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Page 6 of 14 Hakeem et al. Hepatoma Res 2023;9:38 https://dx.doi.org/10.20517/2394-5079.2023.59

remain ≤ 2 cm as the current criterion and to consider expanding to > 2-5 cm after the first year of the pilot
programme, considering the number of recruited patients with tumours ≤ 2 cm. It was acknowledged that a
small proportion of patients with iCCA ≤ 2 cm may be offered resection in patients with chronic liver
disease, good synthetic functions and no portal hypertension, and tumours in locations that would enable
minor or segmental resections.

Few studies have included patients with cHCC-CCA in iCCA, leading to significant heterogeneity [16-18,38] .
The rationale for the latter grouping is that distinguishing between iCCA and cHCC-CCA for a definite
presurgical diagnosis is challenging and may not be feasible and thus more consistent with real-life clinical
practice. It is worth noting that these mixed-type tumours typically have a prognosis between pure HCC
[39]
and pure CCA, hence may not reliably indicate the oncological outcomes with LT for iCCA .

[40]
While the role of carbohydrate antigen 19-9 (CA 19-9) in liver resection for iCCA is well documented ,
there is currently no evidence suggesting a specific threshold of CA 19-9 that is associated with poor
outcomes following LT. As a result, this criterion has not been included in the evaluation process for liver
transplant candidates.

RADIOLOGICAL EVALUATION
The diagnosis of iCCA is made by a combination of radiological appearances and tissue diagnosis.
Gadoxetic acid-enhanced MRI (Primovist® in Europe/Eovist® in the US) is recommended as the standard
cross-sectional imaging, as it is the most accurate modality for identification of satellite lesions and
intrahepatic metastases, and provides better diagnostic performance and may even give prognostic
information [41-43] . The staging would include a dual-phase computed tomography (CT) of chest, abdomen
and pelvis and a positron emission tomography (PET) CT. If a patient has once been listed for transplant
and waits more than 3 months from previous cross-sectional imaging, we recommended further re-
assessment at that time point with a contrast MRI, a dual-phase CT and a PET CT. The group felt the need
for extensive evaluation to exclude patients with nascent extrahepatic disease and adverse biology to
maximise the outcomes from service evaluation. Those with poor renal function will get a non-contrast CT
of chest, abdomen and pelvis, with contrast MRI.

FITNESS ASSESSMENT & TIMING OF TRANSPLANTATION
Fitness evaluation will be as per local practice for LT assessment. Patients with iCCA with no extrahepatic
disease and considered fit for transplantation will be discussed at the local LT MDT and the cancer MDT,
and if both MDTs confirm that the patient is suitable for LT, oncologically and physiologically, the patient
will be counselled and listed for this indication [Figure 1].

The implementation group recommended that patients are transplanted within three months of listing, as
this is a life-threatening malignancy, with a risk of progression and drop out/death on the waiting list.
Unlike the technical complexity of transplantation for pCCA after radiotherapy, there is no plan for iCCA
to receive local therapy. Hence, the working group recommended all graft types be open for the iCCA
patients, including marginal grafts such as donation after circulatory death (DCD) and machine-perfused
grafts. The living donor liver transplantation (LDLT) was considered an ideal graft, as this would reduce the
waiting time after completion of assessment and also avoid competing for precious resources with other
patients on the waiting list.