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Di Marco L, Romanzi A, Pivetti A, De Maria N, Ravaioli F, Salati M, Villa E, Di Benedetto F, Magistri P, Dominici M, Colecchia A, Di Sandro S, Spallanzani A. Suppressing, stimulating and/or inhibiting: The evolving management of HCC patient after liver transplantation. Crit Rev Oncol Hematol 2025; 207:104607. [PMID: 39725094 DOI: 10.1016/j.critrevonc.2024.104607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 12/20/2024] [Accepted: 12/22/2024] [Indexed: 12/28/2024] Open
Abstract
Liver transplantation (LT) is a curative strategy for hepatocellular carcinoma (HCC), but the risk of HCC recurrence remains a challenging problem. In patients with HCC recurrence after LT (HCC-R_LT), the locoregional and surgical approaches are complex, and the guidelines do not report evidence-based strategies for the management of immunosuppression. In recent years, immunotherapy has become an effective option for patients with advanced HCC in pre-transplant settings. However, due to the risk of potentially fatal allograft rejection, the use of immunotherapy is avoided in post-transplant settings. Combining immunosuppressants with immunotherapy in transplant patients is also challenging due to the complex tumor microenvironment and immunoreactivity. The fear of acute liver rejection and the lack of predictive factors hinder the successful clinical application of immunotherapy for post-liver transplantation HCC recurrence. This review aims to comprehensively summarize the risk of HCC-R_LT, the available evidence for the efficacy of immunotherapy in patients with HCC-R_LT, and the clinical issues regarding the innovative management of this patient population.
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Affiliation(s)
- Lorenza Di Marco
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy; Department of Biomedical, Metabolic and Neural Sciences, Clinical and Experimental Medicine Program, University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Adriana Romanzi
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Alessandra Pivetti
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Nicola De Maria
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna 40138, Italy.
| | - Massimiliano Salati
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Erica Villa
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy; National Institute of Gastroenterology IRCCS "Saverio de Bellis", Research Hospital, Castellana Grotte 70013, Italy.
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Massimo Dominici
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Antonio Colecchia
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Andrea Spallanzani
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy.
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Badwei N. Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope? World J Transplant 2024; 14:96637. [PMID: 39295978 PMCID: PMC11317853 DOI: 10.5500/wjt.v14.i3.96637] [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: 05/11/2024] [Revised: 06/08/2024] [Accepted: 06/24/2024] [Indexed: 07/31/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common liver malignancy and represents a serious cause of cancer-related mortality and morbidity. One of the favourable curative surgical therapeutic options for HCC is liver transplantation (LT) in selected patients fulfilling the known standard Milan/University of California San Francisco criteria which have shown better outcomes and longer-term survival. Despite careful adherence to the strict HCC selection criteria for LT in different transplant centres, the recurrence rate still occurs which could negatively affect HCC patients' survival. Hence HCC recurrence post-LT could predict patients' survival and prognosis, depending on the exact timing of recurrence after LT (early or late), and whether intra/extrahepatic HCC recurrence. Several factors may aid in such a complication, particularly tumour-related criteria including larger sizes, higher grades or poor tumour differentiation, microvascular invasion, and elevated serum alpha-fetoprotein. Therefore, managing such cases is challenging, different therapeutic options have been proposed, including curative surgical and ablative treatments that have shown better outcomes, compared to the palliative locoregional and systemic therapies, which may be helpful in those with unresectable tumour burden. To handle all these issues in our review.
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Affiliation(s)
- Nourhan Badwei
- Department of Tropical Medicine, Gastroenterology and Hepatology, Hepatoma Group, Ain Shams University, Cairo 11517, Egypt
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Cillo U, Carraro A, Avolio AW, Cescon M, Di Benedetto F, Giannelli V, Magistri P, Nicolini D, Vivarelli M, Lanari J. Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT). Updates Surg 2024; 76:725-741. [PMID: 38713396 DOI: 10.1007/s13304-024-01845-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 07/31/2023] [Indexed: 05/08/2024]
Abstract
Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.
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Affiliation(s)
- Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, General Surgery 2 Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Padua University Hospital, Via Giustiniani 2, 34128, Padua, PD, Italy.
| | - Amedeo Carraro
- Liver Transplant Unit, Department of Surgery and Oncology, University Hospital Trust of Verona, Verona, Italy
| | - Alfonso W Avolio
- Department of General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Matteo Cescon
- General Surgery and Transplantation Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria-Policlinico S.Orsola-Malpighi, Bologna, Italy
| | - Fabrizio Di Benedetto
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Valerio Giannelli
- Liver Unit, Department of Liver Transplant, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Paolo Magistri
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Daniele Nicolini
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Riuniti Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Riuniti Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Jacopo Lanari
- Department of Surgical, Oncological and Gastroenterological Sciences, General Surgery 2 Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Padua University Hospital, Via Giustiniani 2, 34128, Padua, PD, Italy
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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Cha DI, Kim JM, Jeong WK, Yi NJ, Choi GS, Rhu J, Lee KW, Sinn DH, Hwang JA, Lee WJ, Kim K, Suh KS, Joh JW. Recurrence-free Survival After Liver Transplantation Versus Surgical Resection for Hepatocellular Carcinoma: Role of High-risk MRI Features. Transplantation 2024; 108:215-224. [PMID: 37287096 DOI: 10.1097/tp.0000000000004675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
BACKGROUND This study aimed to evaluate recurrence-free survival (RFS) and overall survival (OS) after liver transplantation (LT) or liver resection (LR) for hepatocellular carcinoma (HCC) and perform subgroup analysis for HCC with high-risk imaging findings for recurrence on preoperative liver magnetic resonance imaging (MRI; high-risk MRI features). METHODS We included patients with HCC eligible for both LT and LR and received either of the treatments between June 2008 and February 2021 from 2 tertiary referral medical centers after propensity score-matching. RFS and OS were compared between LT and LR using Kaplan-Meier curves with the log-rank test. RESULTS Propensity score-matching yielded 79 patients in the LT group and 142 patients in the LR group. High-risk MRI features were noted in 39 patients (49.4%) in the LT group and 98 (69.0%) in the LR group. The Kaplan-Meier curves for RFS and OS were not significantly different between the 2 treatments among the high-risk group (RFS, P = 0.079; OS, P = 0.755). Multivariable analysis showed that treatment type was not a prognostic factor for RFS and OS ( P = 0.074 and 0.937, respectively). CONCLUSIONS The advantage of LT over LR for RFS may be less evident among patients with high-risk MRI features.
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Affiliation(s)
- Dong Ik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong Ah Hwang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Marrone G, Leone MS, Biolato M, Liguori A, Bianco G, Spoletini G, Gasbarrini A, Miele L, Pompili M. Therapeutic Approach to Post-Transplant Recurrence of Hepatocellular Carcinoma: Certainties and Open Issues. Cancers (Basel) 2023; 15:5593. [PMID: 38067299 PMCID: PMC10705300 DOI: 10.3390/cancers15235593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/03/2023] [Accepted: 11/18/2023] [Indexed: 01/12/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT). Careful candidate selection is a prerequisite to keep post-LT recurrence rates within acceptable percentages. In the pre-LT period, various types of locoregional treatments and/or systemic therapies can be used for bridging or downstaging purposes. In this context, one of the factors limiting the possibility of treatment is the degree of functional liver impairment. In the LT subject, no widely accepted indications are available to guide treatment of disease recurrence and heterogeneity exists between transplant centers. Improved liver function post LT makes multiple therapeutic strategies theoretically feasible, but patient management is complicated by the need to adjust immunosuppressive therapy and to assess potential toxicities and drug-drug interactions. Finally, there is controversy and uncertainty about the use of recently introduced immunotherapeutic drugs, mainly due to the risk of organ rejection. In this paper, we will review the most recent available literature on the management of post-transplant HCC recurrence, discussing evidence and controversies.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Maurizio Pompili
- Medical and Surgical Sciences Department, Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Durkin C, Schaubel DE, Xu Y, Mahmud N, Kaplan DE, Abt PL, Bittermann T. Induction Immunosuppression Does Not Worsen Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma. Transplantation 2023; 107:1524-1534. [PMID: 36695564 PMCID: PMC11972139 DOI: 10.1097/tp.0000000000004487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated. RESULTS Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [ P < 0.001]; HR 0.64 in the explant model [ P = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P = 0.019; versus no induction plus 3-drug therapy). CONCLUSIONS In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI.
