Liver transplantation in a patient with metastatic hepatocellular carcinoma after downstaging with single-agent immunotherapy: the first case report
Case Report

Liver transplantation in a patient with metastatic hepatocellular carcinoma after downstaging with single-agent immunotherapy: the first case report

Angelo Pirozzi1,2,3, Celine Hoyek3, Oluseyi Abidoye3, Naohiro Okano3,4, Michelle C. Nguyen5, Thomas Byrne6,7, Bashar Aqel6,7, David Chascsa8,9, Sadeer Alzubaidi10, Lorenza Rimassa1,2, Tanios Bekaii-Saab3, Mitesh J. Borad3

1Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; 2Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Italy; 3Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Phoenix, AZ, USA; 4Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan; 5Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Scottsdale, AZ, USA; 6Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Phoenix, AZ, USA; 7Transplant Center, Mayo Clinic Arizona, Phoenix, AZ, USA; 8Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA; 9Transplant Center, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA; 10Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ, USA

Contributions: (I) Conception and design: MJ Borad, A Pirozzi; (II) Administrative support: MJ Borad; (III) Provision of study materials or patients: MJ Borad, O Abidoye; (IV) Collection and assembly of data: A Pirozzi, C Hoyek; (V) Data analysis and interpretation: A Pirozzi, MJ Borad, L Rimassa; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Mitesh J. Borad, MD. Division of Hematology and Medical Oncology, Mayo Clinic Arizona, 5779 E. Mayo Blvd., Phoenix, AZ 85054, USA. Email: borad.mitesh@mayo.edu.

Background: Immunotherapy in hepatocellular carcinoma (HCC) has changed the clinical practice for unresectable and advanced setting after the approvals of atezolizumab plus bevacizumab and durvalumab plus tremelimumab (STRIDE regimen). A growing field for its application is the use of systemic therapy to achieve disease control in patients already listed for liver transplantation (LT) (bridging therapy) and fitting those not eligible within the LT criteria (conversion therapy). However, there is still a lack of prospective data for using immune checkpoint regimens in this setting, especially regarding the treatment-free interval before LT which may be different based on the immunotherapy drug chosen. Here, we present the first case in the literature of a patient with metastatic extrahepatic disease [Barcelona Clinic Liver Cancer (BCLC)-C] and severe alcoholic cirrhosis who successfully LT after a prolonged radiologic complete response (CR) to single-agent immunotherapy.

Case Description: A 61-year-old man with a diagnosis of advanced hepatocellular carcinoma (aHCC) (abdominal lymph nodes, lung, mediastinal nodes, bone) in the setting of alcoholic cirrhosis with a history of esophageal varices was treated with single-agent nivolumab 480 mg intravenous (IV) every four weeks for approximately 17 months (18 cycles) with partial response (PR). Considering the prolonged disease control, systemic therapy was discontinued. Three months after the treatment stopped, a new hepatic lesion was detected on abdominal magnetic resonance imaging (MRI). The new hepatic lesion was treated with microwave ablation (MWA) with a CR. After 10 months from MWA, the patient was free of active disease in the context of a slow, delayed response to immunotherapy. With the aim to treat his underlying liver disease, the patient received orthotopic LT, and he is currently free of cancer after one year of follow-up.

Conclusions: LT in patients with aHCC with CR to immunotherapy may be feasible and safe in carefully selected patients, potentially curing the underlying liver disease, which impacts both survival and quality of life. However, the immunosuppressive state induced by LT may facilitate the disease progression of extrahepatic disease, therefore this should be considered only in selected patients with a prolonged CR to systemic therapy.

Keywords: Liver transplantation (LT); hepatocellular carcinoma (HCC); immunotherapy; case report; metastatic disease

Submitted Oct 17, 2024. Accepted for publication Feb 19, 2025. Published online Jun 26, 2025.

doi: 10.21037/jgo-24-764

Highlight box

Key findings

• Liver transplantation (LT) may be considered in carefully selected patients with advanced hepatocellular carcinoma (aHCC) and extrahepatic disease with a prolonged complete response to immune checkpoint inhibitors (ICIs).

• The washout period recommended should be ≥90 days.

• The use of ICIs in combination regimens seems a reasonable option for downstaging therapy in aHCC with extrahepatic disease, even with the limit of extremely poor evidence in this setting.

