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Hakeem et al. Hepatoma Res 2023;9:38 https://dx.doi.org/10.20517/2394-5079.2023.59 Page 3 of 14

[24]
developed recurrence . Half the recurrences in this study were intra-hepatic and the authors argued if the
patients would have potentially benefited from LT rather than LR. However, these studies were
[18]
heterogeneous and included both cirrhotics and non-cirrhotics . Supportive of these data from
incidentally diagnosed iCCA, data from the Barcelona clinic on an intention-to-treat curative LR on very
early iCCA (n = 7) demonstrated a 68.6% 5-year OS with only one patient developing recurrence at 8.3
months, with a median follow-up of 23 months. Interestingly, five of these seven patients had background
liver disease, and all were minor (< 3 segments) liver resections and six of them were well to moderately
differentiated tumours .
[10]
According to a French multicentre study, cirrhotic patients with larger primary tumours may also benefit
from LT. This retrospective study from three centres compared the outcomes of patients who underwent LT
with incidental iCCA at explants (n = 49) with patients who underwent LR for iCCA (n = 26). At a median
follow-up of 25 months, the LT patients had a better 3- and 5-year OS (76% and 67%, respectively)
compared to 59% and 40% for patients who underwent LR. The LT patients enjoyed a significantly better
RFS (recurrence-free survival) at 5 years (75% vs. 36% for LR patients). The size of the largest tumour and
differentiation were identified as independent risk factors for recurrence. The study reported a similar 1-, 3-
and 5-year OS for tumours ≤ 2 cm compared with tumours > 2-5 cm which had LT - 92%, 87%
and 69% vs. 87%, 65% and 65%, respectively. These findings raise the possibility that the tumour size cut-off
could be increased to 5 cm while remaining within the Milan criteria . The role of neoadjuvant therapy
[19]
before LT for large unresectable iCCA was assessed in few studies [20,21,26] . These studies, which employed
systemic therapy and locoregional treatment with radioembolization, reported an excellent 5-year OS and
RFS of 83% and 50%, respectively [20,21,26] . The studies indicate the potential benefit of neoadjuvant/adjuvant
therapies for iCCA in LT settings and need further investigation through larger clinical trials.

CHOLANGIOCARCINOMA FIXED TERM WORKING GROUP
The International Liver Transplant Society (ILTS) Transplant Oncology Consensus Conference in 2019
reviewed the evidence for transplantation for iCCA and recommended two clear areas where this could be
performed: (1) patients with very early disease (single tumour, ≤ 2 cm) with cirrhosis and who are not
candidates for LR; (2) patients with advanced iCCA deemed unresectable in a noncirrhotic liver, if the
disease remains stable for a period of 6 months after neoadjuvant chemotherapy [27,28] .

As a result of these advancements, the Liver Advisory Group (LAG) of NHS Blood and Transplant
(NHSBT), the regulatory body responsible for overseeing all donation and transplant-related operations in
the UK, created a Fixed Term Working Group (FTWG) in June 2021, the cholangiocarcinoma-orthotopic
liver transplantation (CCA-OLT) Implementation group. The objective of the group was to develop
guidelines, protocols and processes that would enable the implementation of perihilar cholangiocarcinoma
(pCCA) and iCCA as new indications for liver transplant in the UK. The FTWG recommendations for
pCCA-OLT are not within the remits of this manuscript (this protocol is pending final approval and is not
operational yet). Similar working group recommendations for unresectable colorectal liver metastases
(CRLM) and grade 1 and 2 well-differentiated unresectable liver metastatic neuroendocrine tumours
(NETs) have been accepted as newer indications for LT in the UK and have been active since December
2022 [29,30] .

The FTWG included cholangiocarcinoma and LT patient representatives, experts in cholangiocarcinoma
surgery, LT surgery, hepatology, oncology, hepatobiliary radiology, hepatobiliary pathology, and nuclear
medicine. The group has representation from various professional bodies including British Association of
the Study of the Liver (BASL), British Liver Transplant Group (BLTG), British Transplant Society (BTS),