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Zhang S, Zhang S. Successful Liver Transplantation After Achieving Complete Clinical Remission of Hepatocellular Carcinoma With Combination Therapy of Immune Checkpoint Inhibitors and Targeted Agents: A Case Report. Transplant Proc 2025; 57:580-584. [PMID: 40087050 DOI: 10.1016/j.transproceed.2025.02.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 02/26/2025] [Indexed: 03/16/2025]
Abstract
Immunotherapy, primarily with immune checkpoint inhibitors, has become pivotal in the treatment of advanced hepatocellular carcinoma (HCC), leading to significant tumor burden reduction. However, its applicability in liver transplantation remains controversial. Due to the potential risks of rejection limiting large-scale clinical trials and the incomplete understanding of underlying mechanisms, whether transplant recipients can benefit from immunotherapy remains uncertain. This report describes the application of immunotherapy in liver transplantation, wherein two patients achieved complete tumor remission after receiving immunotherapy combined with other treatments before transplantation, enabling successful liver transplantation surgeries. Additionally, one patient received combination therapy with tislelizumab and lenvatinib before transplantation (Case 2), representing the first reported case utilizing this combination therapy as a bridging treatment before LT.
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Affiliation(s)
- Shaobo Zhang
- Graduate School of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui, China; Department of Liver Transplantation, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Shugeng Zhang
- Graduate School of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui, China; Department of Liver Transplantation, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
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2
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Zhang YJ, Zhou DJ, Li H, Pan Q, Cheng Y. Prolongated and large dose of r-ATG relieves PD-L1 inhibitor-induced allograft rejection in liver transplant recipient. Hepatobiliary Pancreat Dis Int 2025; 24:221-224. [PMID: 38845248 DOI: 10.1016/j.hbpd.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 05/06/2024] [Indexed: 03/22/2025]
Affiliation(s)
- Yi-Jie Zhang
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Dian-Jie Zhou
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Hong Li
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Qi Pan
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Ying Cheng
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
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Silver CR, De la Garza-Ramos C, Stauffer JA, Majeed U, Wang J, Toskich BB. Ipilimumab and nivolumab plus radioembolization as salvage therapy for atezolizumab and bevacizumab refractory hepatocellular carcinoma resulting in complete pathologic response. Radiol Case Rep 2024; 19:5024-5028. [PMID: 39247469 PMCID: PMC11378113 DOI: 10.1016/j.radcr.2024.07.157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 09/10/2024] Open
Abstract
Unresectable hepatocellular carcinoma unresponsive to first-line immunotherapy has a poor prognosis with modest response to tyrosine kinase inhibitors in the second line. In these patients, the benefit of local therapy with immunotherapy rechallenge is unknown. Radioembolization is a guideline-supported locoregional therapy for HCC that has shown the potential for synergy in combination with immunotherapy. This report describes a patient with veno-invasive HCC and extrahepatic invasion of the right kidney which progressed on atezolizumab and bevacizumab and was subsequently downstaged to resection with ipilimumab and nivolumab plus radioembolization yielding a complete pathologic response. The patient is currently more than 2 years since diagnosis without evidence of disease recurrence.
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Affiliation(s)
- Claudia R Silver
- Florida State University College of Medicine, Tallahassee, Florida
| | | | - John A Stauffer
- Department of Surgery, Mayo Clinic Florida, Jacksonville, Florida
| | - Umair Majeed
- Department of Hematology Oncology, Mayo Clinic Florida, Jacksonville, Florida
| | - Jianfeng Wang
- Department of Hematology Oncology, Pearlman Comprehensive Cancer Center at South Georgia Medical Center, Valdosta, Georgia
| | - Beau B Toskich
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
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Zhong D, Shi Y, Ma W, Liang Y, Liu H, Qin Y, Zhang L, Yang Q, Huang X, Lu Y, Shang J. Single-cell profiling reveals the metastasis-associated immune signature of hepatocellular carcinoma. Immun Inflamm Dis 2024; 12:e1264. [PMID: 38780041 PMCID: PMC11112628 DOI: 10.1002/iid3.1264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 05/25/2024] Open
Abstract
AIM Metastasis is the leading cause of mortality in hepatocellular carcinoma (HCC). The metastasis-associated immune signature in HCC is worth exploring. METHODS Bioinformatic analysis was conducted based on the single-cell transcriptome data derived from HCC patients in different stages. Cellular composition, pseudotime state transition, and cell-cell interaction were further analyzed and verified. RESULTS Generally, HCC with metastasis exhibited suppressive immune microenvironment, while HCC without metastasis exhibited active immune microenvironment. Concretely, effector regulatory T cells (eTregs) were found to be enriched in HCC with metastasis. PHLDA1 was identified as one of exhaustion-specific genes and verified to be associated with worse prognosis in HCC patients. Moreover, A novel cluster of CCR7+ dendritic cells (DCs) was identified with high expression of maturation and migration marker genes. Pseudotime analysis showed that inhibition of differentiation occurred in CCR7+ DCs rather than cDC1 in HCC with metastasis. Furthermore, interaction analysis showed that the reduction of CCR7+ DCs lead to impaired CCR7/CCL19 interaction in HCC with metastasis. CONCLUSIONS HCC with metastasis exhibited upregulation of exhaustion-specific genes of eTregs and inhibition of CCL signal of a novel DC cluster, which added new dimensions to the immune landscape and provided new immune therapeutic targets in advanced HCC.