What is known and what is new?

• LT is allowed only in very early and early stage [Barcelona Clinic Liver Cancer (BCLC)-0 and BCLC-A] HCC within Milan criteria or extended transplantation criteria.

• Ongoing trials are assessing the use of systemic treatment, especially immunotherapy, as a downstaging strategy to fit ineligible patients within transplantation criteria.

What is the implication and what should change now?

• This is the first case of a successful LT in a patient with metastatic extrahepatic HCC after a prolonged response to immunotherapy.

• LT may be considered for highly selected patients with metastatic extrahepatic HCC who achieve a prolonged clinical response to immunotherapy.

Introduction

Hepatocellular carcinoma (HCC) is the most representative subtype of primary liver cancer, accounting for 75–85% of all cases, with a trend towards an increase in both incidence and mortality (1). Currently, 5-year overall survival (OS) is still poor (~19.6%) due to the high rate of relapse and diagnosis when the disease is already unresectable HCC (uHCC) or advanced HCC (aHCC) (2). The use of immune checkpoint inhibitor combinations for uHCC/aHCC was supported by the positive outcomes from the phase III trials, IMbrave150, HIMALAYA and CheckMate 9DW. However, the treatment associated with the highest 5-year OS rate (70–80%) and median OS (158 months) is still, by far, liver transplantation (LT) (3) whose use is limited to very early stage [Barcelona Clinic Liver Cancer 0 (BCLC-0)] and early stage (BCLC-A) HCC within the Milan criteria (MC) and extended criteria (4,5) (Table 1). There are still no standardized guidelines in terms of systemic therapy application for this setting, especially regarding the use of immunotherapy for disease control in patients on the waiting list for LT (bridging strategy) or for reducing tumor burden (downstaging strategy) enabling those beyond the LT criteria to receive liver graft (6). This uncertainty is mainly due to the paucity of published data from prospective studies. In addition, the intrinsic challenge of stimulating the immune system against cancer cells and avoiding allogenic reactions, potentially deadly, is still far from being solved (7). Herein we describe the first case in the literature of a patient with metastatic extrahepatic disease who achieved a complete response (CR) and underwent LT without disease relapse after one year from liver grafting. We present this case in accordance with the CARE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-764/rc).

Table 1

Overview of criteria for liver transplantation

Criteria for liver transplantation Number of lesions and diameter Vascular invasion Extra-hepatic disease
Milan criteria Single lesion ≤5 cm or up to 3 lesions each ≤3 cm No No
UCSF Single lesion ≤6.5 cm or ≤3 lesions with the largest being ≤4.5 cm No No
Up-to-7 7 cm as the sum of the size of the largest tumor and the number of tumors No No
Toronto Any tumor size or number. All lesions require a liver biopsy and must show poor differentiation No No
UNOS Single lesion >5 cm but ≤8 cm No No
2–3 lesions each ≤5 cm with total diameter of all lesions ≤8 cm
4–5 lesions each ≤3 cm with total diameter of all lesions ≤8 cm

Adapted with permission from (5) under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by-nc/4.0/). UCSF, University of California, San Francisco; UNOS, United Networking for Organ Sharing.

