroendocrine tumour)
Non-alcoholic steatohepatitis
Autoimmune hepatitis or granulomatous liver disease, including sarcoidosis
Biliary cirrhosis, usually primary; secondary causes include cystic fibrosis
Sclerosing cholangitis, usually primary; secondary causes include IgG4-associated,
histiocytosis X
Biliary atresia or Alagille’s syndrome
Haemochromatosis, Wilson’s disease, or α-1 antitrypsin deficiency
Gaucher’s disease, glycogen storage disease, Crigler-Najjar type 1, familial intrahepatic
cholestasis
Chronic Budd-Chiari syndrome
Cryptogenic cirrhosis
Surgical gene therapy
Primary oxalosis, familial amyloidosis, or familial hypercholesterolaemia
Miscellaneous (with or without significant chronic liver disease)
Polycystic liver disease, Caroli’s disease, congenital hepatic fibrosis
Portopulmonary hypertension, hepatopulmonary syndrome, nodular regenerative
hyperplasia
Recurrent cholangitis, intractable cholestatic pruritus, intractable portal hypertensive
bleeding
1322
ONGOING CHALLENGES
Reducing transplant demand
Limiting paracetamol sales
Screening and treating hepatitis C before end stage liver
disease develops
Alcohol harm avoidance programmes to reduce the
burden of alcoholic liver disease
Improving organ utility
Split liver grafting: improving surgical techniques to
reduce complications
Living donor transplantation to provide an alternative
donor source
Organ preservation strategies to increase donor numbers
Increasing organ availability
Increasing numbers of donor coordinators who manage
the donation process with bereaved families
Professional training for coordinators
Incentive schemes for intensive care units to increase
donation
“Opt out” legislation—presumed consent to organ
donation
Optimising immunosuppression post-transplant
Monoclonal antibodies with the hope of greater specificity
in immunosuppression
Investigating role of chimerism in tolerance
Alternative liver support/regeneration
Liver support devices equivalent to renal dialysis
Stem cell/hepatocyte transplantation to reverse liver
failure
Gene therapy to treat chronic liver disease
organise the assessment, which comprises a series of
investigations and consultations, with particular focus
on cardio-respiratory function. Since the average reci-
pient is over 50 years old, cardio-respiratory concerns
are common, and problems identified may lead to
medical or surgical intervention before the patient is
put on the transplant list. Smoking cessation is advo-
cated for all. Nutritional evaluation for underweight or
overweight people is important, since extremes of
body mass index can be associated with poor peri-
operative outcomes. However, direct analysis of the
data does not support exclusion based solely on
weight.11 Whether or not ethnicity contributes to
long term outcome is uncertain, but more important
is ensuring that cultural barriers (e.g. language,
perceptions of health) do not impede access to
transplantation.
How long do patients wait for a transplant?
In the UK, approximately 14% of all listed patients die
or are considered too sick before a graft is available.12
Waiting times vary by country and reflect not only
donor numbers, but also clinical caseloads, recipient
weight and blood group as well as the organ listing or
BMJ | 30 MAY 2009 | VOLUME 338

Systemic immunosuppression Psychological adjustment
a) Infection (local and systemic) Reactive depression
b) Direct side effects especially renal, Family strain
neurological, cardiovascular, bone
c) Long term malignancy risk
e.g. lymphoma, skin cancer Hepatic veins to vena cava
• Caval strictures can present with venous outflow
abnormalities e.g. lower limb oedema
Liver parenchyma
EARLY
a) Primary non-function
b) Acute rejection
c) Ischaemia-reperfusion injury
d) Impaired graft function secondary to anastomotic (biliary, vascular) complications
e) Cut surface bile leaks in split livers
LATE
a) Disease recurrence e.g. Hepatitis C, sclerosing cholangitis, alcohol, hepatocellular carcinoma
b) Chronic rejection
Portal vein
• Portal vein thrombosis/stenosis may lead
to varices and pre-sinusoidal portal hypertension
Hepatic artery
• Early hepatic artery loss (thrombosis) often leads to rapid liver failure
• Later hepatic artery loss (thrombosis/stenosis) usually presents with
ischaemic biliary strictures
Bile duct
• Anastomotic strictures present with obstruction to biliary flow
• Leaks may present as sepsis; the proximity of the anastomosis to the artery means a leak may
precipitate artery thrombosis
• Where the anastomosis is to bowel (Roux-En-Y) ascending cholangitis may also be seen
Schematic of potential complications of liver transplantation.