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Affiliation(s)
- Claire Durkin
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Douglas E. Schaubel
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Yuwen Xu
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
- Section of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Section of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Peter L. Abt
- Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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Mamone G, Caruso S, Milazzo M, Porrello G, Di Piazza A, Gentile G, Carollo V, Crinò F, Marrone G, Sparacia G, Maruzzelli L, Miraglia R, Gruttadauria S. Imaging of hepatocellular carcinoma recurrence after liver transplantation. Insights Imaging 2023; 14:84. [PMID: 37184688 DOI: 10.1186/s13244-023-01425-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/05/2023] [Indexed: 05/16/2023] Open
Abstract
Liver transplantation (LT) provides the highest survival benefit to patients with unresectable hepatocellular carcinoma (HCC). The Milan criteria have been developed for the selection of LT candidates with the goal of improving survival and maintaining an acceptable risk of HCC recurrence. Despite this, recurrence of HCC after LT occurs in up to 20% of cases and represents a major concern due to the poor prognosis of these patients. Furthermore, several extended criteria for the selection of LT candidates have been proposed to account for the growing demand for organs and the resultant increase in the risk of HCC recurrence. Radiologists should be aware that HCC can recur after LT with multiple organ involvement. Knowledge of the location and radiologic appearance of recurrent HCC is necessary to ensure the choice of the most appropriate therapy. This paper aims to comprehensively summarize the spectrum of HCC recurrence after LT and to examine and discuss the imaging features of these lesions. CRITICAL RELEVANCE STATEMENT: This paper aims to share a review of imaging findings of HCC recurrence after LT and to make radiologists familiar with the spectrum of this disease.
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Affiliation(s)
- Giuseppe Mamone
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy.
| | - Settimo Caruso
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Mariapina Milazzo
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Giorgia Porrello
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Ambra Di Piazza
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Giovanni Gentile
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Vincenzo Carollo
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Francesca Crinò
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Gianluca Marrone
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Gianvincenzo Sparacia
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Luigi Maruzzelli
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Roberto Miraglia
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127, Palermo, Italy
| | - Salvatore Gruttadauria
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
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9
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Posttransplant Hepatocellular Carcinoma Surveillance: A Cost-effectiveness and Cost-utility Analysis. Ann Surg 2023; 277:e359-e365. [PMID: 34928553 DOI: 10.1097/sla.0000000000005295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Assess cost-effectiveness and -utility associated with posttransplant HCC surveillance compared to standard follow-up. SUMMARY OF BACKGROUND DATA Despite lack of prospective clinical data, expert consensus recommends posttransplant surveillance to detect HCC recurrence in a latent phase, while it might be amenable to curative-intent therapy. METHODS A Markov-based transition model was created to estimate life expectancy and quality-of-life among liver transplant patients undergoing HCC surveillance. Models were built for 2 cohorts: 1 undergoing HCC surveillance with contrast-enhanced computed tomography of chest and abdomen and serum alpha-fetoprotein analysis and the other receiving standard posttransplant follow-up. Primary model outputs included LY and QALY gains, incremental cost-effectiveness ratio, and incremental cost-utility ratio. Willingness-to-pay for a QALY gain (cost-effectiveness threshold) was used to estimate efficiency. RESULTS Surveillance was marginally more effective versus no surveillance, resulting in means of 0.069 LYs and 0.026 QALYs gained. Costs for surveillance were increased by an average of 988.32€, resulting in incremental cost-effectiveness ratio 14,410.15€/LY and incremental cost-utility ratio 37,547.97€/QALY. Surveillance did not seem cost-effective in our setting, considering willingness-to-pay threshold of 25,000€/QALY. Probabilistic sensitivity analysis indicated surveillance might be cost-effective in 42% of cases, but degree of uncertainty in the analysis was high. CONCLUSIONS Performing posttransplant HCC surveillance offers marginal clinical benefits and increases costs. Although expert consensus supports surveillance, results of this decision analysis raise doubt regarding the utility of such recommendations and support ongoing need for prospective clinical trials.
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10
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Novruzbekov MS, Lutsyk KN, Olisov OD, Magomedov KM, Kazymov BI, Alekberov KF, Akhmedov AR, Yaremin BI. [Indocyanine green in liver transplantation]. Khirurgiia (Mosk) 2023:63-72. [PMID: 37682549 DOI: 10.17116/hirurgia202309263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/09/2023]
Abstract
The purpose of this study was to evaluate the first own experience of using indocyanine green (ICG) in liver transplantation compared to literature data and to determine its potential for clinical practice. Liver transplantation is an effective option for patients with end-stage disease, but this procedure is associated with many problems such as graft rejection, graft dysfunction, surgical risk and postoperative management. Modern methods for assessing graft function have their limitations, so a more efficient method is needed. According to this review, ICG fluorescence is valuable for effective intraoperative blood flow control, assessment of graft function, intraoperative and postoperative monitoring of clinical status. ICG fluorescence can also predict clinical status of patients at all stages of liver transplantation. Routine ICG fluorescence method is advisable in liver transplantation to improve outcomes and optimize treatment process.
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Affiliation(s)
- M S Novruzbekov
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - K N Lutsyk
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
| | - O D Olisov
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - K M Magomedov
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
| | - B I Kazymov
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
| | - K F Alekberov
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
| | - A R Akhmedov
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
| | - B I Yaremin
- Sklifosovsky Research Institute for Emergency Care, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
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11
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Nishio T, Ito T, Hata K, Taura K, Hatano E. Current status of liver transplantation for non-B non-C liver cirrhosis and hepatocellular carcinoma. Ann Gastroenterol Surg 2023; 7:42-52. [PMID: 36643372 PMCID: PMC9831911 DOI: 10.1002/ags3.12612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 08/05/2022] [Indexed: 01/18/2023] Open
Abstract
Recently, non-B non-C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5-5-500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non-B non-C cirrhosis and HCC, are highlighting the importance of peri-transplant management of patients with various comorbidities. The post-LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome-related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome-related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post-LT outcomes. Patient management in the peri-transplant period as well as risk assessment for LT are key to improving post-LT outcomes in the era of a growing number of cases of LT for non-B non-C liver diseases.