Case presentation

A 61-year-old man with an oncology history of BCLC-A HCC along with alcoholic cirrhosis and metabolic dysfunction-associated steatotic liver disease (MASLD) presented to Mayo Clinic Arizona due to local and distant progressive disease. His medical history was notable for hypertension and diabetes mellitus type 2. He had required transjugular intrahepatic portosystemic shunt (TIPS) due to refractory ascites, and a 10-year history of esophageal varices with multiple bleeding episodes. The patient had received treatment with transarterial radioembolization (TARE) without complications, 4 months prior to receiving systemic therapy. The response was evaluated with magnetic resonance imaging (MRI) of the abdomen with contrast detecting growth of the pretreated hepatic lesion (8 vs. 6.9 cm), marked progression of a known occlusive tumor thrombus of the portal vein extending to the vein confluence, newly enlarged pre-celiac and portocaval lymph nodes as well as the onset of multiple extrahepatic lesions (single lung nodule, mediastinal nodes, bone lesions of T10 vertebra and bilateral sacral ala). He denied significant symptoms except for decreased libido. Physical examination was negative at the time of progression. The most recent laboratory results showed preserved liver function (Child-Pugh A), and alpha-fetoprotein (AFP) was 788 ng/mL. Current medications included lactulose, nadolol, rifaximin, spironolactone pantoprazole, lisinopril, linagliptin, metformin. Based on the disease extent, the patient would have been a suitable candidate for first-line systemic treatment with the combination of atezolizumab and bevacizumab. However, due to the high risk of bleeding associated with bevacizumab in patients with a history of variceal bleeding, single-agent immunotherapy with nivolumab was preferred. Nivolumab was administered 480 mg intravenous (IV) every 4 weeks for approximately 17 months (18 cycles) with a partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria that was attained after the first 2 months of treatment. The dominant hepatic lesion had shrinkage (6.9 vs. 8.0 cm) along with regression of the associated portal vein tumor thrombus and other sites of disease. In details, there was reduction in the size of para-aortic lymph nodes (4.5 vs. 11 mm), right lower paratracheal lymph node (8.0 vs. 11 mm), celiac lymph node (2.0 vs. 4.6 cm), and mediastinal lymph node adjacent to the right lung fissure (14 vs. 20 mm) (Figure 1A,1B). There was a slight increase in both the T10 lesion (2.1 vs. 1.7 cm) and lesions in the sacrum by MRI assessment. Five months after the immunotherapy start, the patient developed severe ascites with increased body weight (>10 kg), for which a therapeutic paracentesis was performed with clinical benefit. However, work up showed a persistently worsening liver function, with increasing bilirubin (3.3 vs. 2.0 mg/dL) and decreasing albumin (2.8 vs. 3.0 g/dL). At that juncture, the patient had a Child-Pugh score of B9, which constituted a relative contraindication for continuation of immunotherapy. However, given the robust radiologic response, the patient remained on immunotherapy, maintaining disease control for ≥1 year without further worsening of liver function. Considering the durable response to therapy, nivolumab treatment was discontinued, with close imaging surveillance every 2–3 months. A solitary hepatic lesion with largest diameter of 1.6 cm was found on imaging 3 months after stopping nivolumab. After discussing the case with the multidisciplinary team (MDT), the patient underwent microwave ablation (MWA) therapy with CR of the hepatic lesion after 3 months from the procedure. Of note, the radiologic assessment showed no sign of active cancer in other locations (Figure 1C). After 10 additional months of disease control, the case was rediscussed with the MDT with the indication for LT due to the high risk for liver decompensation-related death, even though the tumor burden was largely outside LT criteria given that the baseline largest lesion was ≥8.1 cm with the presence of concomitant portal vein involvement as well as extrahepatic disease. The donor liver was obtained from a deceased donor following cardiac death. Pathological evaluation of the explanted liver was positive for the presence of multifocal mass-forming areas of infarction and post-treatment changes together with a single 1.7 cm viable G2 lesion and organizing portal vein thrombus, all surgical margines were negative, no sign of vascular invasion detected, no lymph nodes were collected (stage pT1aNxMxR0). An immunosuppressive regimen of tacrolimus (4 mg twice daily), mycophenolate mofetil (1 g twice daily), and prednisone (25 mg twice daily) was initiated, with mycophenolate mofetil subsequently reduced to 180 mg twice daily and prednisone gradually tapered over 1 month. Two months after starting this regimen, the patient was transitioned from tacrolimus to everolimus due to the onset of severe headaches. Additionally, the patient received infection prophylaxis with acyclovir (400 mg twice daily) for 1 month, trimethoprim/sulfamethoxazole (160 mg/800 mg once daily) for 6 months, and fluconazole (200 mg once daily). A high-risk surveillance protocol was set due to the high burden of disease at the time of initial diagnosis, consisting of a follow-up made of chest computed tomography (CT) scan and abdomen MRI done at 4, 8, 12, 18, 24, 30, and 36 months post-transplantation. After 1 year since the LT, the patient has no evidence of recurrence and denies significant issues except for a chronic headache he has had since LT was done. A visual timeline summary and AFP trend are provided (Figures 2,3). Brain MRI did not show the presence of metastatic disease. The main complication of LT was biliary stricture, causing repetitive episodes of cholangitis. He is on the high-risk surveillance protocol described in detail previously.