allocation strategies. The sickest patients benefit most
from transplantation, even with a marginal graft, and
prioritising patients according to a disease severity
score has reduced waiting times in the United
States.13 14 Adults in the UK on average wait 95 days
(www.uktransplant.org.uk/ukt/newsroom/fact_sheets).
Clinical management of patients on the waiting list aims
to minimise new complications, such as diuretic-
precipitated renal failure, and necessitates the prompt
treatment of infection. Surveillance for varices and
hepatocellular carcinoma should continue while people
are on the waiting list.
What does the operation entail?
Great progress in both liver surgery and liver trans-
plantation has occurred as a result of improved pre-
operative diagnosis, and intraoperative and
postoperative care.15 Hepatectomy, which is difficult
with severe portal hypertension or when patients
have had previous surgery, is followed by the anhepa-
tic phase and liver implantation. Three important vas-
cular anastomoses (inferior vena cava, portal vein,
hepatic artery) are created to allow reperfusion. The
biliary anastomosis can be done as duct-to-duct or as
duct-to-small bowel.
The regenerative capacity of the liver means a whole
organ may not need to be implanted. The donor organ
can be divided to use as auxiliary grafts (in which the
recipient’s liver is left in place), which may have utility
BMJ | 30 MAY 2009 | VOLUME 338
CLINICAL REVIEW
in acute liver failure. The most frequent approach gen-
erates a left lateral and a right extended liver graft for
donation to one child and one adult, respectively. In a
potential extension of this approach, the liver can be
split to provide two “full” hemi-grafts: the left side for a
small adult or a large child and the right for a medium
sized adult patient.
To maximise donor organ use, surgeons also accept
livers with potentially more marginal outcomes such as
with mild or moderate steatosis, from donors with pre-
vious hepatitis B exposure, and from those over the age
of 65. The use of non-heart beating donors is increas-
ing, although ischaemic biliary damage is a concern.
Matching the graft size between donor and recipient
is important, and matching for blood group is routine,
except in acute liver failure, in which compatibility of
blood groups is sufficient.
For living donors, the operation to remove a portion
of their liver carries a significant mortality risk of
0.8%.16 Advantages for the recipient of having a living
donor are elective surgery, a shorter waiting time and
therefore a lower MELD at transplant, excellent donor
liver function, and minimal cold/warm ischaemia.
However, vascular and biliary complications are
increased, along with a potential for “small-for-size
syndrome”.
What are the potential complications of
transplantation?
Although symptoms and post-operative examination
can identify concerns, the complexities of the surgery
and the consequences of immunosuppression mean
there is a heavy reliance on blood tests, imaging, and
liver biopsy to identify complications (figure). The
A PATIENT’S PERSPECTIVE
In retrospect, I realise that low level confusion had already
set in probably before I was admitted to hospital. I was
“liver ignorant,” had heard the liver could regenerate and
was due on holiday in 2 weeks—plenty of time to get rid of
the jaundice! Little did I appreciate that my liver was
failing and I would need a transplant for a condition I had
never heard of (“seronegative acute liver failure”). I didn’t
understand the magnitude of it, but I wasn’t frightened. I
just felt profoundly sad at the potential consequences for
my family.
After the transplant in the intensive care unit, I was
spoken to frequently, and my emotions were up and
down. The nurses were a lifeline. I did go through a phase
of thinking I might not be one of the lucky ones to get
better, but I went back to a normal life. Having people take
the time to listen to me, explain things patiently, and talk
to my family meant a lot. A liver transplant is not an
experience you would choose for yourself or your family,
but there are worse things. Aside from returning my
health, it has restored my faith in human nature. It is a
cliche but I will never be able to thank my donor (or their
family) enough as well as all those involved, not just
doctors, and not just those at the transplant centre.