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Affiliation(s)
- Takahiro Nishio
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takashi Ito
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Koichiro Hata
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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12
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Sposito C, Citterio D, Virdis M, Battiston C, Droz Dit Busset M, Flores M, Mazzaferro V. Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma. World J Gastroenterol 2022; 28:4929-4942. [PMID: 36160651 PMCID: PMC9494935 DOI: 10.3748/wjg.v28.i34.4929] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/05/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Matteo Virdis
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Carlo Battiston
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
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13
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Suzuki R, Goto R, Kawamura N, Watanabe M, Ganchiku Y, Hatanaka KC, Hatanaka Y, Kamiyama T, Shimamura T, Taketomi A. Efficient multiple treatments including molecular targeting agents in a case of recurrent hepatocellular carcinoma, post-living donor liver transplantation. Clin J Gastroenterol 2022; 15:755-764. [DOI: 10.1007/s12328-022-01643-3] [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: 09/14/2021] [Accepted: 05/01/2022] [Indexed: 11/28/2022]
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14
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Ahmed O, Vachharajani N, Croome KP, Tabrizian P, Agopian V, Halazun K, Hong JC, Dageforde LA, Chapman WC, Doyle MM. Are Current National Review Board Downstaging Protocols for Hepatocellular Carcinoma Too Restrictive? J Am Coll Surg 2022; 234:579-588. [PMID: 35290278 DOI: 10.1097/xcs.0000000000000140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Liver transplantation (LT) is an effective strategy for patients with unresectable hepatocellular carcinoma (HCC). To qualify for standardized LT model for end-stage liver disease exception points, the United Network for Organ Sharing National Liver Review Board (NLRB) requires that the presenting and final HCC tumor burden be within the University of California San Francisco criteria, which were recently expanded (within expanded UCSF [W-eUCSF]). Current NLRB criteria may be too restrictive because it has been shown previously that the initial burden does not predict LT failure when tumors downstage to UCSF. This study aims to assess LT outcomes for HCC initially presenting beyond expanded UCSF (B-eUCSF) criteria in a large multicenter collaboration. STUDY DESIGN Comparisons of B-eUCSF and W-eUCSF candidates undergoing LT at seven academic institutions between 2001 and 2017 were made from a multi-institutional database. Survival outcomes were compared by Kaplan-Meier and Cox regression analyses. RESULTS Of 1,846 LT recipients with HCC, 86 (5%) met B-eUCSF criteria at initial presentation, with the remainder meeting W-eUCSF criteria. Despite differences in tumor burden, B-eUCSF candidates achieved comparable 1-, 5- and 10-year overall (89%, 70%, and 55% vs 91%, 74%, and 60%, respectively; p = 0.2) and disease-free (82%, 60%, and 53% vs 89%, 71%, and 59%, respectively; p = 0.07) survival to patients meeting W-eUCSF criteria after LT. Despite increased tumor recurrence in B-eUCSF vs W-eUCSF patients (24% vs 10%, p = 0.0002), post-recurrence survival was similar in both groups (p = 0.69). CONCLUSION Transplantation for patients initially presenting with HCC B-eUSCF criteria offers a survival advantage similar to those with tumors meeting W-eUCSF criteria at presentation. The current NLRB policy is too stringent, and considerations to expand criteria should be discussed.
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Affiliation(s)
- Ola Ahmed
- From the Division of Abdominal Organ Transplantation, Department of Surgery, Washington University School of Medicine, Saint Louis, MO (Ahmed, Vachharajani, Chapman, Doyle)
| | - Neeta Vachharajani
- From the Division of Abdominal Organ Transplantation, Department of Surgery, Washington University School of Medicine, Saint Louis, MO (Ahmed, Vachharajani, Chapman, Doyle)
| | - Kris P Croome
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL (Croome)
| | - Parissa Tabrizian
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Tabrizian)
| | - Vatche Agopian
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA (Agopian)
| | - Karim Halazun
- New York-Presbyterian Hospital, Weill Cornell, New York, NY (Halazun)
| | - Johnny C Hong
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI (Hong)
| | - Leigh Anne Dageforde
- Department of Surgery, Division of Transplantation, Massachusetts General Hospital, Boston, MA (Dageforde)
| | - William C Chapman
- From the Division of Abdominal Organ Transplantation, Department of Surgery, Washington University School of Medicine, Saint Louis, MO (Ahmed, Vachharajani, Chapman, Doyle)
| | - Mb Majella Doyle
- From the Division of Abdominal Organ Transplantation, Department of Surgery, Washington University School of Medicine, Saint Louis, MO (Ahmed, Vachharajani, Chapman, Doyle)
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15
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Agarwal PD, Lucey MR. Management of hepatocellular carcinoma recurrence after liver transplantation. Ann Hepatol 2022; 27:100654. [PMID: 34929349 DOI: 10.1016/j.aohep.2021.100654] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/30/2021] [Accepted: 11/30/2021] [Indexed: 02/04/2023]
Abstract
Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy.
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Affiliation(s)
- Parul D Agarwal
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, Suite 4224, Madison, WI 53705, United States.
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, Suite 4224, Madison, WI 53705, United States
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16
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Murphy S, Hodgkinson P, O'Rourke TR, Slater K, Yeung S, Fawcett J. Long term outcomes of hepatic resection following orthotopic liver transplant. ANZ J Surg 2021; 92:526-530. [PMID: 34927324 DOI: 10.1111/ans.17416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 11/12/2021] [Accepted: 11/17/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Liver resection is sometimes used as a graft saving procedure following orthotopic liver transplantation. METHODS In this single centre retrospective cohort study, 12 adult patients underwent resection over a 20 year period, including recipients of split livers and second grafts. RESULTS Indications for resection were vascular (portal vein obstruction and hepatic artery thrombus), biliary (ischaemic cholangiopathy, chronic biliary obstruction, biliary-vascular fistula and biloma) and recurrence of disease (primary sclerosing cholangitis [PSC] and hepatocellular carcinoma [HCC]). There was no perioperative mortality. Median follow up was 89 months. At the completion of the study 40% of patients had functioning grafts. One third required retransplantation with a median 1 year 6 months post resection. Three patients were deceased (recurrent HCC n = 1, PSC n = 1 and unspecified causes n = 1). Total graft survival was 91.7% at 1 year, 73.3% at 5 years and 64.2% at 10 years. CONCLUSIONS Liver resection following liver transplant in select patients may salvage the graft or delay the need for retransplantation.
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Affiliation(s)
- Skyle Murphy
- Transplant Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Griffith Health Centre, Griffith University Medical School, Gold Coast Campus, Gold Coast, Queensland, Australia
| | - Peter Hodgkinson
- Transplant Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Thomas R O'Rourke
- Transplant Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Kellee Slater
- Transplant Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Shinn Yeung
- Transplant Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Jonathan Fawcett
- Transplant Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia
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17
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Hsu PJ, Hung HC, Lee JC, Wang YC, Cheng CH, Wu TH, Wu TJ, Chou HS, Chan KM, Lee WC, Lee CF. Human Cytomegalovirus Is Associated with Lower HCC Recurrence in Liver Transplant Patients. Curr Oncol 2021; 28:4281-4290. [PMID: 34898547 PMCID: PMC8544456 DOI: 10.3390/curroncol28060364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/16/2021] [Accepted: 10/19/2021] [Indexed: 11/24/2022] Open
Abstract
Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia (p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20-0.97), microscopic vascular invasion (p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78-8.36), and tumor status beyond the Milan criteria (p = 0.001; OR = 3.69; 95% CI = 1.77-7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.
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Affiliation(s)
- Po-Jung Hsu
- Department of General Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan;
| | - Hao-Chien Hung
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Jin-Chiao Lee
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Yu-Chao Wang
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Chih-Hsien Cheng
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Tsung-Han Wu
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Ting-Jung Wu
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Hong-Shiue Chou
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Kun-Ming Chan
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Wei-Chen Lee
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
| | - Chen-Fang Lee
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou 333, Taiwan; (H.-C.H.); (J.-C.L.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (T.-J.W.); (H.-S.C.); (K.-M.C.); (W.-C.L.)
