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Piñero F, Lai Q, Costentin C, Degroote H, Schnitzbauer A, Geissler EK, Duvoux C. Validation of the R3-AFP model for risk prediction of HCC recurrence after liver transplantation in the SiLVER randomized clinical trial. Liver Transpl 2025; 31:45-57. [PMID: 39297745 DOI: 10.1097/lvt.0000000000000487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/27/2024] [Indexed: 10/23/2024]
Abstract
Explant-based models for assessing HCC recurrence after liver transplantation serve as the gold standard, guiding post-liver transplantation screening and immunosuppression adjustment. Incorporating alpha-fetoprotein (AFP) levels into these models, such as the novel R3-AFP score, has notably enhanced risk stratification. However, validation of these models in high-evidence data is mandatory. Therefore, the aim of the present research was to validate the R3-AFP score in a randomized clinical trial. We analyzed the intention-to-treat population from the 2-arm SiLVER trial (NCT00355862), comparing calcineurin-based ([calcineurin inhibitors]-Group A) versus mammalian target of rapamycin inhibitors-based (sirolimus-Group B) immunosuppression for post-liver transplantation HCC recurrence. Competing risk analysis estimated sub-hazard ratios, with testing of discriminant function and calibration. Overall, 508 patients from the intention-to-treat analysis were included (Group A, n = 256; Group B, n = 252). The R3-AFP score distribution was as follows: 42.6% low-risk (n = 216), 35.7% intermediate-risk (n = 181), 19.5% high-risk (n = 99), and 2.2% very-high-risk (n = 11) groups. The R3-AFP score effectively stratified HCC recurrence risk, with increasing risk for each stratum. Calibration of the R3-AFP model significantly outperformed other explant-based models (Milan, Up-to-7, and RETREAT), whereas discrimination power (0.75 [95% CI: 0.69; 0.81]) surpassed these models, except for the RETREAT model ( p = 0.49). Subgroup analysis showed lower discrimination power in the mammalian target of rapamycin group versus the calcineurin inhibitors group ( p = 0.048). In conclusion, the R3-AFP score accurately predicted HCC recurrence using high-quality evidence-based data, exhibiting reduced performance under mammalian target of rapamycin immunosuppression. This highlights the need for further research to evaluate surveillance schedules and adjuvant regimens.
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Affiliation(s)
- Federico Piñero
- Hepatology Section, Liver Transplant Unit, Hepatology, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Quirino Lai
- Department of Surgery, General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Charlotte Costentin
- Gastroenterology, Hepatology and GI Oncology Department, Grenoble Alpes University, Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, Digidune, Grenoble Alpes University Hospital, La Tronche, France
| | - Helena Degroote
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Andreas Schnitzbauer
- Department of Surgery, HPB and Transplant Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - Edward K Geissler
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Christophe Duvoux
- Department of Hepatology, Medical Liver Transplant Unit, Hospital Henri Mondor AP-HP, University of Paris-Est Créteil (UPEC), Créteil, France
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Alnagar A, Zakeri N, Koilias K, Faulkes RE, Brown R, Cain O, Perera MTPR, Roberts KJ, Sanabria-Mateos R, Bartlett DC, Ma YT, Sivakumar S, Shetty S, Shah T, Dasari BVM. SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation. World J Transplant 2024; 14:95849. [PMID: 39295983 PMCID: PMC11317860 DOI: 10.5500/wjt.v14.i3.95849] [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: 04/20/2024] [Revised: 05/28/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.
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Affiliation(s)
- Amr Alnagar
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nekisa Zakeri
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Konstantinos Koilias
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rosemary E Faulkes
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rachel Brown
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Owen Cain
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - M Thamara P R Perera
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith J Roberts
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rebeca Sanabria-Mateos
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Yuk Ting Ma
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shivan Sivakumar
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shishir Shetty
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Bobby V M Dasari
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
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Franchi E, Dondossola DE, Marini GMF, Iavarone M, Del Prete L, Di Benedetto C, Donato MF, Antonelli B, Lampertico P, Caccamo L. Impact of Pre-Liver Transplant Treatments on the Imaging Accuracy of HCC Staging and Their Influence on Outcomes. Cancers (Basel) 2024; 16:1043. [PMID: 38473400 DOI: 10.3390/cancers16051043] [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: 12/04/2023] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 03/14/2024] Open
Abstract
The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT.
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Affiliation(s)
- Eloisa Franchi
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Daniele Eliseo Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi, 20122 Milan, Italy
| | - Giulia Maria Francesca Marini
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi, 20122 Milan, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Luca Del Prete
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Clara Di Benedetto
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Maria Francesca Donato
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Barbara Antonelli
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Pietro Lampertico
- Department of Pathophysiology and Transplantation, Università degli Studi, 20122 Milan, Italy
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Lucio Caccamo
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
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Battistella S, Grasso M, Catanzaro E, D’Arcangelo F, Corrà G, Germani G, Senzolo M, Zanetto A, Ferrarese A, Gambato M, Burra P, Russo FP. Evolution of Liver Transplantation Indications: Expanding Horizons. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:412. [PMID: 38541138 PMCID: PMC10972065 DOI: 10.3390/medicina60030412] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/22/2024] [Accepted: 02/26/2024] [Indexed: 01/03/2025]
Abstract
Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy; (S.B.); (E.C.); (F.D.); (G.C.); (G.G.); (M.S.); (A.Z.); (A.F.); (M.G.); (P.B.)