Lorna Bailey
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CLINICAL REVIEW

immediate postoperative period is often uneventful,

but problems can include bleeding or poor graft func-
tion. Early postoperative patients can develop sepsis,
difficulties with vascular and biliary anastomoses, and
acute graft rejection. In the late postoperative period,
the consequences of immune suppression (such as
renal impairment, cardiovascular risk, and malig-
nancy) and disease recurrence are more frequent than
chronic graft rejection.
Common sites of infection are the chest, urine,
blood, abdomen, and indwelling cannulae. Short
term prophylaxis is given according to local guidelines
and can include valgancyclovir for cytomegalovirus,
fluconazole for fungal sepsis, septrin for pneumocystis,
and perioperative broad spectrum antibiotics.17 18
Some patients may need prophylaxis against a reacti-
vation of tuberculosis. The transmission of unusual
infections, such as rabies or arenaviruses, through
liver donation, however, is very rare. 19
Acute cellular rejection is common (roughly esti-
mated at 25-30%), and, since patients are reviewed reg-
ularly in the early post-transplant period, it is usually
identified when asymptomatic, as a result of abnormal
blood tests (such as, raised liver enzymes, bilirubin, or
eosinophil count). Non-specific symptoms such as
lethargy, fever, and abdominal pain may be presenting
features, but there are no specific symptoms or signs.
The target tissues include bile ducts and hepatic vascu-
lar endothelial cells, and liver biopsy is usually used to
grade severity and exclude alternative pathologies
(such as sepsis, recurrent disease, ischaemia, or drug
Box 2 Important interactions for those on tacrolimus,
ciclosporin, or rapamycin
Inhibitors of the cytochrome P-450 system that can
increase blood levels of immunosuppressants:
Erythromycin, clarithromycin
Clotrimazole, fluconazole, and ketoconazole
Grapefruit juice
Diltiazem, verapamil, and nicardipine
Metoclopramide
Ranitidine
Inducers of the cytochrome P-450 system that can
decrease blood levels of immunosuppressants:
Warfarin
Carbamazepine, phenytoin, and phenobarbital
Rifampin and rifabutin
toxicity). Moderate or severe rejection is treated with
methylprednisolone, usually without incident.
Chronic rejection, which usually occurs only after the
first year, is different; it is sometimes referred to as
“vanishing bile duct syndrome” because of the pro-
gressive loss of the bile ducts. Histological tests often
show a vasculopathy of the main branches of the hepa-
tic artery. Risk factors include those with previous
acute rejection, and a recent change in immunosup-
pression, including non-compliance. Patients can be
identified through routine blood tests showing
deranged liver enzymes (hepatitic or cholestatic

Common immunosuppressive agents and their side effects

Drug Mechanism Side effects Other effects
Corticosteroids, e.g. prednisolone Synthetic corticosteroid with broad Weight gain Hyperglycaemia Promotes replication of hepatitis B
20 mg daily, tapering dose anti-inflammatory effects Osteoporosis and C viruses
Azathioprine Purine synthesis inhibitor, inhibits Marrow suppression Harmful interaction with allopurinol
(1 mg/kg) cell proliferation Pancreatitis
Veno-occlusive disease
Mycophenolate mofetil (up to 1g Mycophenolic acid inhibits de novo Diarrhoea
twice a day) purine synthesis by inhibiting Marrow suppression
inosine monophosphate Headache
dehydrogenase
Tacrolimus Calcineurin inhibitor: macrolide Nephrotoxicity Reduces rate of chronic rejection in
(target trough level 5-15 μg/l, antibiotic, inhibits T-lymphocyte Neurotoxicity (seizures or comparison to ciclosporin and is
depending on time since transplant) signal transduction and interleukin- neuropathy) more reliably absorbed; NSAIDs may
2 transcription Hypertension potentiate nephrotoxicity
Diabetes
Ciclosporin Calcineurin inhibitor: inhibition of T- Nephrotoxicity May have activity against hepatitis C