- College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan
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18
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L R, T I, Mpaw C, H M, G S. THE MANAGEMENT OF POST-TRANSPLANTATION RECURRENCE OF HEPATOCELLULAR CARCINOMA. Clin Mol Hepatol 2021; 28:1-16. [PMID: 34610652 PMCID: PMC8755475 DOI: 10.3350/cmh.2021.0217] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/03/2021] [Indexed: 11/15/2022] Open
Abstract
The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.
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Affiliation(s)
- Rajendran L
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Ivanics T
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.,Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Claasen Mpaw
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands
| | - Muaddi H
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Sapisochin G
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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19
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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20
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Zucker KM, Gomez PA, Kezirian O, Mehta S. Pre-Transplant Factors Influencing Rates of Hepatocellular Carcinoma Recurrence in Liver Transplant Recipients. Gastroenterology Res 2021; 14:190-193. [PMID: 34267835 PMCID: PMC8256902 DOI: 10.14740/gr1402] [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: 04/26/2021] [Accepted: 06/11/2021] [Indexed: 12/03/2022] Open
Abstract
Background The aim of the study was to determine factors influencing hepatocellular carcinoma (HCC) recurrence in a cohort of patients who underwent liver transplantation (LT) at a large, tertiary-care medical center. Methods A total of 132 patients with the diagnosis of HCC at time of transplant were evaluated for HCC recurrence over a 7-year period. Nine patients were found to have HCC recur post-LT. Results No significant demographic values were found to indicate recurrence. Pre-LT factors potentially influencing HCC recurrence rates included number of days between HCC diagnosis and date of LT (P = 0.015), caudate lobe involvement (P = 0.019), increased use of radiation therapies pre-LT (P = 0.011), and total number of locoregional therapies (LRT) pre-LT (P < 0.001). Post-transplant outcomes demonstrated a significant difference in deep venous thrombosis (DVT) in the recurrent vs. non-recurrent groups (P = 0.035). Conclusions The prevalence of HCC recurrence in this study was lower than the national average, yet difficulty still exists in predicting pre-LT factors which may influence HCC recurrence rates.
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Affiliation(s)
- Kelly M Zucker
- Department of Gastroenterology, University of Arizona College of Medicine Phoenix, Banner University Medical Center-Phoenix, Phoenix, AZ, USA
| | - Paul A Gomez
- Department of Internal Medicine, University of Arizona College of Medicine Phoenix, Banner University Medical Center-Phoenix, Phoenix, AZ, USA
| | - Olivia Kezirian
- Department of Data Management, University of Arizona College of Medicine Phoenix, Banner University Medical Center-Phoenix, Phoenix, AZ, USA
| | - Shivang Mehta
- Transplant and Advanced Liver Disease Center, University of Arizona College of Medicine Phoenix, Banner University Medical Center-Phoenix, Phoenix, AZ, USA
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21
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Nitta H, Younès A, El-Domiaty N, Karam V, Sobesky R, Vibert E, Coilly A, Maria Antonini T, De Martin E, Cherqui D, Baba H, Rosmorduc O, Adam R, Samuel D, Saliba F. High trough levels of everolimus combined to sorafenib improve patients survival after hepatocellular carcinoma recurrence in liver transplant recipients. Transpl Int 2021; 34:1293-1305. [PMID: 33932239 DOI: 10.1111/tri.13897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 03/19/2021] [Accepted: 04/21/2021] [Indexed: 12/21/2022]
Abstract
Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) occurs in 10%-20% of patients transplanted for HCC. The treatment of HCC recurrence after LT remains a challenge. Consecutive patients who underwent LT for HCC between 2005 and 2015 at our center were recruited. Characteristics of patients with recurrence, modalities of treatment and outcome were collected retrospectively. Patient survival was analyzed according to HCC recurrence therapeutic strategy. Among 306 transplanted patients, 43 patients (14.1%) developed recurrence with a median survival time after recurrence of 10.9 months (95%CI: 6.6-18.6). Survival of patients treated with Sorafenib (SOR) and everolimus (EVL) (n = 19) was significantly better than that of the group treated with other strategies (n = 24) (P = 0.001). Multivariable analysis demonstrated that SOR plus EVL therapy and absence of dissemination at diagnosis of recurrence were independent predictive factors of prolonged survival after recurrence. Among the patients who treated with EVL, survival of patients with controlled EVL blood trough levels ≥5 ng/ml was significantly better compared to those with EVL trough levels <5 ng/ml (P = 0.021). Combination therapy of sorafenib and everolimus was an independent predictor for better survival after HCC recurrence. Patients with controlled everolimus trough level ≥5 ng/ml might get the best survival benefit.
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Affiliation(s)
- Hidetoshi Nitta
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Aline Younès
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Nada El-Domiaty
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France.,Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Vincent Karam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Rodolphe Sobesky
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Eric Vibert
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Teresa Maria Antonini
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Eleonora De Martin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Daniel Cherqui
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Olivier Rosmorduc
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
| | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France
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Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC. AREAS COVERED In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC. EXPERT OPINION The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.
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Affiliation(s)
- Daniel Hoffman
- Department of Surgery, University of California , San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California , San Francisco, CA, USA
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23
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A National Survey of Hepatocellular Carcinoma Surveillance Practices Following Liver Transplantation. Transplant Direct 2020; 7:e638. [PMID: 33324743 PMCID: PMC7725259 DOI: 10.1097/txd.0000000000001086] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/24/2020] [Accepted: 09/25/2020] [Indexed: 12/13/2022] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT. Methods We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries. Results Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific "cutoff" values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol. Conclusions Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.
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Outcomes of Liver Resections after Liver Transplantation at a High-Volume Hepatobiliary Center. J Clin Med 2020; 9:jcm9113685. [PMID: 33212913 PMCID: PMC7698397 DOI: 10.3390/jcm9113685] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/05/2020] [Accepted: 11/15/2020] [Indexed: 12/12/2022] Open
Abstract
Although more than one million liver transplantations have been carried out worldwide, the literature on liver resections in transplanted livers is scarce. We herein report a total number of fourteen patients, who underwent liver resection after liver transplantation (LT) between September 2004 and 2017. Hepatocellular carcinomas and biliary tree pathologies were the predominant indications for liver resection (n = 5 each); other indications were abscesses (n = 2), post-transplant lymphoproliferative disease (n = 1) and one benign tumor. Liver resection was performed at a median of 120 months (interquartile range (IQR): 56.5-199.25) after LT with a preoperative Model for End-Stage Liver Disease (MELD) score of 11 (IQR: 6.75-21). Severe complications greater than Clavien-Dindo Grade III occurred in 5 out of 14 patients (36%). We compared liver resection patients, who had a treatment option of retransplantation (ReLT), with actual ReLTs (excluding early graft failure or rejection, n = 44). Bearing in mind that late ReLT was carried out at a median of 117 months after first transplantation and a median of MELD of 32 (IQR: 17.5-37); three-year survival following liver resection after LT was similar to late ReLT (50.0% vs. 59.1%; p = 0.733). Compared to ReLT, liver resection after LT is a rare surgical procedure with significantly shorter hospital (mean 25, IQR: 8.75-49; p = 0.034) and ICU stays (mean 2, IQR: 1-8; p < 0.001), acceptable complications and survival rates.