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Yang T, Wei H, Wu Y, Qin Y, Chen J, Jiang H, Song B. Predicting histologic differentiation of solitary hepatocellular carcinoma up to 5 cm on gadoxetate disodium-enhanced MRI. Insights Imaging 2023; 14:3. [PMID: 36617583 PMCID: PMC9826771 DOI: 10.1186/s13244-022-01354-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND To establish a preoperative score based on gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators for predicting histologic differentiation of solitary HCC up to 5 cm. METHODS From July 2015 to January 2022, consecutive patients with surgically proven solitary HCC measuring ≤ 5 cm at preoperative EOB-MRI were retrospectively enrolled. All MR images were independently evaluated by two radiologists who were blinded to all clinical and pathologic information. Univariate and multivariate logistic regression analyses were performed to identify significant clinicoradiological features associated with poorly differentiated (PD) HCC, which were then incorporated into the predictive score. The predictive score was validated in an independent validation set by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. RESULTS A total of 182 patients were included, 42 (23%) with PD HCC. According to the multivariate analysis, marked hepatobiliary phase hypointensity (odds ratio [OR], 9.98), LR-M category (OR, 5.60), and serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 3.58) were incorporated into the predictive model; the predictive score achieved an AUC of 0.802 and 0.830 on the training and validation sets, respectively. The sensitivity, specificity, and accuracy of the predictive score were 66.7%, 85.7%, and 81.3%, respectively, on the training set and 66.7%, 81.0%, and 77.8%, respectively, on the validation set. CONCLUSION The proposed score integrating two EOB-MRI features and AFP level can accurately predict PD HCC in the preoperative setting.
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Affiliation(s)
- Ting Yang
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Hong Wei
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Yuanan Wu
- grid.54549.390000 0004 0369 4060Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, 610000 Sichuan China
| | - Yun Qin
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Jie Chen
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Hanyu Jiang
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China
| | - Bin Song
- grid.13291.380000 0001 0807 1581Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041 China ,Department of Radiology, Sanya People’s Hospital, Sanya, Hainan China
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6
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Wong TH, Ho CM, Hsu HH, Wu YM, Ho MC, Lee PH, Hu RH. Delayed Hepatocellular Carcinoma Recurrence After Liver Transplantation: Comprehensive Clinical Characterization of Case Series. J Hepatocell Carcinoma 2022; 9:1081-1091. [PMID: 36275405 PMCID: PMC9586169 DOI: 10.2147/jhc.s383474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 10/08/2022] [Indexed: 11/06/2022] Open
Abstract
PURPOSE Liver transplantation (LT) is the definite curative treatment for hepatocellular carcinoma (HCC), but recurrence can occur even under stringent criteria. "Delayed" HCC recurrence (>3 years after LT) is not common. Here, we present the clinical features of patients who developed delayed HCC recurrence after LT. PATIENTS AND METHODS We reviewed the data of eligible patients from February 1999 to December 2020 from medical records. RESULTS From among 195 (17%) HCC patients who received LT, 34 experienced HCC recurrence, with 5 (15%) delayed recurrence. These five explant tumors were staged T1b-T2, graded II-III, with two vascular invasion and four beyond the Milan criteria. The median time to recurrence was 6.1 years, with the longest interval being nearly 18 years. Recurrence patterns included two extrahepatic, one intrahepatic, and two mixed extrahepatic and intrahepatic recurrences. A drastic increase in serum alpha-fetoprotein levels was observed in four cases 1 year before recurrence. Management of recurrence included locoregional (surgssical resection in three, radiotherapy in three, transarterial chemoembolization in one, radiofrequency ablation in one) and systemic sorafenib use in three. Two patients died within 12-18 months, one died within 18-24 months, and two are still alive until the end of the study, with respective 13.5- and 16.5-month survival. CONCLUSION Delayed HCC recurrence could occur over 10 years. Therefore, continual surveillance for recurrence is justified, but biomarkers and intervals or intensities specific for delayed recurrence are not validated, which warrants further validation to facilitate personalized medical care.
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Affiliation(s)
- Ta-Hsiang Wong
- Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan
- School of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsao-Hsun Hsu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yao-Ming Wu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Huang Lee
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
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Salehi O, Vega EA, Kutlu OC, Lunsford K, Freeman R, Ladin K, Alarcon SV, Kazakova V, Conrad C. Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis. HPB (Oxford) 2022; 24:1100-1109. [PMID: 34969618 DOI: 10.1016/j.hpb.2021.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 11/28/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). METHODS The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. RESULTS 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. DISCUSSION HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.
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Affiliation(s)
- Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Onur C Kutlu
- Department of Surgery, University of Miami Health System, Miller School of Medicine, Miami, FL, USA
| | - Keri Lunsford
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Richard Freeman
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Keren Ladin
- Department of Occupational Therapy and Community Health, Tufts University, Boston, MA, USA
| | - Sylvia V Alarcon
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Vera Kazakova
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
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8
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Degroote H, Geerts A, Verhelst X, Van Vlierberghe H. Different Models to Predict the Risk of Recurrent Hepatocellular Carcinoma in the Setting of Liver Transplantation. Cancers (Basel) 2022; 14:cancers14122973. [PMID: 35740638 PMCID: PMC9221160 DOI: 10.3390/cancers14122973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Liver transplantation is considered the first-choice curative therapy for hepatocellular carcinoma in the early phase of the disease, when surgical resection is not possible. Even when implementing restrictive criteria to select patients for liver transplantation, there is a risk of recurrence in the transplanted liver, influencing the long-term outcome and prognosis. As it is challenging to predict the individual risk of recurrence, there is a need for validated and predictive scoring systems to use to stratify patients before and/or after liver transplantation. Most of the proposed scorings include biological markers for tumour behavior, in addition to the number and size of tumoral nodules. In this review, we discuss different published models to assess the risk of recurrent hepatocellular carcinoma after transplantation. Our aim is to refine clinical decisions about prioritization and listing for liver transplantation, to better inform patients and provide an appropriate surveillance strategy to influence their prognosis. Abstract Liver transplantation is the preferred therapeutic option for non-resectable hepatocellular carcinoma in early-stage disease. Taking into account the limited number of donor organs, liver transplantation is restricted to candidates with long-term outcomes comparable to benign indications on the waiting list. Introducing the morphometric Milan criteria as the gold standard for transplant eligibility reduced the recurrence rate. Even with strict patient selection, there is a risk of recurrence of between 8 and 20% in the transplanted liver, and this is of even greater importance when using more expanded criteria and downstaging protocols. Currently, it remains challenging to predict the risk of recurrence and the related prognosis for individual patients. In this review, the recurrence-risk-assessment scores proposed in the literature are discussed. Currently there is no consensus on the optimal model or the implications of risk stratification in clinical practice. The most recent scorings include additional biological markers for tumour behavior, such as alfa-foetoprotein, and the response to locoregional therapies, in addition to the number and diameter of tumoral nodules. The refinement of the prediction of recurrence is important to better inform patients, guide decisions about prioritization and listing and implement individualized surveillance strategies. In the future, this might also provide indications for tailored immunosuppressive therapy or inclusion in trials for adjuvant treatment.