(target trough level 100-200 μg/l, lymphocyte signal transduction and Neurotoxicity (seizures or virus, and might reduce PBC
depending on time since transplant) IL-2 transcription neuropathy) recurrence rates; NSAIDs may
Hypertension potentiate nephrotoxicity
Gum hypertrophy
Rapamycin Inhibition of interleukin-2 receptor Pneumonitis Has anti-tumour and anti-fibrotic
(target trough level 4-8 μg/l) signalling (mTOR inhibitor) Atypical infection effects; stop treatment before
Impaired wound healing elective surgery
Anti-lymphocyte and anti-thymocyte Lymphocyte depletion Infection Has a role in treatment of steroid-
globulin Serum sickness resistant acute rejection
Lymphoma
Anti-CD25 monoclonal antibodies Interleukin-2 receptor blockade Hypersensitivity reactions May allow delayed calcineurin
inhibitor use in those with renal
impairment
NSAIDs=non-steroidal anti-inflammatory drugs, PBC=primary biliary cirrhosis

1324 BMJ | 30 MAY 2009 | VOLUME 338


THE ROLE OF THE TRANSPLANT NURSE COORDINATOR
We have a varied but interesting role, from the first meeting
with a potential recipient, continuing through the process of
assessment, waiting, surgery and post-operative recovery. We
often become well known to our patients, and the patients
may confide in us things they don’t feel able to tell others. It is
our responsibility to ensure that the patient and their family
are fully informed about transplantation, including the ups
and the downs, and the realities and risks.
Working alongside the whole team of doctors, nurses,
pharmacists, and social workers, we ensure the patient
undergoes the various tests and procedures needed to
determine their suitability for transplantation. Being on the
waiting list is a stressful and difficult period, and we help look
after the physical and emotional needs of patients during this
time. Our on-call role is largely enjoyable, as “setting up” a
transplant for a patient who has been waiting anxiously on the
list for some time is something special. This involves liaising
closely with other members of the transplant team, including
surgeons, anaesthetists, nurses and scientists. Sometimes
it’s a “false start” and the patients all know that we won’t begin
a transplant until the team is happy the organ is a good
donation. It is extremely rewarding to see patients go on to
have successful liver transplants, but also very sad and
distressing when occasionally patients die while waiting for a
liver or after a difficult transplant.
Seeing a patient return to health and being given a new
chance of life is the best part of our role. It is crucial that we
continue to support and educate the patient and their families
through the post-operative course in order for them to leave
hospital with confidence and looking forward to their future. It
is important that they have trust in us as we are often the first
member of the hospital team they contact if they have any
questions or concerns about their health. We liaise closely
with GPs and other health and social care professionals and
like to know what’s happening to our patients, be it medical or
social. Our relationship with our patients extends to seeing
them in clinic not only at the transplant centre but increasingly
in outreach clinics.
Elizabeth Mowlem, Cambridge
patterns), if they have non-specific symptoms, or pre-
sent jaundiced with pruritus. Liver biopsy is manda-
tory for diagnosis, and immunosuppression is
increased with the hope of restoring graft function,
though not always successfully.
Immunosuppression requires several drugs (table).20
The goal is to use the lowest dose possible to maintain a
healthy graft. Most doctors start with a combination of
a calcineurin inhibitor, steroids such as prednisolone,
and azathioprine. The role of specific monoclonal anti-
bodies such as against the interleukin 2 receptor is yet
to be established.21 Patients are then weaned off predni-
solone (often by six weeks, though in some cases, such
as in those with hepatitis C, it may be avoided entirely).