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25
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Yang Z, Wang S, Tian XY, Xie QF, Zhuang L, Li QY, Chen CZ, Zheng SS. Impact of treatment modalities on patients with recurrent hepatocellular carcinoma after liver transplantation: Preliminary experience. Hepatobiliary Pancreat Dis Int 2020; 19:365-370. [PMID: 32553774 DOI: 10.1016/j.hbpd.2020.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 06/01/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Post-liver transplantation (LT) hepatocellular carcinoma (HCC) recurrence still occurs in approximately 20% of patients and drastically affects their survival. This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population. METHODS A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study. Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival. RESULTS Of the 64 patients with recurrent HCC after LT, those who received radical resection followed by nonsurgical therapy had a median overall survival (OS) of 20.9 months after HCC recurrence, significantly superior to patients who received only nonsurgical therapy (9.4 months) or best supportive care (2.4 months). The one- and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy (93.8%, 52.6%), poor for patients receiving only nonsurgical therapy (30.8%, 10.8%), and dismal for patients receiving best supportive care (0%, 0%; overall P < 0.001). Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months, far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure (12 months, P < 0.001). Compared with tacrolimus-based immunosuppressive therapy, OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence (P = 0.035). Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival. CONCLUSIONS Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence. A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.
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Affiliation(s)
- Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China
| | - Shuo Wang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China
| | - Xin-Yao Tian
- Division of Hepatobiliary Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, China
| | - Qin-Fen Xie
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China
| | - Li Zhuang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China
| | - Qi-Yong Li
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China
| | - Cheng-Ze Chen
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, 848 Dongxin Road, Hangzhou 310022, China; Division of Hepatobiliary Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, China; National Clinical Research Center of Infectious Diseases, 79 Qingchun Road, Hangzhou 310003, China.
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26
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Ekpanyapong S, Philips N, Loza BL, Abt P, Furth EE, Tondon R, Khungar V, Olthoff K, Shaked A, Hoteit MA, Reddy KR. Predictors, Presentation, and Treatment Outcomes of Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Large Single Center Experience. J Clin Exp Hepatol 2020; 10:304-315. [PMID: 32655233 PMCID: PMC7335705 DOI: 10.1016/j.jceh.2019.11.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT. METHODS Patients with recurrent HCC after LT between January 1996 and December 2017 were retrospectively reviewed. RESULTS Of 711 patients, 96 (13.5%) patients had post-LT HCC recurrence. The median time to recurrence was 17.1 months, and the median survival was 10.1 months. Initial recurrence was more often in the graft (34.4%), and most (60.4%) had multiple recurrent lesions, and 26% were in multiple sites. In multivariate analysis, factors associated with shorter survival were poorly differentiated histology in explant (Hazard ratio [HR] = 1.96; p = 0.027), bilirubin ≥1.2 mg/dL (HR = 2.47; p = 0.025), and albumin <3.5 mg/dL (HR = 2.13; p = 0.014) at recurrence, alpha-fetoprotein at recurrence ≥ 1000 ng/mL (HR = 2.96; p = 0.005), and peritoneal disease (HR = 3.20; p = 0.022). There was an increased survival in patients exposed to sirolimus (HR = 0.32; p < 0.0001). CONCLUSIONS Recurrent HCC after LT is often in extrahepatic sites with a decreased survival in those with poorly differentiated explant pathology, high bilirubin, low albumin, marked elevation of alpha-fetoprotein at recurrence, and peritoneal recurrence. Sirolimus-based immunosuppression may provide benefit.
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Key Words
- AFP, alpha-fetoprotein
- ALP, alkaline phosphatase
- ALT, alanine transaminase
- CNI, calcineurin inhibitor
- CT, computed tomography
- HBV, hepatitis B virus
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- INR, international normalized ratio
- LT, Liver transplantation
- MRI, magnetic resonance imaging
- NASH, nonalcoholic steatohepatitis
- RETREAT, Risk Estimation of Tumor Recurrence After Transplant
- RFA, radiofrequency ablation
- TACE, transarterial chemoembolization
- UCSF, University of California San Francisco
- UNOS, United Network for Organ Sharing
- hepatocellular carcinoma
- immunosuppression
- liver transplantation
- mTOR, mammalian target of rapamycin
- recurrence
- survival
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Neil Philips
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Bao-Li Loza
- Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Peter Abt
- Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Emma E. Furth
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Rashmi Tondon
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Vandana Khungar
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Kim Olthoff
- Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Abraham Shaked
- Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Maarouf A. Hoteit
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - K. Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
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Tohyama T, Sakamoto K, Tamura K, Nakamura T, Watanabe J, Wakisaka H, Takada Y. Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: a case report and literature review. World J Surg Oncol 2020; 18:109. [PMID: 32466780 PMCID: PMC7257203 DOI: 10.1186/s12957-020-01873-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/06/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection. CASE PRESENTATION A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph node metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib. CONCLUSION It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.
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Affiliation(s)
- Taiji Tohyama
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
- Department of Surgery, Kurashiki Medical Center, Bakuro-cho, Kurashiki, Okayama, 710-8522, Japan.
| | - Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Kei Tamura
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Taro Nakamura
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Jota Watanabe
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Hiroyuki Wakisaka
- Laboratory of Head and Neck Surgery, Ehime Prefectural University of Health Sciences, 543, Takoda, Tobe-cho, Iyo-gun, Ehime, 791-2101, Japan
| | - Yasutsugu Takada
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
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28
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Experience With Early Sorafenib Treatment With mTOR Inhibitors in Hepatocellular Carcinoma Recurring After Liver Transplantation. Transplantation 2020; 104:568-574. [DOI: 10.1097/tp.0000000000002955] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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29
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Verna EC, Patel YA, Aggarwal A, Desai AP, Frenette C, Pillai AA, Salgia R, Seetharam A, Sharma P, Sherman C, Tsoulfas G, Yao FY. Liver transplantation for hepatocellular carcinoma: Management after the transplant. Am J Transplant 2020; 20:333-347. [PMID: 31710773 DOI: 10.1111/ajt.15697] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
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Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University, New York, New York, USA
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Avin Aggarwal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tuscon, Arizona, USA
| | - Archita P Desai
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Catherine Frenette
- Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Anjana A Pillai
- Center for Liver Diseases, University of Chicago Medicine, Chicago, Illinois, USA
| | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anil Seetharam
- Transplant Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Pratima Sharma
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Courtney Sherman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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30
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Hong SK, Lee K, Yoon KC, Kim H, Ahn S, Kim H, Lee J, Cho J, Yi N, Suh K. Different prognostic factors and strategies for early and late recurrence after adult living donor liver transplantation for hepatocellular carcinoma. Clin Transplant 2019; 33:e13703. [DOI: 10.1111/ctr.13703] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 08/23/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Suk Kyun Hong
- Department of Surgery Seoul National University College of Medicine Seoul Korea
| | - Kwang‐Woong Lee
- Department of Surgery Seoul National University College of Medicine Seoul Korea
| | - Kyung Chul Yoon
- Department of Surgery Division of HBP Surgery & Liver Transplantation Anam Hospital Korea University College of Medicine Seoul Korea
| | - Hyo‐Sin Kim
- Department of Surgery Chonnam National University Medical School and Hospital Gwangju Korea
| | - Sung‐Woo Ahn
- Department of Surgery Chonbuk National University College of Medicine Jeonju Korea
| | - Hyeyoung Kim
- Department of Surgery Eulji University Hospital Eulji University College of Medicine Daejeon Korea
| | - Jeong‐Moo Lee
- Department of Surgery Seoul National University College of Medicine Seoul Korea
| | - Jae‐Hyung Cho
- Department of Surgery Seoul National University College of Medicine Seoul Korea
| | - Nam‐Joon Yi
- Department of Surgery Seoul National University College of Medicine Seoul Korea
| | - Kyung‐Suk Suh
- Department of Surgery Seoul National University College of Medicine Seoul Korea
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31
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Santopaolo F, Lenci I, Milana M, Manzia TM, Baiocchi L. Liver transplantation for hepatocellular carcinoma: Where do we stand? World J Gastroenterol 2019; 25:2591-2602. [PMID: 31210712 PMCID: PMC6558441 DOI: 10.3748/wjg.v25.i21.2591] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/09/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.
