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Akabane et al. Hepatoma Res 2023;9:29 https://dx.doi.org/10.20517/2394-5079.2023.45 Page 3 of 9

Due to the challenges in diagnosis, a growing number of patients undergoing liver transplantation because
of end-stage liver disease or suspected HCC have either HCC or iCCA upon pathological examination,
potentially impacting patient outcomes negatively and leading to the suboptimal utilization of scarce
[20]
organs . In light of the increasing recognition that iCCA is more prevalent than previously believed, it may
be prudent to place greater emphasis on liver biopsy for the pre-liver transplantation diagnosis of iCCA.
This is especially pertinent for nodules emerging in cirrhosis that do not exhibit typical contrast
enhancement patterns in imaging studies.

LIVER RESECTION FOR LIVER CIRRHOSIS PATIENTS WITH INTRAHEPATIC
CHOLANGIOCARCINOMA
Liver resection is considered a potentially curative treatment for iCCA in patients with preserved liver
function, and it remains the first-line therapeutic option for liver cirrhosis patients with iCCA [21,22] . The
indication for liver resection in these patients is determined by several factors, including the extent of
cirrhosis, the presence and severity of portal hypertension, the patient's overall performance status, and the
location and size of the tumor [23,24] . A comprehensive assessment of liver function, typically using the Child-
Pugh classification and the Model for End-stage Liver Disease (MELD) score, is crucial for determining the
[25]
patient's suitability for liver resection .
In patients with well-compensated cirrhosis (Child-Pugh class A) and without clinically significant portal
[26]
hypertension, liver resection can be safely performed with acceptable perioperative outcomes . However,
patients with more advanced cirrhosis (Child-Pugh class B or C) or significant portal hypertension are at a
higher risk of postoperative complications, including liver failure, and may not be considered suitable
[27]
candidates for liver resection . Recent advances in surgical techniques, such as laparoscopic and robotic
approaches, may contribute to reduced surgical morbidity and improved outcomes in selected patients .
[28]
The surgical outcomes of liver resection for liver cirrhosis patients with iCCA have been shown to be
influenced by various factors, such as the extent of liver resection, the presence of microvascular invasion,
[29]
node metastases status, and the tumor differentiation grade . Although liver resection can provide
favorable long-term survival rates in well-selected patients, tumor recurrence remains a significant
challenge . The reported 5-year overall survival rate after liver resection for iCCA in patients with liver
[30]
cirrhosis is approximately 20% [30,31] . The strategy of salvage liver transplantation, which involves conducting
a liver transplant after hepatectomy if cancer recurs, is a concept worth exploring. However, in the context
of iCCA and donor scarcity, further comprehensive investigations are needed to establish the efficacy and
survival benefit of this approach. Moreover, patients with cirrhosis may encounter a higher risk of
postoperative complications, such as liver decompensation, bleeding, and infection, in comparison to non-
cirrhotic patients . Liver resection represents a viable therapeutic option for well-selected liver cirrhotic
[32]
patients with iCCA. On the other hand, numerous decompensated cirrhosis patients with iCCA lack
curative treatment options, even if the tumor is small enough to have a favorable prognosis if completely
removed.

PROGNOSIS OF UNRESECTABLE ICCA PATIENTS
Owing to multiple intrahepatic lesions, local infiltration, lymph node involvement, and distant metastases, a
considerable number of patients are not eligible for operative procedures [4,33] . Reportedly, approximately
60%-70% of iCCA patients present with conditions that are unresectable . Without any form of treatment,
[4]
the median survival time for patients with unresectable iCCA ranges from 2.5 to 7.5 months . The first-
[34]
line chemotherapy for unresectable iCCA, typically comprising gemcitabine and cisplatin, demonstrates
limited effects on overall survival (OS) [35,36] . Although a prior study indicated that GEMOX (gemcitabine