Immunosuppression is subsequently either monother-
apy, in the form of tacrolimus or ciclosporin, or dual
therapy with additional azathioprine or mycopheno-
late. The largest study to date, a randomised controlled
trial in the UK, compared the effectiveness of
BMJ | 30 MAY 2009 | VOLUME 338
CLINICAL REVIEW
tacrolimus with that of ciclosporin, concluding that
tacrolimus was associated with a better clinical out-
come at one year.22 This finding was backed up by a
subsequent Cochrane review that concluded that,
compared with ciclosporin, tacrolimus was more effec-
tive at avoiding rejection and improving survival of the
graft and the individual, although patients on tacroli-
mus were more likely to develop diabetes.23
TIPS FOR GENERAL PRACTITIONERS
General concerns
Routine monitoring should include measurement of full
blood count, renal function, liver biochemistry; frequency
should be guided by time since transplant and clinical
course
To monitor immunosuppression, levels of drugs such as
tacrolimus, ciclosporin, and rapamycin are normally
taken in the mornings before the drug dose; target values
are generally managed by the transplant unit and drug
doses usually lowered over time
For metabolic risk surveillance, monitor fasting lipids,
glucose, uric acid, blood pressure; drugs usually needed
include pravastatin, calcium channel blockers, and ACE
inhibitors, though general health advice should
emphasise need for exercise, smoking cessation, and low
fat diet
Undertake surveillance for colon, cervix, breast, or skin
cancer depending on sex and age
Vaccinate for influenza and pneumococcus, but avoid live
vaccines and update patients on vaccinations for travel
Psychosocial support can be offered through support for
alcohol or drug abuse; after transplant, some patients
may need counselling or drug treatment (such as
mirtazepine or citalopram) for depression or for help with
adjusting to post-transplant life
Acute problems
Always consider the possibility of sepsis. Look at obvious
sites first (such as chest, wound, urine). Look for viral
rashes; consider abdominal source (for example
cholangitis) and atypical sites such as mouth, sinuses,
bones, heart, central nervous system.
Immunosuppression might mask common symptoms
such as fever, so normal white cell count does not exclude
infection. Consider whether patient is at acute risk of
adrenal suppression. Consider whether anything
suggests a new malignancy, including lymphoma.
Renal impairment is common: avoid dehydration and
potential drug toxicities (for example with calcineurin
inhibitors, non-steroidals, or gentamicin)
Be quick to admit patients to, or ask for help from, their
transplant unit
Rejection is rarely an out of hours concern and changes in
liver biochemistry can be discussed with the transplant
team: interpretation should be done in the context of
baseline values and the underlying disease
Consider drug interactions carefully when prescribing
drugs such as allopurinol, azathioprine, erythromycin, or
tacrolimus.
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CLINICAL REVIEW
What is the long-term outlook after transplant?
The quality of life after transplantation is good: for
example, a recent long-term study found that patients
who had survived for 10 or more years after transplan-
tation had an average quality of life score of 24.5 (Fer-
rans and Powers questionnaire, mean Quality of Life
Index score range 0 to 30), although some reported a
reduced physical functioning after transplant.24
The five year mortality is lowest in patients given
transplants for primary biliary cirrhosis and highest
in those with cancer. Second highest is in those given
transplants for acute liver failure and hepatitis C
cirrhosis.2 Although effective prophylaxis means that
hepatitis B recurrence is rare, hepatitis C will recur if
the patient is viraemic when they undergo the
transplant.25 Many doctors will treat recurrent hepatitis
C, accepting the risk of interferon precipitated rejec-
tion, because a sustained virological response offers a
survival benefit. Other diseases that can recur include
autoimmune hepatitis, primary biliary cirrhosis, and
primary sclerosing cholangitis (which can affect survi-
val). Increasingly, both in people who have had trans-
plants and those who have not, steatohepatitis is
becoming common.
