Mistakes in ... Booklet 2020 - 16

ueg education

Such patients can be considered for liver
transplantation provided they received a
curative treatment, are tumour free at the time
of evaluation, and have observed an appropriate
recurrence-free interval (determined by the type
of tumour involved). Survival and risk of
recurrence under immunosuppressive therapy
should be estimated, on a case-by-case basis,
with an oncologist.2 Common practice is to
consider a patient suitable for liver transplantation
if the risk of recurrence is estimated to be less
than 10% and to require an interval time of 5 years
recurrence-free to exclude potential recurrence,
though this varies by tumour type.
Although no robust data have been
published on the optimal management of
liver transplantation candidates who have a
history of extrahepatic tumours, the Israel Penn
International Transplant Tumor Registry
(www.ipittr.uc.edu/registry) is a large free online
database of outcomes after liver transplantation
in recipients with pre-existing tumours, and it can
be helpful in planning an appropriate strategy.
Returning to the cases of Mr Smith and
Mrs Christie, liver transplantation is contraindicated
for one but not the other. Mrs Christie is not a
candidate for liver transplantation because the
time that has passed since her melanoma
was treated is too short, melanoma is an
aggressive type of cancer and the tumour was
locally advanced at diagnosis. By contrast, Mr Smith
is a candidate for liver transplantation because the
interval time is long enough, the tumour was at an
early stage and it was completely removed.

Mistake 8 Not paying enough attention
to hypertension, hyperlipidaemia and
diabetes in liver transplant recipients
Liver transplant recipients frequently have
one or more features of metabolic syndrome,
which includes hypertension (40-85%),
hyperlipidaemia (40-70%), and diabetes
mellitus (10-65%).2,62 Overall, the prevalence of
metabolic syndrome in liver transplant recipients
is approximately 50-60%.63 The features of
metabolic syndrome can pre-exist (liver
transplantation does not cure the pre-existing
conditions) or be caused and/or worsened by
liver transplantation (immobilization, use of
steroids, and long-term immunosuppressive
therapy). Owing to the high prevalence of
metabolic risk factors, the cumulative risk of
cardiovascular events is approximately 25%
at 10 years post-liver transplantation, which
is significantly elevated compared with the
age- and gender-matched general population.64
Cardiovascular complications are a leading
cause of post-liver tranplantation morbidity and
mortality, and account for a third of deaths in the
long-term follow-up.65
Gastroenterologists and hepatologists tend
to focus very carefully on the management of

Mistakes in... 2020

liver-related issues in transplant recipients
(symptoms and signs of liver diseases,
recurrence and treatment of primary liver
disease, management of immunosuppressive
therapy and its complications, HCC recurrence,
etc.), but often overlook metabolic comorbidities.
A good evaluation of liver transplant recipients
should always include analysis of their metabolic
profile. Primary care teams should perform a
meticulous cardiovascular risk assessment, and
treat each of the components of metabolic
syndrome aggressively to improve patient
outcomes. The timing of the interval follow-up
should be based on general population
guidelines, as there is no specific guidance for
transplanted patients.
European and American guidelines state that
management of metabolic complications in liver
transplant recipients should start with prevention,
as interventions to prevent weight gain and its
sequelae (i.e. diet, lifestyle and physical exercise)
are more successful than attempts to induce
weight loss afterwards.2,62 These interventions
should be implemented as soon as possible after
liver transplantation, as the biggest weight gain
occurs within the first year after transplantation.
The multidisciplinary approach to metabolic
syndrome in liver transplantat recipients targets
different elements.2,62 First is the introduction of
a Mediterranean diet (<60g/day of complex
carbohydrates and a reduction of dietary
fructose are correlated with a lower risk of insulin
resistance and obesity) and physical exercise.
Second is pharmacological therapy, including
calcium-channel blockers or ACE inhibitors to treat
hypertension, statins ± ezetimibe for
hypercholesterolaemia, fish oil and fibric acid
derivates for isolated hyperlipidaemia, and
insulin and/or other agents for diabetes. Third
are changes in immunosuppressive therapy,
including conversion of ciclosporin to tacrolimus
or vice versa, reduction of calcineurin
inhibitors with the addition of other drugs (e.g.
mycophenolate mofetil), and discontinuation
of sirolimus. Fourth is evaluation of the
potential benefit of bariatric surgery for those
recipients who are, or who become, morbidly
obese despite multiple other attempts to lose
Our team usually involves a metabolic
disease specialist in the management of liver
transplantation recipients with diabetes,
especially once insulin therapy is started. From
a study from our unit, we have seen that
mycophenolate mofetil is protective versus the
development of diabetes (Becchetti and Burra,
abstract accepted for ILC 2020). New drugs for
the treatment of diabetes have recently been
approved, and they have shown good results in
terms of safety and efficacy in the general
population. Hopefully, these drugs will also prove
helpful for the treatment of diabetes in liver
transplant recipients.

Mistake 9 Late referral of patients with
decompensated cirrhosis and a possible
indication for transplantation
The evaluation of patients with cirrhosis for liver
transplantation should be considered once the
patient has experienced a major complication
of portal hypertension, such as ascites, hepatic
encephalopathy or variceal haemorrhage, or
when hepatocellular dysfunction results in a MELD
score ≥15.2,3 The evaluation process starts once
the patient is referred, which means the patient is
evaluated by a specialist transplant hepatologist.
It is important that potential candidates are
referred early, before the underlying liver disease
reaches the stage at which listing is actually
indicated. This is because multidisciplinary
assessment to evaluate transplantability is a
multistep process that takes time. From head to
foot, the assessment includes hepatology and
surgical evaluation, laboratory testing, general
health and dental assessment, nutritional
evaluation, psychology with or without
psychiatric evaluation, and cardiac and
anaesthesia evaluation.2,3 Depending on the
patient's condition and the presence of one or more
comorbidities, second-level tests may be needed.
To ensure that all potential candidates have
the same chance of being evaluated for liver
transplantation according to the principles of
justice and equity, they need to be referred when
they are ill enough to have reduced survival
and/or a poor quality of life, but are well enough
to be assessed and listed. In practical terms, this
is at the first decompensation event, when the
MELD score is ≥10 and/or the Child-Pugh is ≥B-7.
In our experience, more than one third of patients
referred to our unit need to be transferred to the
intensive care unit because they are too sick-the
mortality rate in these patients is very high.66
In our practice, we regularly communicate
with referring centres via phone calls and emails
(we have a dedicated phone number and a
dedicated email address that both operate 24/7).
Referring physicians can ask us to be involved in
liver transplantation evaluation in different ways,
according to tha patient's condition. Non-urgent
outpatient evaluation takes place within
4 weeks. Urgent outpatient evaluation takes
place within 1-2 weeks. Urgent inpatient
evaluation takes place within a few days for
hospitalized patients who are transferred to our
service. Communication with referring centres
works both ways, and patients can be transferred
back in case of clinical improvement.

Mistake 10 Assuming that liver
transplantation in patients with subacute
liver failure is indicated only once hepatic
encephalopathy occurs
Acute liver failure (ALF) is a specific syndrome
defined by acute abnormality of liver function in


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