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9
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Benkö T, König J, Theysohn JM, Schotten C, Saner FH, Treckmann J, Radunz S. Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization? Eur J Med Res 2022; 27:74. [PMID: 35619164 PMCID: PMC9134704 DOI: 10.1186/s40001-022-00708-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 05/16/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.
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Affiliation(s)
- Tamás Benkö
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Julia König
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jens M Theysohn
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Clemens Schotten
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Fuat H Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jürgen Treckmann
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Sonia Radunz
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany.
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Costentin C, Piñero F, Degroote H, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Podestá LG, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Dibenedetto F, Duque SH, Salame E, Cillo U, Marciano S, Vanlemmens C, Fagiuoli S, Burra P, Van Vlierberghe H, Cherqui D, Lai Q, Silva M, Rubinstein F, Duvoux C. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation. JHEP Rep 2022; 4:100445. [PMID: 35360522 PMCID: PMC8961219 DOI: 10.1016/j.jhepr.2022.100445] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND & AIMS Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. METHODS Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). RESULTS In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3-6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101-1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72-0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72-0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1-2 points; 15.1%), high (3-6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73-0.83). CONCLUSIONS The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. CLINICAL TRIALS REGISTRATION NCT03775863. LAY SUMMARY Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.
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Key Words
- AFP, alpha-foetoprotein
- Explants pathology
- HBV, hepatitis B virus
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- LT, liver transplantation
- Liver cancer
- Liver transplantation
- MVI, microvascular invasion
- Prediction
- R3, recurrence risk reassessment
- RETREAT, Risk Estimation of Tumour Recurrence After Transplant
- Recurrence
- SHR, sub-distribution of hazard ratio
- TC, test cohort
- TTR, time to recurrence
- VC, validation cohort
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Affiliation(s)
- Charlotte Costentin
- Grenoble Alpes University, Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, Grenoble, France
- Gastroenterology, Hepatology and GI Oncology Department, Digidune, Grenoble Alpes University Hospital, La Tronche, France
| | - Federico Piñero
- Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Helena Degroote
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | | | | | - Karim Boudjema
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou Hospital Rennes 1 University, Rennes, France
| | | | - Luis G. Podestá
- Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | | | | | - Jaime Poniachik
- Hospital Clínico de la Universidad de Chile, Santiago, Chile
| | - Fabrice Muscari
- Digestive Surgery and Transplant Unit, Hôpital Rangueil, Toulouse, France
| | - Fabrizio Dibenedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Department of General Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Sergio Hoyos Duque
- Hospital Pablo Tobón Uribe y Grupo de Gastrohepatología de la Universidad de Antioquía, Medellín, Colombia
| | | | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, Padova University Hospital, Padua, Italy
| | | | | | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padua, Italy
| | - Hans Van Vlierberghe
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Daniel Cherqui
- Hospital Paul Brousse, University of Paris, Paris, France
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Marcelo Silva
- Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Fernando Rubinstein
- Instituto de Efectividad Clínica y Sanitaria (IECS), Buenos Aires, Argentina
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Li JH, Chen T, Xing H, Li RD, Shen CH, Zhang QB, Tao YF, Wang ZX. The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2022; 22:245-252. [PMID: 35534342 DOI: 10.1016/j.hbpd.2022.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 04/18/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation (LT) is the "cure" therapy for patients with hepatocellular carcinoma (HCC). However, some patients encounter HCC recurrence after LT. Unfortunately, there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy. The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population, and to evaluate whether these patients are suitable for adjuvant targeted therapy. METHODS Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed. RESULTS A total of 201 patients were included in the study. The multivariate Cox analysis suggested that preoperative alpha fetoprotein (AFP) > 200 µg/L (HR = 2.666, 95% CI: 1.515-4.690; P = 0.001), glutamyl transferase (GGT) > 96 U/L (HR = 1.807, 95% CI: 1.012-3.224; P = 0.045), and exceeding the Hangzhou criteria (HR = 2.129, 95% CI: 1.158-3.914; P = 0.015) were independent risk factors for poor disease-free survival (DFS) in patients with HCC who underwent LT. We established an AFP-GGT-Hangzhou (AGH) scoring system based on these factors, and divided cases into high-, moderate-, and low-risk groups. The differences in overall survival (OS) and disease-free survival (DFS) rates among the three groups were significant (P < 0.05). The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria, UCSF criteria, Milan criteria, and TNM stage. Only in the high-risk group, we found that lenvatinib significantly improved prognosis compared with that of the control group (P < 0.05). CONCLUSIONS The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China. Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.
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Affiliation(s)
- Jian-Hua Li
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Tuo Chen
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Hao Xing
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Rui-Dong Li
- Department of Intensive Care Unit, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Cong-Huan Shen
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Quan-Bao Zhang
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Yi-Feng Tao
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China
| | - Zheng-Xin Wang
- Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road(M), Shanghai 200040, China.
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Savier E, Simon-Gracia L, Charlotte F, Tuffery P, Teesalu T, Scatton O, Rebollo A. Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma. Pharmaceutics 2021; 13:pharmaceutics13101631. [PMID: 34683924 PMCID: PMC8541685 DOI: 10.3390/pharmaceutics13101631] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 09/29/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022] Open
Abstract
Background: The interfering peptides that block protein–protein interactions have been receiving increasing attention as potential therapeutic tools. Methods: We measured the internalization and biological effect of four bi-functional tumor-penetrating and interfering peptides into primary hepatocytes isolated from three non-malignant and 11 hepatocellular carcinomas. Results: These peptides are internalized in malignant hepatocytes but not in non-malignant cells. Furthermore, the degree of peptide internalization correlated with receptor expression level and tumor aggressiveness levels. Importantly, penetration of the peptides iRGD-IP, LinTT1-IP, TT1-IP, and RPARPAR-IP induced apoptosis of the malignant hepatocytes without effect on non-malignant cells. Conclusion: Receptor expression levels correlated with the level of peptide internalization and aggressiveness of the tumor. This study highlights the potential to exploit the expression of tumor-penetrating peptide receptors as a predictive marker of liver tumor aggressiveness. These bi-functional peptides could be developed for personalized tumor treatment.
