In the intricate landscape of liver diseases, one condition that stands as an enigma is the giant hepatic hemangioma (HH). These massive vascular tumors, characterized by their formidable size, pose unique challenges to patients and healthcare providers alike [1]. Giant HHs are often considered benign, but their huger size and potential complications can make them far from benign in their impact on the lives of those affected [2]. Amid the myriad of treatment options available, liver transplantation (LT) has been performed for HHs that have serious clinical manifestations.

This study reviewed the role of LT as an indication for giant HH. Through an exploration of indications, diagnostic criteria, and the clinical rationale behind this decision, we aim to provide a comprehensive understanding of why LT stands as a pivotal strategy in the management of giant HH.

A meticulous search of the literature was performed for studies published up to September 2023 for cases of patients with giant HH who underwent LT. The literature was searched using search terms as follows in all possible combinations: “liver hemangioma,” “giant hemangioma,” “liver transplantation,” and “Kasabach-Merritt syndrome.” Literature in English was selected. All articles with statement of demographics (age, sex), symptoms, diagnostic evaluation, tumor characteristics (location, histology, size, weight), and post-transplantation outcomes (mortality, length of stay, complications) of patients with giant HH who undergo LT were evaluated.

A total of 18 studies were finally included in the present analysis, which recruited 19 patients, as shown in Table 1 [3-20]. The mean age of patients was 39.9±8.6 years. The most common reported symptoms were abdominal distention, respiratory distress, upper abdominal pain, excessive bleeding, and coagulopathy. Preoperative laboratory tests showed abnormal liver function in all patients (high aspartate transaminase and alanine transaminase levels, low platelet count, prolongation of prothrombin time, and of activated partial thromboplastin time, low fibrinogen, elevated D-dimers). Nine patients were diagnosed with Kasabach-Merritt syndrome.

Table 1 . Collective review of literature on liver transplantation (LT) for giant hepatic hemangioma.

Author (year)	Age (yr)/sex	Pretransplant clinical symptoms	KMS	Hemangioma size (cm)	LT type	Short-term outcome	Re-LT
Zhao et al. (2022) [3]	36/M	Abdominal distention	No	NA	DD	Alive	No
Zhao and Legan (2022) [4]	39/F	Intra-abdominal hemorrhages	Yes	14.3×14.6×14.9	DD	Alive	No
Eghlimi et al. (2020) [5]	38/M	Abdominal distention, leg edema	No	32.4×26×3.1	DD	Alive	No
Lee et al. (2018) [6]	50/F	Upper abdominal pain, abdominal distention	No	16	LD	Alive	No
Lange et al. (2015) [7]	46/F	Abdominal distention	No	21.7×23.7×25.5	DD	Alive	No
Yildiz et al. (2014) [8]	44/F	Abdominal distention, shortness of breath	Yes	22×18×23	DD	Alive	No
Zhong et al. (2014) [9]	27/F	Upper abdominal pain, abdominal distention	No	50×40×25	LD	Alive	No
Unal et al. (2011) [10]	56/F	Upper abdominal pain	Yes	N/A	DD	Alive	No
Vagefi et al. (2011) [11]	32/F	Abdominal distention	Yes	18×23	DD	Alive	No
Aseni et al. (2010) [12]	46/M	Pulmonary thromboembolism	No	N/A	DD	Alive	No
Meguro et al. (2008) [13]	45/F	Abdominal distention	Yes	15	LD	Alive	No
Ferraz et al. (2004) [14]	25/F	Progressive abdominal distention	Yes	46×40×15	DD	Alive	No
Kumashiro et al. (2002) [15]	48/F	Abdominal distension	Yes	N/A	LD	Alive	No
Keegan et al. (2001) [16]	34/M	Respiratory distress, persistent abdominal distention	No	63×45×51	DD	Alive	No
Longeville et al. (1997) [17]	47/M	Excessive bleeding after teeth extraction	Yes	25	DD	Alive	No
Russo et al. (1997) [18]	43/F	Abdominal distension	No	21	DD	Alive	No
Chui et al. (1996) [19]	33/F	Upper abdominal pain, exertional dyspnea	No	N/A	DD	Alive	Yes
	43/F	Gradually enlarged liver during second pregnancy	No	40×35×15	DD	Alive	No
Klompmaker et al. (1989) [20]	27/M	Hepatomegaly	Yes	N/A	LD	Alive	No

KMS, Kasabach-Merritt syndrome; DD, deceased donor; LD, living donor; M, male; F, female; N/A, not available..