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Affiliation(s)
- Francesco Santopaolo
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Ilaria Lenci
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Tommaso Maria Manzia
- Transplant Surgery Unit, Department of Surgery, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
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Abstract
Liver transplantation is the definitive treatment for patients with end-stage liver disease. Liver transplantation is also the optimal treatment for patients with hepatocellular carcinoma (HCC), especially in the setting of chronic liver disease. Unfortunately, due to the worldwide shortage of organs, this treatment is not available for all patients with HCC. Strict selection criteria have been developed in order to obtain optimal results. A surgical perspective of the preoperative selection, perioperative management, and postoperative care of patients is reviewed in depth and provides an overview for obtaining optimal long-term results from liver transplantation for HCC. With rigorous selection and patient management, excellent long-term outcomes can be obtained with liver transplantation for patients with HCC.
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33
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Au KP, Chok KSH. Multidisciplinary approach for post-liver transplant recurrence of hepatocellular carcinoma: A proposed management algorithm. World J Gastroenterol 2018; 24:5081-5094. [PMID: 30568386 PMCID: PMC6288653 DOI: 10.3748/wjg.v24.i45.5081] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 10/21/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023] Open
Abstract
A large number of liver transplants have been performed for hepatocellular carcinoma (HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy (SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligo-recurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a pre-requisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences.
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Affiliation(s)
- Kin Pan Au
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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Saberi B, Garonzik-Wang J, Ma M, Ajayi T, Kim A, Luu H, Jakhete N, Pustavoitau A, Anders RA, Georgiades C, Kamel I, Ottmann S, Philosophe B, Cameron AM, Gurakar A. Accuracy of Milan, University of California San Francisco, and Up-To-7 Criteria in Predicting Tumor Recurrence Following Deceased-Donor Liver Transplant in Patients With Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2018; 18:463-469. [PMID: 30084757 DOI: 10.6002/ect.2017.0288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES We aimed to investigate the accuracy of the Milan, University of California San Francisco, and Up-to-7 criteria in predicting tumor recurrence after liver transplant for hepatocellular carcinoma. MATERIALS AND METHODS For this study, 165 patients with deceased-donor liver transplant for hepatocellular carcinoma were evaluated. The Milan, University of California San Francisco, and Up-to-7 criteria were calculated based on explant pathology. RESULTS Tumor recurrence rate after liver transplant was 14.6%. Of 165 patients, 115 (70%) were within Milan, 131 (79%) were within University of California San Francisco, and 135 (82%) were within Up-to-7 criteria. The odds ratio of tumor recurrence in patients outside versus within criteria for Milan, University of California San Francisco, and Up-to-7 was 3.6 (95% confidence interval, 1.5-9.1; P = .005), 7.5 (95% confidence interval, 2.5-19.3; P < .001), and 7.5 (95% confidence interval, 2.9-19.6; P < .001) times higher, respectively. The sensitivity of being outside of Milan in predicting tumor recurrence was comparable to University of California San Francisco and Up-to-7 criteria (56.5%, 56.5%, and 52.2%, respectively). Specificity was highest in Up-to-7 (87.3%) versus 85.2% for University of California San Francisco and 73.9% for Milan criteria. The area under the curve for Milan, University of California San Francisco, and Up-to-7 criteria was 0.63, 0.65, and 0.63. CONCLUSIONS Application of standard criteria has significantly improved prediction of hepatocellular carcinoma recurrence. However, these criteria are inadequate, supporting the importance of other factors, including tumor biology. Research is ongoing in discovering novel biomarkers as predictors of tumor recurrence.
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Affiliation(s)
- Behnam Saberi
- From the Division of Gastroenterology and Hepatology-Transplant Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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35
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Bauschke A, Altendorf-Hofmann A, Kissler H, Koch A, Malessa C, Settmacher U. Validity of eleven prognostic scores with respect to intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation. J Cancer Res Clin Oncol 2017; 143:2595-2605. [PMID: 28849266 DOI: 10.1007/s00432-017-2507-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 08/17/2017] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Tumor recurrence is the most frequent cause of death after liver transplantation for hepatocellular carcinoma. We selected ten other prognostic classifications to evaluate their potential to predict the risk of recurrence after LT for HCC as compared to the Milan classification. All of the other scores have not been compared with one another in a single cohort. METHODS Data of 147 consecutive patients transplanted at our department between 1996 and 2014 were analyzed and staged for morphological and functional scores of underlying liver disease. For long-term follow-up, we analyzed intrahepatic (within the liver ± distant metastases) and extrahepatic (distant metastases only) recurrence separately. RESULTS AND CONCLUSIONS The median survival time for all patients was 106 months. The 5- and 10-year observed survival rates were 61 and 43%, respectively. The observed cumulative 5- and 10-year recurrence rates were 37 and 39%, respectively, 10-year intrahepatic and extrahepatic recurrence rates were 12 and 27%, respectively. Median survival time after diagnosis of first recurrence was 7.5 (0-120) months; 2 and 18 months for all, intra- and extrahepatic recurrence, respectively. UCSF-, up to seven-, Shanghai Fudan- or Duvoux classifications can identify patients with a cumulative 10-year recurrence rate below 20%. The pre-therapeutic AFP level should be considered in addition to the geometry of the intrahepatic lesions.
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Affiliation(s)
- A Bauschke
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany.
| | - A Altendorf-Hofmann
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany
| | - H Kissler
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany
| | - A Koch
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany
| | - C Malessa
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany
| | - U Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany
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Mancuso A, Maringhini A. Management of hepatocellular carcinoma recurrence after liver transplant is far from perfect. Am J Surg 2017; 216:389-390. [PMID: 28454660 DOI: 10.1016/j.amjsurg.2017.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 04/05/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Andrea Mancuso
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico - Di Cristina - Benfratelli, Piazzale Leotta 4, 90100, Palermo, Italy.
| | - Alberto Maringhini
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico - Di Cristina - Benfratelli, Piazzale Leotta 4, 90100, Palermo, Italy
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37
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Martin RC, Bruenderman E, Cohn A, Piperdi B, Miksad R, Geschwind JF, Goldenberg A, Sanyal A, Zigmont E, Babajanyan S, Foreman P, Mantry P, McGuire B, Gholam P. Sorafenib use for recurrent hepatocellular cancer after resection or transplantation: Observations from a US regional analysis of the GIDEON registry. Am J Surg 2017; 213:688-695. [DOI: 10.1016/j.amjsurg.2016.10.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 10/18/2016] [Accepted: 10/24/2016] [Indexed: 12/26/2022]
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38
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Fernandez-Sevilla E, Allard MA, Selten J, Golse N, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Adam R. Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection? Liver Transpl 2017; 23:440-447. [PMID: 28187493 DOI: 10.1002/lt.24742] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 01/12/2017] [Accepted: 01/26/2017] [Indexed: 02/06/2023]
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is widely considered as a terminal condition. Therefore, the role of surgery is uncertain in this case. The purpose of this study was to identify the prognostic factors of survival after post-LT HCC recurrence and to evaluate the impact of surgery in this setting. All patients transplanted for HCC between 1991 and 2013 in a single institution and who further developed a post-LT recurrence were included in this study. Univariate and multivariate analyses were performed to identify factors affecting postrecurrence survival. Of the 493 patients transplanted for HCC, a total of 70 (14.2%) consecutive patients developed a recurrence after a median disease-free interval of 17 months. Median survival (MS) from the time of recurrence was 19 months, with a 3-year postrecurrence survival of 26%. Most recurrences were extrahepatic (lung, lymph node, and bone; n = 51; 72.9%), whereas only intrahepatic recurrences were observed in 2 (2.8%) patients. Both intrahepatic and extrahepatic locations were found in 17 (24.3%) patients. A total of 22 (31.4%) patients underwent macroscopically complete resection of the recurrence (intrahepatic [n = 2] and extrahepatic [n = 20]). The MS for resected patients after transplantation was 35 months compared with 15 months for nonresected patients (P < 0.001). In multivariate analysis, the independent unfavorable factors of postrecurrence survival were alpha-fetoprotein level > 100 ng/mL at relapse (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.1; P = 0.03), intrahepatic location (HR, 1.8; 95% CI, 1.0-3.2; P = 0.05), and multifocal recurrence (HR, 1.8; 95% CI, 1.1-3.1; P = 0.04). The management including surgery (HR, 0.4; 95% CI, 0.2-0.7; P = 0.004) was identified as an independent favorable factor. In conclusion, recurrence of HCC after LT is associated with a poor prognosis. However, resection is associated with improved survival and should therefore be considered when feasible. Liver Transplantation 23 440-447 2017 AASLD.