By five years post-transplant, 10-20% of patients
may develop chronic renal failure, usually related to
calcineurin inhibitor toxicity.26 Hypertension occurs
in 60% of post-transplant patients (with half of these
needing more than one drug for control) and diabetes
in 35%.27 In one study, the incidence of developing
ADDITIONAL EDUCATIONAL RESOURCES
Resources for healthcare professionals
UK transplant website (www.uktransplant.org.uk/ukt)—Now known as the UK Directorate
of Organ Donation & Transplantation, within NHS Blood and Transplant
United Network for Organ Sharing (www.unos.org)—An American organisation that
oversees organ donations across the United States
American Association for the Study of Liver Diseases (www.aasld.org)—One of the leading
professional organisations with the aim of preventing and curing liver disease
The National Liver Transplant standards (www.ncg.nhs.uk/documents/ns_national_
liver_transplant_standards-010805.pdf)—A comprehensive summary of standards for
liver transplantation in the NHS
The British Transplantation Society (www.bts.org.uk)—An important professional body
advancing the study of the biological, clinical, and social problems of tissue and organ
transplantation
European Liver Transplant Registry (www.eltr.org)—A network of European liver transplant
centres that aims to register all transplants in Europe
Resources for patients
British Liver Trust (www.britishlivertrust.org.uk)—A charity providing information and
support for people with liver disease
American Liver Foundation (www.liverfoundation.org)—A charity that advocates and
promotes education, support, and research for the prevention, treatment, and cure of liver
disease
Liver transplant support (www.livertransplantsupport.co.uk)—A patient support website
Addenbrooke’s Liver Transplant Association (www.alta.org.uk)—A long standing patient
run liver transplant association.
*All these websites are free and do not need registration
1326
SUMMARY POINTS
Potential transplant recipients often outnumber donors
Improved donor schemes, broader donor criteria, split liver
grafts, and live donors (who donate a portion of their liver)
can increase the number of transplants
Long term survival after transplant is excellent
Family doctors are important in the management and
monitoring of hypertension, diabetes, hyperlipidaemia, and
renal function, and in cancer surveillance after the
transplant
The prevention of end stage liver disease and the early
detection of liver complications could reduce the number of
transplants needed
diabetes after a transplant was one in five, which is
twice that in non-transplant patients with hepatitis
C.28 Obesity is nearly as frequent as hypertension; in
one analysis, 21.6% of non-obese transplant recipients
became obese over the 2 years after transplantation.29
Such metabolic disturbances broadly relate to the
aetiology of the original disease, the side effects of
immunosuppression, and post-transplant weight gain.
What general practitioners need to do
The family doctor remains an important member of
the team caring for transplant recipients, although
their role is usually limited in the first year after surgery
because the patient will need to visit the transplant
team frequently. Later, when the family doctor
assumes greater responsibility for hypertension, dia-
betes, hyperlipidemia, and cancer surveillance, advice
is available from the transplant clinic.
Drug interactions are always important to consider
(box 2). Management by the general practitioner
should include lifestyle advice, aggressive treatment
of hypertension (with calcium channel blockers, angio-
tensin pathway inhibition, α-receptor blockade), and
screening for diabetes and hyperlipidaemia. Pravasta-
tin, unlike other statins, does not interact with calci-
neurin inhibitors and is therefore the preferred
treatment for hyperlipidaemia. Late mortality (>
5-10 years post-transplant) after liver transplantation
is often a result of malignancy.30 Transplant brings a
substantial increased incidence of almost all carcino-
mas, some of which are caused by pre-transplant risk
factors—in particular alcohol—and others by long
term immunosuppression. Common malignancies
include skin, gastrointestinal, and lymphoproliferative
disorders, so general practitioners should be proactive
in advising against sun exposure and encouraging
screening for breast, cervical, and colon cancer. The
management of acutely unwell recipients is a common
concern for non-specialists, but transplant clinics wel-
come discussion about sick patients at any time.
Contributors: GMH and WJHG contributed equally to the preparation of
this article, and both act as guarantors.
Competing interests: None declared.
Provenance and peer review: Commissioned; externally peer reviewed.
BMJ | 30 MAY 2009 | VOLUME 338

1 Transplant UK. UK transplant activity report, 2007-08. www.
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From our archive
Treating hypertension with propranolol (1964)
Fifteen out of 16 hypertensive patients given propranolol
for up to seven months have shown reductions of
blood-pressure. Propranolol alone may prove to be useful
in the treatment of mild and moderately severe cases of
hypertension. In one patient experiencing marked
drowsiness on methyldopa a change to propranolol
resulted in improved blood-pressure control
with no side-effects. Propranolol produced a
considerable hypotensive effect in patients on
adrenergic neurone-blocking and milder hypotensive
drugs.