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Affiliation(s)
- Deyuan Zhong
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
- School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuanChina
| | - Ying Shi
- School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuanChina
| | - Wenzhe Ma
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and TechnologyMacau SARChina
| | - Yuxin Liang
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
- School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuanChina
| | - Hanjie Liu
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
| | - Yingying Qin
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
| | - Lu Zhang
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
| | - Qinyan Yang
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
| | - Xiaolun Huang
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
- School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuanChina
| | - Yuanjun Lu
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
| | - Jin Shang
- Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduChina
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Pahari H, Raj A, Sawant A, Ahire DS, Rathod R, Rathi C, Sankalecha T, Palnitkar S, Raut V. Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040? World J Transplant 2024; 14:88833. [PMID: 38576752 PMCID: PMC10989470 DOI: 10.5500/wjt.v14.i1.88833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 12/21/2023] [Accepted: 01/22/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.
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Affiliation(s)
- Hirak Pahari
- Department of Liver Transplant and HPB Surgery, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Amruth Raj
- Department of Liver Transplant and HPB Surgery, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Ambreen Sawant
- Department of Liver Transplant Anaesthesia, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Dipak S Ahire
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Navi Mumbai 410210, India
| | - Raosaheb Rathod
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Chetan Rathi
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Aurangabad 431003, India
| | - Tushar Sankalecha
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Nashik 422009, India
| | - Sachin Palnitkar
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Pune 411026, India
| | - Vikram Raut
- Department of Liver Transplant and HPB Surgery, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
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Tsoulfas G, Boletis I, Papalois V. Translational research and innovation in modern transplant practice: Paradigms from Greece and around the world. World J Transplant 2023; 13:25-27. [PMID: 36908305 PMCID: PMC9993189 DOI: 10.5500/wjt.v13.i2.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/14/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023] Open
Abstract
The continuous clinical and technological advances, together with the social, health and economic challenges that the global population faces, have created an environment where the evolution of the field of transplantation is essentially necessary. The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world. Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise, with a main focus on the field of translational research and innovation. The papers that are part of this Special Issue "Translational Research and Innovation and the current status of Transplantation in Greece" have presented innovative and meaningful approaches in modern transplant research and practice. They provide us with a clear overview of the current landscape in transplantation, including liver transplantation in the context of a major pandemic, the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation, while at the same time explore more recent challen ges, such as the issue of frailty in the transplant candidate and the changes brought by newer treatments, such as immunotherapy, in transplant oncology. Additionally, they offer us a glimpse of the effect that technological innovations, such as virtual reality, can have on transplantation, both in terms of clinical and educational aspects. Just as critical is the fact that this Special Issue emphasizes the multidisciplinary, collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering, advanced information technology and artificial intelligence. In this Special Issue, in addition to the clinical and research evolution of the field of transplantation, we are witnessing the importance of interdisciplinary collaboration in medicine.
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Affiliation(s)
- Georgios Tsoulfas
- Department of Transplantation Surgery, Aristotle University School of Medicine, Thessaloniki 54124, Greece
| | - Ioannis Boletis
- Department of Nephrology, EKPA University, Athens 11527, Greece
| | - Vassilios Papalois
- Department of Transplant Surgery, Imperial College Renal and Transplant Centre, London W12 0HS, United Kingdom
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