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Affiliation(s)
- Eric Savier
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Pitié–Salpêtrière Hospital, Sorbonne Université, 75006 Paris, France; (E.S.); (O.S.)
- Sant Antoine Research Center (CRSA), Institut Nationale de la Santé et la Recherche Médicale (Inserm), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, 75006 Paris, France
| | - Lorena Simon-Gracia
- Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50090 Tartu, Estonia; (L.S.-G.); (T.T.)
| | - Frederic Charlotte
- Department of Pathology, AP-HP, Pitié–Salpêtrière Hospital, 75006 Paris, France;
| | - Pierre Tuffery
- Biologie Fontionelle Adaptative (BFA), Unité Mixte de Recherche (UMR) 8251, Centre National de la Recherche Scientifique (CNRS) ERL U1133, Inserm, Université de Paris, 75006 Paris, France;
| | - Tambet Teesalu
- Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50090 Tartu, Estonia; (L.S.-G.); (T.T.)
- Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
| | - Olivier Scatton
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Pitié–Salpêtrière Hospital, Sorbonne Université, 75006 Paris, France; (E.S.); (O.S.)
- Sant Antoine Research Center (CRSA), Institut Nationale de la Santé et la Recherche Médicale (Inserm), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, 75006 Paris, France
| | - Angelita Rebollo
- Faculté de Pharmacie, Unité des Technologies Chimiques et Biologiques pour la Santé (UTCBS), Inserm U1267, Centre National de la Recherche Scientifique CNRS UMR8258, Université de Paris, 75006 Paris, France
- Correspondence:
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13
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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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14
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Bhatti ABH, Waheed A, Khan NA. Living Donor Liver Transplantation for Hepatocellular Carcinoma: Appraisal of the United Network for Organ Sharing Modified TNM Staging. Front Surg 2021; 7:622170. [PMID: 33553240 PMCID: PMC7859519 DOI: 10.3389/fsurg.2020.622170] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/09/2020] [Indexed: 02/05/2023] Open
Abstract
Background: In deceased donor liver transplantation (DDLT), transplant eligibility for T3-T4 HCC requires successful downstaging (DS). Living donor liver transplantation (LDLT) can be considered selectively in these patients without DS, but its role is not defined. The objective of the current study was to assess outcomes of LDLT for HCC based on UNOS staging with no prior DS. Materials and Methods: Patients who underwent LDLT for HCC (n = 262) were staged based on modified UNOS TNM staging. High-risk factors were identified and 5-year recurrence free survival was compared in patients with T2-T4 HCC. Results: Median follow-up was 30.2 (16.4-46.3) months. Recurrence rate in T1, T2, T3, T4a, and T4b HCC was 0, 10.1, 16.1, 5.9, and 37.5% (P = 0.02), respectively. On multivariate analysis, AFP > 600 ng/mL [HR:11.7, P < 0.001] and T4b HCC (macrovascular invasion) [HR = 5.6, P = 0.03] were predictors of recurrence. After exclusion of AFP > 600 ng/mL, 5-year RFS for T2, T3, and T4a HCC was 94, 86, and 92% (P = 0.3). Rate of microvascular invasion between T2 and T3 HCC was 24.3 vs. 53.6% (P = 0.005), and between T2 and T4a HCC was 24.3 vs. 36.7% (P = 0.2). Overall, 26 (19.4%) patients were overstaged and 23 (17.1%) were understaged on preoperative imaging. The 5-year RFS in patients with identical preoperative and histopathological staging was 94, 87, and 94% (P = 0.6). Conclusion: LDLT without prior DS leads to comparable survival for UNOS T2, T3, and T4a HCC as long as AFP is < 600 ng/mL.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Division of Hepato-Pancreatico-Biliary Surgery, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Anum Waheed
- Division of Hepato-Pancreatico-Biliary Surgery, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Nasir Ayub Khan
- Division of Anesthesiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
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15
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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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16
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Piñero F, Thompson M, Marín JI, Silva M. Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation: Is the current evidence applicable to these patients? World J Transplant 2020; 10:297-306. [PMID: 33312891 PMCID: PMC7708877 DOI: 10.5500/wjt.v10.i11.297] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/09/2020] [Accepted: 09/22/2020] [Indexed: 02/05/2023] Open
Abstract
Liver transplantation (LT) is one of the leading curative therapies for hepatocellular carcinoma (HCC). Despite recent optimization of transplant selection criteria, including alpha-feto protein, HCC recurrence after LT is still the leading cause of death in these patients. During the last decades, effective systemic treatments for HCC, including tyrosine kinase inhibitors and immunotherapy, have been approved. We describe the clinical scenario of a patient with recurrence of HCC five years after LT, who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical setting. In this opinion review, we detail first and second-line systemic treatment options, focusing on those feasible for patients with recurrent HCC after LT. Several trials have evaluated new drugs to treat HCC patients in first and second-line therapy, but patients with recurrent HCC after LT have been excluded from these trials. Consequently, most of the evidence comes from observational retrospective studies. Whether tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients, due to a relative contraindication for immunotherapy, may be clarified in the near future.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires B1629HJ, Argentina
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires B1629HJ, Argentina
| | - Marcos Thompson
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
| | - Juan Ignacio Marín
- Hepatology and Liver Transplantation Unit, Hospital Pablo Tobón Uribe, Medellín 240, Colombia
| | - Marcelo Silva
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires B1629HJ, Argentina
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17
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Posttransplant Management of Recipients Undergoing Liver Transplantation for Hepatocellular Carcinoma. Working Group Report From the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1143-1149. [PMID: 32217940 DOI: 10.1097/tp.0000000000003196] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Although liver transplantation (LT) is the best treatment for patients with localized hepatocellular carcinoma (HCC), recurrence occurs in 6%-18% of patients. Several factors, particularly morphological criteria combined with dynamic parameters, known before LT modify this risk and combined in prediction models may be used to stratify patients at need of variable surveillance strategies. Additional variables though likely explain differences in recurrence rates in patients with the same pre-LT HCC status. One of these variables is possibly immunosuppression (IS). Once recurrence takes place, management is highly heterogenous. Within the International Liver Transplantation Society Consensus Conference on Liver Transplant Oncology, working group 4 aim was to analyze the data regarding posttransplant management of recipients undergoing LT for HCC. Three areas of research were considered: (1) cancer prediction models and surveillance strategies; (2) tailored IS for cancer recipients; and (3) new adjuvant therapies for HCC recurrence. Following formulation of several questions, a literature search was undertaken with abstract review followed by article retrieval and full-data extraction. The grading of recommendations assessment, development and evaluation (GRADE) system was used for evidence rating incorporating strength of recommendation and quality of evidence.