Figure 1 CT and MRI scans of disease sites (yellow arrows) and radiologic treatment response. (A) Baseline liver lesions, mediastinal nodes and vertebral lesion. (B) Partial response at the first radiologic assessment during immunotherapy. (C) Complete response. CT, computed tomography; MRI, magnetic resonance imaging.
Figure 2 Visual timeline of clinical events. HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging; MWA, microwave ablation; SIRT, selective internal radiation therapy; TIPS, transjugular intrahepatic portosystemic shunt.
Figure 3 AFP blood level trend during patient treatment. The x-axis represents the time from the start of immunotherapy, and the y-axis represents the AFP value. AFP, alpha-fetoprotein; FU, follow-up; LT, liver transplant.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Oral informed consent for publication of this case report and accompanying images was obtained from the patient.

Discussion

To our knowledge, this is the first case reported of a patient with metastatic HCC to achieve a successful downstaging and receiving an LT with an optimal outcome at the last follow-up, except for recurrent biliary tract obstructions, which were promptly and successfully addressed. American Association for the Study of Liver Disease (AASLD) guidelines recommend the use of locoregional therapy [MWA, transarterial chemoembolization (TACE), TARE, external beam radiotherapy (EBRT)] for bridging and downstaging therapy all in the setting of patients with disease limited to the liver (BCLC 0–B) (8). However, they do not recommend the routine use of systemic therapy in the metastatic setting due to the lack of data, the high likelihood of disease progression and the correlated risks for the use of immunotherapy that need to be considered (9). Firstly, the immunosuppression state induced by LT surgery and immunosuppressive regimens following the procedure may favor immune escape of occult metastases and, ultimately, a rapid tumor progression. LT surgery, especially, has been known to potentially increase the proliferation of T regulatory (T-reg) cells, considered the main actors of immune tolerance, through blood loss, infection and hypothermia (10). Simultaneously, the use of immune suppressors such as steroids, calcineurin inhibitors (tacrolimus, sirolimus, everolimus), and antimetabolites (mycophenolic acid) may impair T-cell effectors response against cancer, which comprises the key mechanism for immunotherapy. Secondly, the risk of both acute and chronic rejection may be higher in patients receiving immune checkpoint inhibitors (ICIs) due to allograft immune reaction (11). The first use of nivolumab in the pre-transplanted setting resulted in acute hepatic necrosis on the third day postoperative (POD) with unsuccessful use of high-dose immunosuppression (methylprednisolone 1 g/day and 1.5 mg/kg rabbit thymocyte globulin q24h) and supportive therapy (12). Similar outcomes were reported by Wassmer et al., showing that the most common ICI used in the preclinical setting up to May 2023 was nivolumab, and it was also the one most highly related to allograft reactions (13).

However, all reported allograft rejections following immunotherapy shared a washout period of 8–93 days between the last dose of ICI and the time of LT (Table 2). Results from a systematic review published in 2021 confirmed the risk of rejection is linked to the duration of time between LT and ICI, emphasizing the importance of defining the optimal period to tackle alloimmune reactions and graft loss onset (34). Based on these data and previous case series, a washout period of >90 days is broadly considered to be the safest to decrease the risk of alloimmune reactions and graft loss (13,35,36). In addition, the use of bevacizumab is associated with a significant risk of bleeding and dehiscence if not stopped at least 6–8 weeks before liver surgery for patients with metastatic colorectal cancer candidate to liver resection, which likely should be applied even to patients with HCC (37). Thirdly, treatment-related adverse events (trAEs) may potentially compromise the eligibility of patients who are still within LT criteria, especially when using the main immunotherapy combinations currently approved across the world. Several trials are ongoing trying to understand the feasibility of systemic therapy as a safe and effective bridging and downstaging strategy; among them, worthy mentions are the ImmunoXXL trial (NCT05879328) and the VITALITY study. The VITALITY study is the first multiregional study in the United States (2016–2023) including 117 consecutive HCC patients evaluated for LT and treated preoperatively with ICIs. Of these patients, 86 (73.5%) had disease beyond MC, and 65 (75.6%) were successfully downstaged. A total of 43 patients (36.7%) underwent transplantation, including 18 (15.4%) who were within MC and 23 (19.7%) who were initially beyond those criteria. In the entire cohort, 94% received both ICIs and locoregional therapies. There were no G4/G5 trAEs while patients were on the transplant waiting list. The 3-year intention-to-treat survival rate was 71.1%, with 73.5% survival in those within MC and 69.7% in those beyond (P=0.329). Seven patients experienced post-transplant rejection, six of whom had received their last dose of ICI within 3 months prior to LT, leading to one case of graft loss (38). Finally, The PLENTY trial (NCT04425226) and the ESR-20-21010 (NCT05027425) are other prospective studies assessing the use of the STRIDE regimen and pembrolizumab in the same setting (39). However, one of these trials include patients with extrahepatic disease.