Concerning the type of liver graft, 14 patients received transplant from deceased donors whereas the remaining 5 patients underwent living donor LT. No intraoperative or postoperative 90-day mortality following LT was documented. All abnormal blood parameters returned to normal within few days postoperatively in all patients. Complications were encountered in 5 patients of the involved patients. Of these, 2 patients required re-operation; abdominal bleeding was detected in one patient and successfully controlled; and the other patient required re-transplantation due to acute liver rejection. All patients were alive at the time of their documentation.

The most effective approach to addressing giant HH remains a subject of ongoing investigation. In instances where giant HHs remain asymptomatic, a conservative management approach may be considered, with vigilant monitoring until symptoms or complications manifest [21]. Surgical intervention becomes necessary when symptoms or complications develop, and the two primary surgical techniques employed include resection or enucleation of the lesion. Alternatively, less invasive methods such as transarterial embolization of the feeding artery and radiofrequency ablation have been proposed as potential strategies to induce a reduction in the size of giant LHs [22].

LT for giant HHs is a rare and extreme measure and is usually not recommended as the first-line treatment. The decision to perform LT for giant HH is usually made on a case-by-case basis after thorough evaluation by multidisciplinary team of medical experts. The primary indications for LT are generally related to life-threatening complications or symptoms that cannot be managed by other means. When a giant HH causes life-threatening symptoms such as severe abdominal pain, hemorrhage, or rupture, and these symptoms cannot be controlled or managed through other means, LT may be considered. If giant HHs lead to complications like Kasabach-Merritt syndrome, uncontrolled bleeding, or compression of adjacent organs to the extent that it compromises their function, LT may be indicated. In instances where a giant HH exhibits rapid growth despite attempts at conservative management or other interventions, LT might be considered as a last resort to control the tumor’s progression. In addition, severe, unmanageable pain related to the giant HH that significantly impairs the patient’s quality of life and cannot be relieved by other therapeutic modalities may be an indication for LT [4-7]. In the present study, the main indications for LT included symptoms related to size of HH (respiratory distress, abdominal discomfort, and pain), risk of rupture, coagulopathy (Kasabach-Merritt syndrome, disseminated intravascular coagulation), and the failure of previous interventions (embolization, resection) to control the disease.

Kasabach-Merritt syndrome is a consumptive coagulopathy associated with the presence of a large vascular lesion. It is often a frustrating condition to treat and it carries a high mortality rate [4,23]. Nine out of 19 patients in the present study had suffered from Kasabach-Merritt syndrome, and all of them survived after LT.

Considering that LT for giant HH is a rare and controversial procedure, it is difficult to clearly describe the post-transplant survival because it can vary widely depending on the individual patient’s condition, the extent of the tumor, the presence of complications, and the overall health of the patient as well as the skill and experience of the surgical and medical teams involved. LT is a procedure can be life-saving, and patients may experience long-term survival.

The majority (14 of 19) of patients undergoing LT for giant HH have received deceased donor LT in the present study. There are only five cases of living donor LT for giant HH worldwide [6,9,13,15,20]. Patients with giant HH maintain relatively stable liver function profiles, often resulting in low Model for End-stage Liver Disease scores. Given the exceptionally limited availability of deceased donor LT in the current setting of Korea, it becomes imperative to grant priority to patients with giant HH for living donor LT [24]. To the best of our knowledge, a few cases of living donor LT have been performed in patients with giant HH, but only one case was reported in literature to date [6].

In conclusion, LT is a safe and effective treatment option in the management of symptomatic or complicated giant HH in selected patients.

There was no funding related to this study.

All authors have no conflicts of interest to declare.

Conceptualization: CSP. Data curation: CSP. Formal analysis: All. Investigation: All. Methodology: CSP, YKC. Supervision: CSP. Validation: YKC. Visualization: YKC. Writing – original draft: All. Writing – review & editing: All.