Propranolol has so far proved relatively free from
side-effects and patients usually feel well on the drug.
We have seen one case where heart failure was
precipitated by propranolol; this has been reported
following pronethalol (Stock and Dale, 1963). We
consider that propranolol should be used with great
caution, if at all, in patients with a history suggestive of
heart failure, though one such patient with severe angina
BMJ | 30 MAY 2009 | VOLUME 338
CLINICAL REVIEW
16 Ghobrial RM, Freise CE, Trotter JF, Tong L, Ojo AO, Fair JH, et al. Donor
morbidity after living donation for liver transplantation.
Gastroenterology 2008;135:468-76.
17 Hodson EM, Craig JC, Strippoli GF, Webster AC. Antiviral medications
for preventing cytomegalovirus disease in solid organ transplant
recipients. Cochrane Database Syst Rev 2008;2:CD003774.
18 Playford EG, Webster AC, Sorrell TC, Craig JC. Systematic review and
meta-analysis of antifungal agents for preventing fungal infections in
liver transplant recipients. Eur J Clin Microbiol Infect Dis
2006;25:549-61.
19 Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL,
Ksiazek TG, et al. Transmission of rabies virus from an organ donor to
four transplant recipients. N Engl J Med 2005;352:1103-11.
20 Rosen HR. Transplantation immunology: what the clinician needs to
know for immunotherapy. Gastroenterology 2008;134:1789-801.
21 Schmeding M, Sauer IM, Kiessling A, Pratschke J, Neuhaus R,
Neuhaus P, et al. Influence of basiliximab induction therapy on long
term outcome after liver transplantation, a prospectively randomised
trial. Ann Transplant 2007;12:15-21.
22 O’Grady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A.
Tacrolimus versus microemulsified ciclosporin in liver
transplantation: the TMC randomised controlled trial. Lancet
2002;360:1119-25.
23 Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL.
Cyclosporin versus tacrolimus for liver transplanted patients.
Cochrane Database Syst Rev 2006;4:CD005161.
24 Desai R, Jamieson NV, Gimson AE, Watson CJ, Gibbs P, Bradley JA,
et al. Quality of life up to 30 years following liver transplantation.
Liver Transpl 2008;14:1473-79.
25 Gane EJ. The natural history of recurrent hepatitis C and what
influences this. Liver Transpl 2008;14:S36-44.
26 Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al.
Chronic renal failure after transplantation of a nonrenal organ. N Engl
J Med 2003;349:931-40.
27 Sheiner PA, Magliocca JF, Bodian CA, Kim-Schluger L, Altaca G,
Guarrera JV, et al. Long-term medical complications in patients
surviving > or =5 years after liver transplant. Transplantation
2000;69:781-89.
28 Saliba F, Lakehal M, Pageaux GP, Roche B, Vanlemmens C, Duvoux C,
et al. Risk factors for new-onset diabetes mellitus following liver
transplantation and impact of hepatitis C infection: an observational
multicenter study. Liver Transpl 2007;13:136-44.
29 Everhart JE, Lombardero M, Lake JR, Wiesner RH, Zetterman RK,
Hoofnagle JH. Weight change and obesity after liver transplantation:
incidence and risk factors. Liver Transpl Surg 1998;4:285-96.
30 Fung JJ, Jain A, Kwak EJ, Kusne S, Dvorchik I, Eghtesad B. De novo
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responded well without trouble. The only other side-effect
in the dosage recommended for the treatment of
hypertension, up to 200 mg. a day in divided dosage, has
been slight tiredness in 2 of the 23 patients, readily
relieved by reduction of the dosage. The side-effects seen
with larger doses used in our angina trial have also been
relieved by reducing the dose.
While a central mode of action is not excluded it is
suggested that beta-receptor-blocking drugs exert their
hypotensive action by blocking the sympathetic receptors
in the heart.
Prichard BNC, Gillam PMS. Use of propranolol
(inderal) in treatment of hypertension.
BMJ 1964;2:725-7
The entire archive of the BMJ, going back to 1840,
is now available at www.bmj.com/archive.
Cite this as: BMJ 2009;338:b1019
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