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Affiliation(s)
| | - Marc-Antoine Allard
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 935, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Jasmijn Selten
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France
| | - Nicolas Golse
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Eric Vibert
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Antonio Sa Cunha
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - Daniel Cherqui
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Denis Castaing
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - René Adam
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 935, Institut National de la Santé et de la Recherche, Villejuif, France
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39
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 320] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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40
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Modification of immunosuppressive therapy as risk factor for complications after liver transplantation. Best Pract Res Clin Gastroenterol 2017. [PMID: 28624108 DOI: 10.1016/j.bpg.2017.03.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Management of complications post-liver transplantation (LT) includes immunosuppressive manipulations with the aim to reduce the overall burden of immunologic suppression and compensate for renal, cardiovascular, metabolic toxicities, and for the increased oncologic risk. Two approaches can be implemented to reduce immunosuppression-related adverse events: upfront schedules tailored to the pretransplant individual patient's risk profile versus downstream modifications in the event of immunosuppression-related complications. Upfront strategies are supported by evidence originating from prospective randomized trials and consist of triple/quadruple schedules whereby calcineurin inhibitors (CNI)-exposure is reduced with combination of anti-CD25 monoclonal antibodies, antimetabolites and corticosteroids. Quadruple regimens allow for staggering of CNI introduction and higher renal function in the early term, but their superiority in the long term has not yet been established. A more recent upfront schedule contemplates early (4 weeks) introduction of mammalian target of rapamycin inhibitor (mTORi) everolimus and allows for reduction of CNI up to 4 years posttransplantation. Incorporation of mTORi has the potential to prolong time to recurrence for patients with hepatocellular carcinoma. However, as suggested by the available evidence, downstream immunosuppressive manipulations are more frequently adopted in clinical practice. These encompass CNI replacement and immunosuppression withdrawal. Switching CNI to mTORi monotherapy is the option most commonly adopted to relieve renal function and compensate for posttransplant malignancies. Its impact is dependent on interval from transplantation and underlying severity of renal impairment. Introduction of mTORi is associated with longer overall survival for patients with extrahepatic posttransplant malignancies, but results are awaited for recurrences of hepatocellular carcinoma. Immunosuppression withdrawal seems feasible (70%) in very long term survivors (>10 years), but is not associated with reversal of immunosuppression-related complications. Awaiting novel immunosuppressive drug categories, integration of upfront strategies with the aim to reduce CNI-exposure and a low threshold for adjustment in the posttransplant course are both advisable to improve long-term outcomes of LT.
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41
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Scortegagna E, Karam AR, Sioshansi S, Bozorgzadeh A, Barry C, Hussain S. Hepatocellular carcinoma recurrence pattern following liver transplantation and a suggested surveillance algorithm. Clin Imaging 2016; 40:1131-1134. [DOI: 10.1016/j.clinimag.2016.07.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 06/16/2016] [Accepted: 07/05/2016] [Indexed: 12/29/2022]
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42
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Holdaas H, De Simone P, Zuckermann A. Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update. J Transplant 2016; 2016:4369574. [PMID: 27807479 PMCID: PMC5078653 DOI: 10.1155/2016/4369574] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 08/25/2016] [Indexed: 12/29/2022] Open
Abstract
Malignancy after solid organ transplantation remains a major cause of posttransplant mortality. The mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressants exerts various antioncogenic effects, and the mTOR inhibitor everolimus is licensed for the treatment of several solid cancers. In kidney transplantation, evidence from registry studies indicates a lower rate of de novo malignancy under mTOR inhibition, with some potentially supportive data from randomized trials of everolimus. Case reports and small single-center series have suggested that switch to everolimus may be beneficial following diagnosis of posttransplant malignancy, particularly for Kaposi's sarcoma and nonmelanoma skin cancer, but prospective studies are lacking. A systematic review has shown mTOR inhibition to be associated with a significantly lower rate of hepatocellular carcinoma (HCC) recurrence versus standard calcineurin inhibitor therapy. One meta-analysis has concluded that patients with nontransplant HCC experience a low but significant survival benefit under everolimus monotherapy, so far unconfirmed in a transplant population. Data are limited in heart transplantation, although observational data and case reports have indicated that introduction of everolimus is helpful in reducing the recurrence of skin cancers. Overall, it can be concluded that, in certain settings, everolimus appears a promising option to lessen the toll of posttransplant malignancy.
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Affiliation(s)
- Hallvard Holdaas
- Section of Nephrology, Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Postboks 4950 Nydalen, 0424 Oslo, Norway
| | - Paolo De Simone
- Hepatobiliary Surgery & Liver Transplantation, Azienda Ospedaliero-Universitaria Pisana, 5412 Pisa, Italy
| | - Andreas Zuckermann
- Department of Cardiac Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
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Gastaca M, Valdivieso A, Bustamante J, Fernández JR, Ruiz P, Ventoso A, Testillano M, Palomares I, Salvador P, Prieto M, Montejo M, Suárez MJ, de Urbina JO. Favorable longterm outcomes of liver transplant recipients treated de novo with once-daily tacrolimus: Results of a single-center cohort. Liver Transpl 2016; 22:1391-400. [PMID: 27434676 DOI: 10.1002/lt.24514] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 05/31/2016] [Accepted: 06/21/2016] [Indexed: 12/15/2022]
Abstract
The once-daily prolonged-release formulation of tacrolimus has been recently related with significant graft and patient mid-term survival advantages; however, practical information on the de novo administration after liver transplantation and longterm outcomes is currently lacking. This study is a 5-year retrospective analysis of a single-center cohort of liver transplant recipients treated de novo with once-daily tacrolimus (April 2008/August 2011). The study cohort consisted of 160 patients, including 23 with pretransplant renal dysfunction, with a median follow-up of 57.6 months (interquartile range, 46.6-69.0). Tacrolimus target trough levels were 5-10 ng/mL during the first 3 months after transplant, reducing progressively to <7 ng/mL after the first posttransplant year. Once-daily tacrolimus was withdrawn in 35 (21.8%) patients during follow-up, mostly due to renal dysfunction and/or metabolic syndrome. The biopsy-proven acute rejection rate was 12.5% with no cases of steroid-resistant rejection. The cumulative incidence of de novo diabetes, hypertension, and dyslipidemia were 16.9%, 31.2%, and 6.5%, respectively. Hepatocellular carcinoma recurrence rate was 2.8%. Renal function remained stable after the sixth month after transplant with a mean estimated glomerular filtration rate of 77.7 ± 19.6 mL/minute/1.73 m(2) at 5 years. None of our patients developed chronic kidney disease stage 4 or 5. Patient survival at 1, 3, and 5 years was 96.3%, 91.9%, and 88.3%, respectively. Overall survival of patients with Model for End-Stage Liver Disease (MELD) score > 25 points was not significantly different. In conclusion, our study suggests that immunosuppression based on de novo once-daily tacrolimus is feasible in routine clinical practice, showing favorable outcomes and outstanding longterm survival even in patients with high MELD scores. Liver Transplantation 22 1391-1400 2016 AASLD.