Table 2

Summary of cases receiving ICIs pre-transplantation reported in literature

Study Study type Number of patients receiving ICIs pre-transplantation [rejections] Age (years)/sex Underlying liver disease ICI Duration Washout period (days) Rejection proved by biopsy Retransplantation Postoperative follow-up (expressed as median for some case series)
Nordness 2020 (14) Case report 1 [1] 65/M HCV Nivolumab 24 months 8 POD6 and death No NA
Schwacha-Eipper 2020 (15) Case report 1 [0] 62/M ALD Nivolumab 34 cycles 105 No rejection No 12 months
Aby 2022(16) Case report 1 [1] 64/M HCV Nivolumab 23 months 16 POD9 No, high-dose corticosteroids 16 months
Chen 2021 (17) Case report 1 [1] 39/M HBV Toripalimab 10 months 93 POD2 and deceased at POD3 No NA
Chen 2021 (18) Case series 5 [0] Mean age 53.2±5.4 (SD)/4 M, 1 F NA Nivolumab NA 63.8±18.3 No No 12 months
Dehghan 2021 (19) Case report 1 [1] 60/F HCV Nivolumab 15 months 35 POD10 Yes, POD 34 18 months
Lizaola-Mayo 2021 (20) Case report 1 [0] 63/M NASH Nivolumab plus ipilimumab 6 months 56 No rejection No 6 months
Peterson 2021 (21) Case report 1 [0] 68/M HCV Nivolumab 6 months 300 No rejection No 7 months
Qiao 2021 (22) Case series 7 [1] Mean age 53±12.1 (SD)/7 M HCV Pembrolizumab or camrelizumab NA 40 on average POD11 No, use of corticosteroids NA
Sogbe 2021 (23) Case report 1 [0] 61/M HBV Durvalumab 18 months 92 No rejection No 24 months
Tabrizian 2021 (24) Case series 9 [2] Mean age 57±11.4 (SD)/3 M, 6 F 5 HBV Nivolumab 13±10.57 cycles 16.44±5.9 No No 16 months
2 HCV
1 NASH
1 unknown
Abdelrahim 2022 (25) Case report 1 [0] 66/M HCV Atezolizumab plus bevacizumab 4 months 60 No rejection No >12 months
Dave 2022 (26) Case series 5 [2] Mean age 61±6.52 (SD)/NA NA Nivolumab NA 2 cases <90 with rejection Yes For both patients with rejection with death of one of them 2 months after transplantation NA
NA 3 cases >90 without rejection NA
Schnickel 2022 (27) Case series 5 [2] Mean age 66±3.74 (SD)/3 M, 2 F 4 HCV Nivolumab 11.6±4.09 87±67.78 POD14 No, use of corticosteroids 13 (range, 2–38) months
1 HBV <POD14 No, use of rATG, rituximab, and IVIGs
Kang 2022 (12) Case report 1 [0] 14/M None Pembrolizumab 3 months 138 No No 96 months
Yin 2022 (28) Case report 1 [0] 37/M HBV Pembrolizumab and lenvatinib 12 months <30 POD0 No 2 days
Chouik 2023 (29) Case report 1 [0] 57/M ALD Atezolizumab plus bevacizumab 12 months 60 No rejection No 15 months
Ohm 2023 (30) Case series 3 [0] Mean age 54.33±15.82 (SD)/3 M HCV Atezolizumab plus bevacizumab 5 months 229 No rejection No 24 months
HCV Atezolizumab plus bevacizumab 4 months 2 22 months
HCV Nivolumab plus ipilimumab 2 months 7 18 months
Rudolph 2023 (31) Case series 1 [0] 47/F None Nivolumab 7 months 55 – No 48 months
Schmiderer 2023 (32) Case report 1 [0] 63/M HCV Atezolizumab plus bevacizumab 6 months 42 No rejection No NA
Wang 2023 (33) Case series 16 [9] Mean age 50.93±8.9 (SD)/14 M, 2 F 14 HBV 2 nivolumab, 7 pembrolizumab, 4 sintilimab, 2 camrelizumab, and 1 multiple ICIs (nivolumab, toripalimab, sintilimab, and tislelizumab) 6 (range, 1–27) cycles 40.5 (range, 7–184) Median time of rejection POD7 Yes, 2 cases with subsequent mild rejections 352.5 months
2 ALD

