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Page 2 of 9 Akabane et al. Hepatoma Res 2023;9:29 https://dx.doi.org/10.20517/2394-5079.2023.45

INTRODUCTION
In recent years, the landscape of liver transplantation for treating intrahepatic cholangiocarcinoma (iCCA)
has undergone significant changes. iCCA, a primary liver malignancy, constitutes the second most common
form of liver cancer, accounting for 10%-15% of all primary liver malignancies . Its incidence has
[1-3]
[4]
consistently risen worldwide, posing a considerable challenge to healthcare systems . Despite advances in
surgical techniques and systemic therapies, the prognosis for patients with iCCA remains unfavorable,
particularly for patients who cannot be a candidate for curative resection due to background liver cirrhosis
[5,6]
or advanced stages of the disease . Liver transplantation has emerged as a potential therapeutic option for
a subset of these patients, offering an opportunity for long-term survival and improved quality of life .
[7-9]
Traditionally, liver transplantation has been considered a contraindication for iCCA, due to the high
recurrence rates and poor post-transplant outcomes associated with this malignancy [10,11] . Nonetheless,
accumulating evidence from recent studies has led to a paradigm shift in the management of iCCA, with
liver transplantation increasingly recognized as a viable option for select patients . This change has been
[3,8]
driven primarily by the identification of acceptable post-transplant outcomes in incidentally discovered
small iCCA in explant pathology , as well as the development of effective neoadjuvant treatment capable of
[7]
controlling advanced iCCA .
[9]
However, the role of liver transplantation in the management of very early or advanced iCCA remains a
subject of ongoing debate and investigation. While two studies have reported encouraging outcomes
[7,8]
following transplantation for early-stage iCCA , there are concerns about the potential risk of tumor
recurrence and the allocation of scarce donor organs to this patient population. Moreover, the optimal
selection criteria and treatment strategies for patients with advanced iCCA have yet to be established. In this
context, this review aims to provide a current synthesis of the evidence regarding the role of liver
transplantation in managing very early or advanced iCCA, as well as to discuss the key challenges and
future directions in this rapidly evolving field.

LIVER CIRRHOSIS PATIENTS WITH INTRAHEPATIC CHOLANGIOCARCINOMA
Liver cirrhosis, a consequence of chronic liver injury, is characterized by fibrosis, nodule formation, and
subsequent loss of liver function, predisposing patients to the development of primary liver malignancies .
[12]
iCCA is known to arise in the context of liver cirrhosis in a subset of patients, with the prevalence of
cirrhosis in iCCA patients ranging from 20% to 50% [13,14] . The population of liver cirrhosis patients with
iCCA exhibits specific characteristics in terms of etiology, clinical presentation, and prognosis compared to
non-cirrhotic patients with iCCA. The etiology of liver cirrhosis in iCCA patients is often multifactorial,
with several risk factors contributing to its development. Common etiologies include chronic viral hepatitis
(hepatitis B and C), alcohol-induced liver disease, nonalcoholic steatohepatitis (NASH), primary sclerosing
cholangitis (PSC), and certain metabolic disorders [15,16] . Viral hepatitis, in particular, has been identified as a
[17]
significant risk factor for iCCA in cirrhotic patients .

Differentiating hepatocellular carcinoma (HCC) and iCCA in a cirrhotic liver poses a diagnostic challenge.
The mainstay for this diagnosis hinges on imaging techniques. HCC, which originates from hepatocytes,
often demonstrates an arterial enhancement pattern. In contrast, iCCA, stemming from hepatic
parenchyma and showcasing desmoplastic features, relies primarily on the portal system for its blood
supply. Consequently, iCCA is often characterized by a peripheral rim-like contrast enhancement during
arterial and portal phases, with a more attenuated center during the delayed phase [18,19] .