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Affiliation(s)
- Mikel Gastaca
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain. .,University of the Basque Country, Leioa, Spain.
| | - Andrés Valdivieso
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain.,University of the Basque Country, Leioa, Spain
| | - Javier Bustamante
- Liver Diseases Unit, Cruces University Hospital, Bilbao, Spain.,University of the Basque Country, Leioa, Spain
| | | | - Patricia Ruiz
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
| | - Alberto Ventoso
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
| | | | - Ibone Palomares
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
| | | | - Mikel Prieto
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
| | - Miguel Montejo
- Infectious Diseases Unit, Cruces University Hospital, Bilbao, Spain.,University of the Basque Country, Leioa, Spain
| | - María J Suárez
- Liver Diseases Unit, Cruces University Hospital, Bilbao, Spain
| | - Jorge Ortiz de Urbina
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
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44
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Khorsandi SE, Heaton N. Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence. Transl Gastroenterol Hepatol 2016; 1:25. [PMID: 28138592 DOI: 10.21037/tgh.2016.03.18] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 02/01/2016] [Indexed: 12/12/2022] Open
Abstract
The introduction of liver transplant listing criteria for hepatocellular cancer (HCC) has significantly improved oncological outcomes and survival. But despite this HCC recurrence is still problematic. There is emerging evidence that the choice of immunosuppression (IS) after transplant for HCC can influence oncological survival and HCC recurrence. The following is a short summary of what has been published on HCC recurrence with the different classes of immunosuppressive agents in present use, concluding with the possible rationalization of the use of these immunosuppressive agents in the post-transplant patient at high risk of recurrence.
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Affiliation(s)
- Shirin Elizabeth Khorsandi
- Institute of Liver Studies, King's Healthcare Partners at Denmark Hill, King's College Hospital NHSFT, London, SE5 9RS, UK
| | - Nigel Heaton
- Institute of Liver Studies, King's Healthcare Partners at Denmark Hill, King's College Hospital NHSFT, London, SE5 9RS, UK
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45
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Laparoscopic Resection of Recurrence from Hepatocellular Carcinoma after Liver Transplantation: Case Reports and Review of the Literature. Case Rep Oncol Med 2016; 2016:8946471. [PMID: 27034867 PMCID: PMC4791493 DOI: 10.1155/2016/8946471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 01/29/2016] [Accepted: 02/15/2016] [Indexed: 11/17/2022] Open
Abstract
Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) indicates a poor prognosis. Surgery is considered the only curative option for selected patients with HCC recurrence following LT. Traditionally, the preference is given to the open approach. Methods. In this report, we present two cases of laparoscopic resections (LR) for recurrent HCC after LT, performed at Oslo University Hospital, Rikshospitalet. Results. Both procedures were executed without intraoperative and postoperative adverse events. Whereas one of the patients had a recurrence one year after LR, the other patient did not have any sign of disease during 3-year follow-up. Conclusions. We argue that, in selected cases, patients with HCC recurrence following LT may benefit from LR due to its limited tissue trauma and timely start of subsequent treatment if curative resection cannot be obtained. In patients with relatively favorable prognosis, LR facilitates postoperative recovery course and avoids unnecessary laparotomy.
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46
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47
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de’Angelis N, Landi F, Carra MC, Azoulay D. Managements of recurrent hepatocellular carcinoma after liver transplantation: A systematic review. World J Gastroenterol 2015; 21:11185-11198. [PMID: 26494973 PMCID: PMC4607916 DOI: 10.3748/wjg.v21.i39.11185] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Revised: 04/06/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy (survival) and safety of treatments for recurrent hepatocellular carcinoma (HCC) in liver transplantation (LT) patients.
METHODS: Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a full-text evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.
RESULTS: Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo (range 2-132 mo). The majority of patients (67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates (42 and 18 mo, respectively). However, Sorafenib, especially when combined with mTOR, was frequently associated with severe side effects that required dose reduction or discontinuation
CONCLUSION: Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.
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48
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Mazzola A, Costantino A, Petta S, Bartolotta TV, Raineri M, Sacco R, Brancatelli G, Cammà C, Cabibbo G. Recurrence of hepatocellular carcinoma after liver transplantation: an update. Future Oncol 2015; 11:2923-36. [PMID: 26414336 DOI: 10.2217/fon.15.239] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Liver transplantation is the only curative alternative for selected patients with hepatocellular carcinoma (HCC) who are not eligible for resection and/or with decompensated cirrhosis. According to Milan criteria the 5-year survival rate is 70-85%, with a recurrence-free survival of 75%. However, HCC recurrence rate after liver transplantation remains a significant problem in the clinical practice. The prognosis in patients with HCC recurrence is poor. The treatment of choice for HCC recurrence is surgery, but it seems that a systemic treatment based on combination of an mTOR inhibitor with sorafenib can be used. Data on safety and efficacy are limited, clinical monitoring is necessary. The aim of this review is to underline the main concerns, pitfalls and warnings for these patients.
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Affiliation(s)
- Alessandra Mazzola
- Section of Gastroenterology - Di.Bi.M.I.S., University of Palermo, Palermo, Italy.,Unité Médicale de Transplantation Hépatique AP-HP, Hôpital Pitié-Salpêtrière, UPMC Paris, Paris, France
| | - Andrea Costantino
- Section of Gastroenterology - Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Salvatore Petta
- Section of Gastroenterology - Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | - Maurizio Raineri
- Section of Anesthesiology, Analgesia, Intensive Care & Emergency, Department of Biopathology, Medical & Forensic Biotechnologies (DIBIMEF), Policlinico 'P Giaccone', University of Palermo, Palermo, Italy
| | - Rodolfo Sacco
- Gastroenterology Unit, Cisanello Hospital, Pisa, Italy
| | | | - Calogero Cammà
- Section of Gastroenterology - Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology - Di.Bi.M.I.S., University of Palermo, Palermo, Italy
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49
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Follow-up Imaging After Liver Transplantation Should Take Into Consideration Primary Hepatocellular Carcinoma Characteristics. Transplantation 2015; 99:1613-8. [DOI: 10.1097/tp.0000000000000659] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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50
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Bilbao I, Salcedo M, Gómez MA, Jimenez C, Castroagudín J, Fabregat J, Almohalla C, Herrero I, Cuervas-Mons V, Otero A, Rubín A, Miras M, Rodrigo J, Serrano T, Crespo G, De la Mata M, Bustamante J, Gonzalez-Dieguez ML, Moreno A, Narvaez I, Guilera M. Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain. Liver Transpl 2015; 21:1056-65. [PMID: 25990257 DOI: 10.1002/lt.24172] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Revised: 02/26/2015] [Accepted: 05/12/2015] [Indexed: 12/12/2022]
Abstract
A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy.
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Affiliation(s)
- Itxarone Bilbao
- Unidad de Trasplante Hepático, Hospital Universitario Vall d'Hebron, Network Center for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Universidad Autónoma Barcelona, Barcelona, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Antonia Moreno
- Hospital Nuestra Señora de la Candelaria, Tenerife, Spain
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