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18
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Piñero F, Tanno M, Aballay Soteras G, Tisi Baña M, Dirchwolf M, Fassio E, Ruf A, Mengarelli S, Borzi S, Fernández N, Ridruejo E, Descalzi V, Anders M, Mazzolini G, Reggiardo V, Marciano S, Perazzo F, Spina JC, McCormack L, Maraschio M, Lagues C, Gadano A, Villamil F, Silva M, Cairo F, Ameigeiras B. Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma. Ann Hepatol 2020; 19:546-569. [PMID: 32593747 DOI: 10.1016/j.aohep.2020.06.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 06/05/2020] [Accepted: 06/10/2020] [Indexed: 02/08/2023]
Abstract
The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina.
| | - Mario Tanno
- Hospital Centenario de Rosario, Santa Fe, Argentina
| | | | - Matías Tisi Baña
- Internal Medicine and Epidemiology Department, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Andrés Ruf
- Hospital Privado de Rosario, Santa Fe, Argentina
| | | | - Silvia Borzi
- Instituto Rossi, La Plata, Buenos Aires, Argentina
| | | | - Ezequiel Ridruejo
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina; Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Ciudad de Buenos Aires, Argentina
| | | | | | - Guillermo Mazzolini
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | | | | | | | | | - Cecilia Lagues
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Marcelo Silva
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
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Piñero F, Boin I, Chagas A, Quiñonez E, Marciano S, Vilatobá M, Santos L, Anders M, Hoyos Duque S, Soares Lima A, Menendez J, Padilla M, Poniachik J, Zapata R, Maraschio M, Chong Menéndez R, Muñoz L, Arufe D, Figueroa R, Mendizabal M, Hurtado Gomez S, Stucchi R, Maccali C, Vergara Sandoval R, Bermudez C, McCormack L, Varón A, Gadano A, Mattera J, Rubinstein F, Carrilho F, Silva M. Direct-Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait-List Progression or Posttransplant Recurrence. Liver Transpl 2020; 26:640-650. [PMID: 32133773 DOI: 10.1002/lt.25744] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 12/23/2019] [Accepted: 01/19/2020] [Indexed: 12/17/2022]
Abstract
The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network, Pilar, Argentina
| | - Ilka Boin
- Hospital das Clínicas Universidade Estadual do Campiñas (UNICAMP), Sao Paulo, Brazil
| | - Aline Chagas
- Hospital das Clínicas University of São Paulo School of Medicine, Sao Paulo, Brazil
| | | | | | - Mario Vilatobá
- Instituto de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, México
| | | | | | - Sergio Hoyos Duque
- Hospital Tobón Uribe, Medellín, y Grupo de Gastrohepatología, Universidad de Antioquia, Antioquia, Colombia
| | | | | | | | | | - Rodrigo Zapata
- Clínica Alemana, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile
| | | | | | - Linda Muñoz
- Hospital Universitario "Dr. José E. González,", Monterrey, Mexico
| | - Diego Arufe
- Sanatorio Sagrado Corazón, Buenos Aires, Argentina
| | | | - Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network, Pilar, Argentina
| | - Sahara Hurtado Gomez
- Instituto de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, México
| | - Raquel Stucchi
- Hospital das Clínicas Universidade Estadual do Campiñas (UNICAMP), Sao Paulo, Brazil
| | - Claudia Maccali
- Hospital das Clínicas University of São Paulo School of Medicine, Sao Paulo, Brazil
| | | | - Carla Bermudez
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | | | - Adrián Gadano
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | | | - Flair Carrilho
- Hospital das Clínicas University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Marcelo Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network, Pilar, Argentina
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20
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Al-Ameri AAM, Wei X, Wen X, Wei Q, Guo H, Zheng S, Xu X. Systematic review: risk prediction models for recurrence of hepatocellular carcinoma after liver transplantation. Transpl Int 2020; 33:697-712. [PMID: 31985857 DOI: 10.1111/tri.13585] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/10/2019] [Accepted: 01/21/2020] [Indexed: 12/17/2022]
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a significant clinical problem associated with poor surgical outcomes. This study aims to summarize the current evidence on risk prediction models of HCC recurrence after LT. PubMed and EMBASE were searched to May 25, 2019, for relevant articles. Studies originally designed to develop or validate a risk prediction model for HCC recurrence after LT were included. Two independent authors summarized the study characteristics and evaluated the risk of bias and applicability concerns in the included studies. From 26 included studies, 18 original risk prediction models were determined, but only five models were externally validated. The average number of predictors involved in the construction of risk models was three. The most frequently employed predictors were alpha-fetoprotein, tumor size, vascular invasion, tumor number, tumor differentiation, and neutrophil-lymphocyte ratio. Most studies showed good discriminatory performance (AUC >0.75). The overall quality of the included studies was generally low. Most of the original models lacked the highly recommended external and prospective validation in diverse populations. The AFP model was the well-validated preoperative risk model that can stratify patients into high- and low-risk groups.
