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Page 2 of 14 Hakeem et al. Hepatoma Res 2023;9:38 https://dx.doi.org/10.20517/2394-5079.2023.59

assessment, transplant listing pathways, data management, and overall quality assurance.

Results: The FTWG recommended LT for very early iCCA in cirrhotics, who are otherwise not suitable for LR. In
this paper, we summarise the selection criteria, patient pathways, referral framework, pre-transplant assessment
criteria, outcome measures, and dissemination strategy for implementing this new indication for LT in the UK.

Conclusion: The introduction and evaluation of this pilot programme is an important breakthrough for iCCA
patients in the UK, marking a significant stride in the field of transplant oncology. The results of this service
evaluation will describe the role of LT in iCCA and guide future programmes to optimise patient selection,
management, and outcomes.

Keywords: Intrahepatic cholangiocarcinoma, liver transplantation, working group, pilot programme, outcomes

INTRODUCTION
Intrahepatic cholangiocarcinoma (iCCA), although rare, constitutes the second most common primary liver
[1]
cancer after hepatocellular carcinoma (HCC) . In the United Kingdom (UK), the incidence rate of iCCA
has nearly doubled from 1.8 to 3.3 per 100,000 from 1997 to 2017, which is an average annual percentage
[2]
change of 3.8% and this continues to increase . Despite significant advances in early diagnosis, surgical
techniques, and chemotherapy regimens, the 5-year overall survival (OS) remains dismal between
[3,4]
15%-25% . Liver cirrhosis significantly increases the risk of iCCA, with an odds ratio of
22.92 [95% confidence interval (CI), 18.24-28.79] . A National Cancer Database (NCDB) study from the
[5]
United States (US) reported 28.9% of iCCA in patients with background cirrhotic liver (Ishak Fibrosis score
5-6) . While liver resection (LR) is still considered the gold standard for curative treatment of iCCA, the
[6]
outcomes are far from ideal. The 5-year recurrence-free survival (RFS) typically ranges between 9% and
31%, with 83% experiencing local recurrence within the first two years after surgery [7-11] . Although LT would
appear an attractive option, associated chronic liver disease, tumour location, portal hypertension, and liver
failure limit the applicability of LR even in patients with small iCCA [12,13] .

Early experience in LT for iCCA, including both cirrhotic and non-cirrhotic patients, resulted in poor 1-
and 3-year OS rates of 19.4%-38% and 4.9%-10%, respectively [14,15] . However, some encouraging results from
multicentre studies have led to a re-evaluation of iCCA as a potential indication for LT in a select patient
group [16-23] . A significant proportion of these LTs are actually incidental iCCAs on explants, either because of
an unrecognized lesion not visible on pre-transplant radiology or a lesion wrongly diagnosed as HCC [19,24,25] .
Explant data from the UK of 40 iCCAs showed a median survival of 68.5 months (25.3-109.7 months), with
[25]
a reassuring 5-year OS of 57.1% .
According to a recent study from the US, out of 13 patients with iCCA, those with well-differentiated
tumours had no recurrence, while those with moderately differentiated tumours had a
recurrence rate of 78%. This highlights the significant role of tumour biology in post-transplant
outcomes . A multicentre study in Spain revealed that patients diagnosed with “very early” iCCA (defined
[22]
by tumours that are solitary and ≤ 2 cm in size) had a 73% 5-year survival rate based on a small sample size
of eight patients . In an international multicentre study, the number and size of tumours were found to
[16]
have a positive impact on long-term outcomes. Specifically, 15 patients with very early iCCA had a 5-year
survival rate of 65%, with recurrence rates similar to those of HCC within Milan criteria . Jung et al.
[18]
compared 16 LT patients with incidental iCCA, with a propensity score matched 100 iCCA patients who
underwent LR. At a mean follow-up of 39.1 months, three patients who had very early iCCA and underwent
LT had no recurrence, while six out of 26 patients (24.2%) who had very early iCCA and underwent LR had