Mistakes in ... Booklet 2020 - 15

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Mistakes in... 2020

be considered for liver transplantation after
successful downstaging to within the Milan
criteria.11
Although the Milan criteria remain the
benchmark for allocation of liver grafts to
candidates with HCC due to the excellent
outcomes post-liver transplantation,38 a modest
expansion of these criteria is reasonable and
feasible. Many proposals for how to expand the
Milan criteria have been made but consensus has
not yet been reached.39 Optimal identification of
candidates who will have a poor oncological
outcome is an ongoing issue, because HCC has
a complex biological behaviour than cannot be
determined accurately by just the number and
size of the nodules. There is evidence that
composite criteria including surrogates of
HCC biology, such as α-fetoprotein (AFP) and
response to treatment, in combination with
tumour size and number, are superior to
conventional criteria for defining suitablility for
transplantation.11 France, for instance, has already
replaced the Mlian criteria with the 'AFP model',
which includes the number of nodules, the largest
nodule diameter and the level of AFP.40
In our clinical practice, we classify HCC
aggressiveness according to stage and response
to treatment.41 Patients who have a transplantable tumour are divided into different classes
of progression (that have a different priority in
the waiting list), according to three elements:
response to bridging therapies; achievement of
downstaging to within the Milan criteria; and time
of HCC recurrence after treatment. Any selection
criteria can be used for defining a transplantable
tumour, provided a 5-year survival post-liver
transplantation of at least 60% is ensured.2,11,38 This
model allows us to prioritize patients according to
both 'urgency' (risk of drop-out during the
waiting-list time) and 'utility' (survival post-liver
transplantation) principles.

For several reasons, the occurrence of PVT
is perhaps even more important when the
patient is a candidate for liver transplantation.
First, complete PVT extending to the superior
mesenteric vein significantly increases
both morbidity and mortality after liver
transplantation.42 Second, these patients may
have or develop HCC, and HCC further increases
the risk of PVT (1-year incidence of 25%).46 In
these cases, complete PVT reduces the chance
to perform transarterial chemoembolization
(TACE).
Timely therapy is important, as anticoagulation
is more effective when given within 6 months
of the estimated diagnosis.47 Treatment of PVT
in liver transplant candidates, however, is often
delayed-and sometimes even denied-due to
fear of bleeding complications. Anticoagulation in
patients who have cirrhosis is safe,48 and a
recent meta-analysis including 257 patients with
cirrhosis and PVT confirmed the risk of bleeding in
patients with cirrhosis and PVT is comparable for
those who are treated versus those who are not.49
The same meta-analysis showed that the risk of
variceal haemorrhage was lower in patients who
were receiving anticoagulation (which would have
potentially resolved the thrombus) versus those
who were not anticoagulated.49
In our centre, all patients on the waiting list
undergo regular screening for PVT and receive
prompt anticoagulant treatment if they develop
PVT.7 When there is no response or progression is
observed during therapy, or if there is an absolute
contraindication to anticoagulation, we consider
using a transjugular intrahepatic portosystemic
shunt (TIPS).7,50

Mistake 5 Withholding treatment for portal
vein thrombosis in patients with cirrhosis
awaiting transplantation

Cirrhosis is characterized by multiple alterations
of haemostasis.51 These alterations include
thrombocytopenia and platelet function defects,
an increased level of von Willebrand factor, a
concomitant decrease of both clotting factors
and inhibitors, and altered fibrinolysis.52-54
Historically, patients with decompensated
cirrhosis were considered to be at high risk of
bleeding from invasive procedures. This belief
was because most of these patients are
thrombocytopenic (platelet count <50 x 109/L)
with a prolonged international normalized ratio
(INR). However, recent studies have shown a lack
of correlation between haemostatic alterations
and bleeding risk.55 In parallel, the thrombin
generation assay has demonstrated that the
capacity to generate thrombin (e.g. how
coagulation 'works') in patients with cirrhosis is
similar or even increased compared with that in
healthy subjects.51 It is now generally accepted
that patients with cirrhosis are not 'naturally

Portal vein thrombosis (PVT) is the most frequent
thrombotic complication in patients with
cirrhosis who are awaiting liver transplantation,
with a prevalence of up to 23%.42
The clinical impact of PVT depends on both the
extent of the thrombosis and the severity of the
underlying cirrhosis.43 Clinical manifestations of
PVT may vary from asymptomatic disease to
life-threatening complications (e.g. variceal
bleeding and/or intestinal infarction due to the
extension of thrombosis into the mesenteric
vein). In compensated patients, PVT may not be
predictive of decompensation.44 The effect of PVT
on the course of patients with decompensated
cirrhosis is not as clear, but PVT has been
associated with higher risk of failure to control
variceal bleeding45 and increased risk of death.43

Mistake 6 Assuming that patients with
decompensated cirrhosis always need
prophylactic transfusions before invasive
procedures

anticoagulated', but rather have a 'rebalanced'
haemostatic system. This precarious balance,
however, can easily be unbalanced by
superimposed factors, such as infection.56
When assessing the risk of post-procedural
bleeding in patients with cirrhosis, the first thing
to look at is the patient's condition. Is cirrhosis
compensated or decompensated? Is there
any factor that can tip the balance towards
hypocoagulability, such as infection?
Abnormalities of INR and platelet count should
not be interpreted as single measurements, but
more as trends. A chronically prolonged INR (even
if profoundly altered, e.g. 2.7) in a patient awaiting
liver transplantation for refractory ascites does
not necessarily imply there is an increased risk of
haemoperitoneum or that it should be corrected
prior to large-volume paracentesis. On the other
hand, a patient whose INR is usually 1.2 but now
presents with an INR of 2 may have an increased
risk of bleeding, as that prolongation may be an
indicator of instability in their haemostatic balance
(i.e. presence of hyperfibrinolysis).57
It's also important to stratify procedures
according to the bleeding risk. Low-risk
procedures (e.g. paracentesis using a <5-F gauge
catheter) may be performed in patients who have
any laboratory abnormality depending on
operator skill. High-risk procedures require a
different approach and that may include the
correction of INR and/or platelet count.57,58
Thromboelastography (TEG) and rotational
thromboelastometry (ROTEM) are whole-blood
viscoelastic tests that assess clot formation and
stability.59,60 They may be useful to prevent
unnecessary transfusions before procedures in
patients who have cirrhosis and coagulopathy,61
but more studies are needed to establish specific
thresholds for when transfusions are warranted
in this population.

Mistake 7 Thinking that a past history of
extrahepatic cancer is a contraindication to
liver transplantation
Consider the following two cases. Mr Smith is a
59-year-old man with HCV cirrhosis that is
decompensated by ascites and variceal bleeding.
His Model for End-Stage Liver Disease (MELD)
score is 22. In his medical history, he reports a left
hemicolectomy for stage I colon cancer in 2008.
So far, he has shown no sign of recurrence.
Mrs. Christie is a 49-year-old woman with NASH
cirrhosis complicated by multifocal HCC within
the Milan criteria that is not suitable for resection.
She had melanoma in 2017 (locoregional
disease), for which she underwent surgical
resection plus adjuvant chemotherapy. There
has been no sign of recurrence so far. Is liver
transplantation contraindicated for neither
patient, one patient or both patients?
A past history of nonhepatic tumours should not
disqualify candidates for liver transplantation.2
3



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