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Affiliation(s)
- Abdulahad Abdulrab Mohammed Al-Ameri
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xue Wen
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Haijun Guo
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
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21
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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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22
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Sotiropoulos GC, Malago M, Machairas N, Fouzas I, Paul A. AGMA Score: A Novel Prognostic Score for Patients Undergoing Liver Transplant for Hepatocellular Carcinoma. Transplant Proc 2019; 51:1923-1925. [PMID: 31399177 DOI: 10.1016/j.transproceed.2019.05.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 04/29/2019] [Accepted: 05/07/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) in cirrhosis represents one of the leading indications for liver transplant. In an effort to expand the listing criteria, a variety of scoring systems have been suggested, mainly based on the tumor number/size criterion. The objective of our study was to evaluate the feasibility of proposing a transplant score for HCC excluding the tumor number/size criterion. PATIENTS AND METHODS Data corresponding to patients who received transplants because of HCC were reviewed for the purposes of this study. Deceased donor and living donor liver transplants were included. Demographic, clinical and tumor-related parameters were evaluated. Uni- and multivariate regression analyses and survival analysis were performed. RESULTS One hundred patients were included in the study. Fifty-five patients underwent deceased donor liver transplant, and 45 patients received living donor liver transplants. Tumor differentiation (G1/2 vs G3), alpha-fetoprotein levels (AFP), recipient age, and recipient laboratory Model for End-Stage Liver Disease Score (MELD) showed statistical significance. A scoring system was developed, with prognostic points assigned as follows: age 60 years or younger:age older than 60 years = 1:0 points, tumor grading well or moderate:tumor grading poor = 1:0 points, MELD score ≤22:MELD score >22 = 1:0 points, and AFP level ≤400 ng/mL:AFP level >400 ng/mL = 1:0 points. This stratification delineated 3 separate population samples corresponding to patients with scores of 4, 3, and 1 to 2, respectively. The calculated 5-year survival for scores 4, 3, and 1 to 2 was 76%, 47%, and 20%, respectively (P < .001). CONCLUSION The AGMA score (age, grading, MELD, AFP) showed prognostic value in this single-center analysis and may find clinical implication avoiding the tumor number/size criterion.
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Affiliation(s)
- Georgios C Sotiropoulos
- Department of General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
| | - Massimo Malago
- Department of General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Nikolaos Machairas
- Department of General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Ioannis Fouzas
- Department of General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Andreas Paul
- Department of General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
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23
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Costentin CE, Bababekov YJ, Zhu AX, Yeh H. Is It Time to Reconsider the Milan Criteria for Selecting Patients With Hepatocellular Carcinoma for Deceased-Donor Liver Transplantation? Hepatology 2019; 69:1324-1336. [PMID: 30229978 DOI: 10.1002/hep.30278] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 08/31/2018] [Indexed: 12/12/2022]
Abstract
Liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC) because it removes tumor as well as the underlying cirrhotic liver. Because of a global organ shortage, LT for patients with HCC is limited to patients with expected survival comparable to that of nonmalignant indications. Therefore, identifying patients with lower rates of HCC recurrence and higher rates of survival is critical. International guidelines have considered the Milan Criteria (MC) the standard for selecting patients with HCC for deceased-donor LT (DDLT). However, several alternative criteria have been reported in the Western world. Interestingly, the two most recent models combining α-fetoprotein level, number of nodules, and size of the largest nodule have been shown to outperform MC in identifying patients with low risk of HCC recurrence or those who will survive for 5 years after liver transplantation. In addition, new models overcome limitations of MC in improving classification of high- versus low-risk patients with HCC for DDLT. These recent scoring systems also provide clinicians with user-friendly tools to better identify patients at lower risk of recurrence. Conclusion: Although most Western countries still select patients based on MC, there is a mounting change in recent practice patterns regarding the selection of patients with HCC for DDLT. Herein, we describe how alternative criteria should lead to reconsideration of MC as it applies to selecting patients with HCC for DDLT in international guidelines.
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Affiliation(s)
| | - Yanik J Bababekov
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Andrew X Zhu
- Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Heidi Yeh
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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24
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Comparison of 3 Explant-Based Prognostic Models as Predictors of Hepatocellular Carcinoma Recurrence After Liver Transplantation: Analysis of Our Experience. Transplant Proc 2019; 51:80-82. [DOI: 10.1016/j.transproceed.2018.03.132] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 03/15/2018] [Indexed: 11/19/2022]
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25
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Piñero F, Costa P, Boteon YL, Duque SH, Marciano S, Anders M, Varón A, Zerega A, Poniachik J, Soza A, Machaca MP, Menéndez J, Zapata R, Vilatoba M, Muñoz L, Maraschio M, Fauda M, McCormack L, Gadano A, Boin IS, García JHP, Silva M. Results of Liver Transplantation for Hepatocellular Carcinoma in a Multicenter Latin American Cohort Study. Ann Hepatol 2018; 17:256-267. [PMID: 29469048 DOI: 10.5604/01.3001.0010.8648] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Heterogeneous data has been reported regarding liver transplantation (LT) for hepatocellular carcinoma (HCC) in Latin America. We aimed to describe treatment during waiting list, survival and recurrence of HCC after LT in a multicenter study from Latin America. MATERIAL AND METHODS Patients with HCC diagnosed prior to transplant (cHCC) and incidentally found in the explanted liver (iHCC) were included. Imaging-explanted features were compared in cHCC (non-discordant if pre and post-LT were within Milan, discordant if pre-LT was within and post-LT exceeding Milan). RESULTS Overall, 435 patients with cHCC and 92 with iHCC were included. At listing, 81% and 91% of cHCC patients were within Milan and San Francisco criteria (UCSF), respectively. Five-year survival and recurrence rates for cHCC within Milan, exceeding Milan/within UCSF and beyond UCSF were 71% and 16%; 66% and 26%; 46% and 55%, respectively. Locoregional treatment prior to LT was performed in 39% of cHCC within Milan, in 53% beyond Milan/within UCSF and in 83% exceeding UCSF (p < 0.0001). This treatment difference was not observed according to AFP values (≤100, 44%; 101-1,000, 39%, and > 1,000 ng/mL 64%; p = 0.12). Discordant imaging-explanted data was observed in 29% of cHCC, showing lower survival HR 2.02 (CI 1.29; 3.15) and higher recurrence rates HR 2.34 when compared to AFP <100 ng/mL. Serum AFP > 1,000 ng/mL at listing was independently associated with a higher 5-year recurrence rate and a HR of 3.24 when compared to AFP <100 ng/mL. CONCLUSION Although overall results are comparable to other regions worldwide, pre-LT treatment not only considering imaging data but also AFP values should be contemplated during the next years.