Adapted with permission from (13) under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). ALD, alcoholic liver disease; F, female; HBV, hepatitis B virus; HCV, hepatitis C virus; ICI, immune checkpoint inhibitor; IVIGs, intravenous immunoglobulins; M, male; NA, not available; NASH, nonalcoholic steatohepatitis; POD, postoperative day; rATG, rabbit antithymocyte globulin; SD, standard deviation.

Conclusions

LT may be a feasible option for highly selected patients with metastatic HCC who achieve a prolonged clinical response to immunotherapy. Our patient with metastatic HCC received LT 15 months after the last dose of nivolumab, confirming the importance of adherence to a washout period of >90 days. In addition, he received a standard immunosuppressive therapy after LT, which did not impact disease relapse, considering a progression-free survival of one year at the last follow-up. Individualized factors such as type of response, duration of response, a washout period of >90 days, baseline liver disease, liver function, and patient characteristics should drive decision-making for this category of patients. Nonetheless, an MDT is recommended to properly balance the risk of distant relapse with the potential to cure a patient’s liver disease, ultimately improving survival and quality of life.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-764/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-764/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-764/coif). N.O. reports receiving honoraria from Taiho Pharmaceutical, Eisai, Bayer Yakuhin, Chugai Pharma, Ono Pharmaceutical, Daiichi Sankyo, AstraZeneca, Nihon Servier, Incyte, and MSD. S.A. reports receiving consulting fees from Penumbra, Boston Sci, and Techsomed; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and holding a stock in Techsomed. L.R. reports grant/research funding (to institution) from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, IPSEN, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, TransThera Sciences, and Zymeworks; consulting fees from AbbVie, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, IPSEN, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, and Zymeworks; lecture fees from AstraZeneca, Bayer, Bristol Myers Squibb, Guerbet, Incyte, IPSEN, Roche, and Servier; and travel expenses from AstraZeneca. T.B.S. reports receiving consulting fees from Servier, Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai, Merus, Merck KGaA, and Merck (to institution), Stemline, AbbVie, Blueprint Medicines, Boehringer Ingelheim, Janssen, Daiichi Sankyo, Natera, TreosBio, Celularity, Caladrius Biosciences, Exact Science, Sobi, Beigene, Kanaph, Astra Zeneca, Deciphera, Zai Labs, Exelixis, MJH Life Sciences, Aptitude Health, Illumina, Foundation Medicine and Sanofi, Glaxo SmithKline, Xilio (to self); patents issued for human pd1 peptide vaccines and uses thereof: methods and compositions for the treatment of cancer cachexia; participating on a Data Safety Monitoring Board or Advisory Board for The Valley Hospital, Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Merck/Eisai, PanCan and 1Globe; has a license from Uptodate and leadership or fiduciary role in Imugene, Immuneering, Xilis, Replimune, Artiva and Sun Biopharma. M.J.B. receives grant support from Relay Pharmaceuticals, Taiho, Basilea, Novartis, Incyte and Kinnate. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Oral informed consent for publication of this case report and accompanying images was obtained from the patient.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Pirozzi A, Hoyek C, Abidoye O, Okano N, Nguyen MC, Byrne T, Aqel B, Chascsa D, Alzubaidi S, Rimassa L, Bekaii-Saab T, Borad MJ. Liver transplantation in a patient with metastatic hepatocellular carcinoma after downstaging with single-agent immunotherapy: the first case report. J Gastrointest Oncol 2025;16(3):1321-1330. doi: 10.21037/jgo-24-764

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