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Affiliation(s)
- Federico Piñero
- Hospital Universitario Austral. Austral University, Faculty of Medicine. Argentina
| | - Paulo Costa
- Hospital Federal University of Ceará, Brazil
| | - Yuri L Boteon
- Hospital de Clinicas, State University of Campinas, Brazil
| | - Sergio Hoyos Duque
- Hospital Pablo Tobón Uribe and Gastroenterology group from Universidad de Antioquía, Medellín, Colombia
| | | | | | - Adriana Varón
- Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | | | | | | | | | | | - Rodrigo Zapata
- Clinica Alemana de Santiago, Universidad del Desarrollo, Chile
| | | | | | | | - Martín Fauda
- Hospital Universitario Austral. Austral University, Faculty of Medicine. Argentina
| | | | | | - Ilka Sf Boin
- Hospital de Clinicas, State University of Campinas, Brazil
| | | | - Marcelo Silva
- Hospital Universitario Austral. Austral University, Faculty of Medicine. Argentina. On behalf of the Latin American Liver Research, Education and Awareness Network (LALREAN)
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26
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Jin YJ, Cho SG, Lee KY, Kim JM, Lee JW. Association between relative liver enhancement on gadoxetic acid enhanced magnetic resonance images and histologic grade of hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e7580. [PMID: 28746206 PMCID: PMC5627832 DOI: 10.1097/md.0000000000007580] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We evaluated the association between histologic grade of hepatocellular carcinoma (HCC) and degree of HCC enhancement on Gd-EOB-DTPA (Gadoxetic acid, Primovist)-enhanced magnetic resonance images (MRI) in HCC patients.A total of 121 patients who underwent curative surgical resection for HCC at our institution between January 2012 and March 2015 were retrospectively analyzed. Gadoxetic acid enhanced MRI was performed in all patients before surgery. Signal intensities of HCC and peri-HCC areas were measured using regions of interest. Relative intensity ratios of HCC lesions versus the surrounding non-HCC areas on unenhanced images (precontrast ratio) and on hepatobiliary phase images (postcontrast ratio) were calculated. Relative liver enhancement (RLE) ratios (post-contrast ratio/pre-contrast ratio) were also calculated. The Edmondson-Steiner (E-S) grading system was used to histologically grade HCC.E-S grades I, II, III, and IV were observed in 2 (1.7%), 14 (11.6%), 54 (44.6%), and 51 (42.1%) of the patients, respectively. For E-S grades I/II (n = 16), III (n = 54), and IV (n = 51), mean RLE (%) were 85.5, 84.9, and 71.2, respectively (P = .01), and for E-S grades I-III (n = 70) and IV (n = 51), mean RLE (%) were 85.1 and 71.2, respectively (P < .01). Barcelona Clinic Liver Cancer (BCLC) stage A (vs 0) (odds ratio 4.38, P = .03) and mean RLE (odds ratio 0.05, P < .01) were found to predict E-S grade IV.E-S grade IV was associated with a low level mean RLE in the gadoxetic acid enhanced MR images of HCC patients.
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Affiliation(s)
| | | | | | - Joon Mee Kim
- Department of Pathology, Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
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27
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Costentin CE, Amaddeo G, Decaens T, Boudjema K, Bachellier P, Muscari F, Salamé E, Bernard PH, Francoz C, Dharancy S, Vanlemmens C, Radenne S, Dumortier J, Hilleret MN, Chazouillères O, Pageaux GP, Calderaro J, Laurent A, Roudot-Thoraval F, Duvoux C. Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models. Liver Int 2017; 37:717-726. [PMID: 28199760 DOI: 10.1111/liv.13388] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 02/08/2017] [Indexed: 12/17/2022]
Abstract
AIM Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. METHODS Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. RESULTS Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17). CONCLUSION Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.
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Affiliation(s)
| | | | - Thomas Decaens
- Service d'hépatologie, CHU Grenoble Alpes, Grenoble, France
| | - Karim Boudjema
- Service de Chirurgie digestive, Hôpital Pontchaillou, Rennes, France
| | | | - Fabrice Muscari
- Service de Chirurgie digestive, Hôpital Rangueil, Toulouse, France
| | - Ephrem Salamé
- Service de Chirurgie digestive, CHU de Tours, Chambray-lès-Tours, France
| | | | | | | | | | - Sylvie Radenne
- Service d'hépatologie, Hôpital Lyon Croix Rousse, Lyon, France
| | - Jérôme Dumortier
- Service d'hépatologie, Hospices Civiles de Lyon, Hôpital Edouard Herriot, Lyon, France
| | | | | | | | - Julien Calderaro
- Département de Pathologie, Hôpital Henri Mondor, Créteil, France
| | - Alexis Laurent
- Service de Chirurgie digestive, Hôpital Henri Mondor, Créteil, France
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28
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Piñero F, Carrihlo FJ, Silva MO. Predictive models for recurrence risk of hepatocellular carcinoma after liver transplantation: Still an unmet need. Liver Int 2017; 37:648-650. [PMID: 28453922 DOI: 10.1111/liv.13417] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
See Article on Page 717
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Affiliation(s)
- Federico Piñero
- Liver Transplant and Hepatology Unit, Faculty of Biomedical Science, Hospital Universitario Austral, Austral University, Pilar, Argentina
| | - Flair J Carrihlo
- Gastroenterology and Hepatology, Hospital da Clinicas, University of Sao Paulo School of Medicine, State University of Sao Paulo, Sao Paulo, Brazil
| | - Marcelo O Silva
- Liver Transplant and Hepatology Unit, Faculty of Biomedical Science, Hospital Universitario Austral, Austral University, Pilar, Argentina
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29
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Guerrini GP, Pinelli D, Di Benedetto F, Marini E, Corno V, Guizzetti M, Aluffi A, Zambelli M, Fagiuoli S, Lucà MG, Lucianetti A, Colledan M. Predictive value of nodule size and differentiation in HCC recurrence after liver transplantation. Surg Oncol 2016; 25:419-428. [DOI: 10.1016/j.suronc.2015.09.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 09/13/2015] [Indexed: 01/11/2023]
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30
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Li X, Zhang K, Shi Y, Wang F, Meng X. Correlations between the minimum and mean apparent diffusion coefficient values of hepatocellular carcinoma and tumor grade. J Magn Reson Imaging 2016; 44:1442-1447. [PMID: 27228086 DOI: 10.1002/jmri.25323] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Revised: 05/07/2016] [Accepted: 05/11/2016] [Indexed: 12/27/2022] Open
Affiliation(s)
- Xubin Li
- Department of Radiology; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy; Tianjin China
| | - Kun Zhang
- Department of Radiology; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy; Tianjin China
| | - Yan Shi
- Department of Radiology; Guiyang First People's Hospital; Guizhou China
| | - Fengkui Wang
- Department of Radiology; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy; Tianjin China
| | - Xiangfu Meng
- Department of Radiology; Linyi Traditional Chinese Medicine Hospital; Shandong China
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Li R, Yan F, Liu L, Li H, Ren B, Hui Z, Ren X. Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report. Oncol Lett 2016; 11:1885-1888. [PMID: 26998094 DOI: 10.3892/ol.2016.4109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 11/30/2015] [Indexed: 12/13/2022] Open
Abstract
Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the most lethal cancers worldwide. Immunotherapy based on the direct attack of tumor cells and the stimulation of an antitumor immune response may represent a novel strategy to control HCC recurrence and metastasis. The present study reports the case of a patient with HCC, and describes the safety and feasibility of successful administration with a mass of autologous activated T cells on numerous occasions subsequent to liver transplantation (LT), in order to kill the residual tumor cells and stimulate the immune system. A large number of infused activated T cells may pose a potential risk to the allograft. However, no acute or delayed adverse effects of cytokine-induced killer cell (CIK) therapy, or other symptoms of secondary acute host-versus-graft disease (HVGD), were observed. These observations demonstrate the relatively low toxicity of CIK infusion to a patient that has undergone LT, and more importantly, they demonstrate the feasibility of this immunotherapy for the patient, following successful LT.
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Affiliation(s)
- Runmei Li
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; Biotherapy Center, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
| | - Fang Yan
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
| | - Liang Liu
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; Biotherapy Center, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
| | - Hui Li
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; Biotherapy Center, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
| | - Baozhu Ren
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; Biotherapy Center, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
| | - Zhenzhen Hui
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; Biotherapy Center, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
| | - Xiubao Ren
- Department of Immunology, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; Biotherapy Center, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China
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Di Costanzo GG, Tortora R. Intermediate hepatocellular carcinoma: How to choose the best treatment modality? World J Hepatol 2015; 7:1184-1191. [PMID: 26019734 PMCID: PMC4438493 DOI: 10.4254/wjh.v7.i9.1184] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/16/2014] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma (HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large (> 5 cm) solitary HCC should be firstly considered for liver resection (LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization (TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization (TARE)-plus percutaneous ablation] is “a priori” preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases (patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be “patient-tailored” and made by a multidisciplinary team.
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Prognostic value of glypican-3 in patients with HBV-associated hepatocellular carcinoma after liver transplantation. Hepatobiliary Pancreat Dis Int 2015; 14:157-63. [PMID: 25865688 DOI: 10.1016/s1499-3872(15)60349-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Glypican-3 (GPC-3) is frequently overexpressed in hepatocellular carcinoma (HCC). Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy. However, its prognostic value in patients with HBV-associated HCC after liver transplantation (LT) is not clear. The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT. METHODS A cohort of 104 HCC patients with HBV-associated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohistochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS GPC-3 was expressed in samples from 74 (71.2%) of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size (P=0.004), encapsulation (P=0.018), pathological stage (P=0.027), portal vein invasion (P=0.043), tumor differentiation (P=0.002) and the Milan criteria (P=0.016). The 5-year survival rate and disease-free survival rate of patients with GPC-3-positive were lower than those (38.2% vs 75.4%, P<0.001; 30.8% vs 69.7%, P=0.001) of patients with GPC-3-negative. Multivariate Cox-regression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate (P=0.031) and disease-free survival rate (P=0.047), together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein. CONCLUSION GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.
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Wang LY, Zheng SS, Xu X, Wang WL, Wu J, Zhang M, Shen Y, Yan S, Xie HY, Chen XH, Jiang TA, Chen F. A score model for predicting post-liver transplantation survival in HBV cirrhosis-related hepatocellular carcinoma recipients: a single center 5-year experience. Hepatobiliary Pancreat Dis Int 2015; 14:43-49. [PMID: 25655289 DOI: 10.1016/s1499-3872(15)60335-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prognostic prediction of liver transplantation (LT) guides the donor organ allocation. However, there is currently no satisfactory model to predict the recipients' outcome, especially for the patients with HBV cirrhosis-related hepatocellular carcinoma (HCC). The present study was to develop a quantitative assessment model for predicting the post-LT survival in HBV-related HCC patients. METHODS Two hundred and thirty-eight LT recipients at the Liver Transplant Center, First Affiliated Hospital, Zhejiang University School of Medicine between 2008 and 2013 were included in this study. Their post-LT prognosis was recorded and multiple risk factors were analyzed using univariate and multivariate analyses in Cox regression. RESULTS The score model was as follows: 0.114X(Child-Pugh score)-0.002X(positive HBV DNA detection time)+0.647X(number of tumor nodules)+0.055X(max diameter of tumor nodules)+0.231XlnAFP+0.437X(tumor differentiation grade). The receiver operating characteristic curve analysis showed that the area under the curve of the scoring model for predicting the post-LT survival was 0.887. The cut-off value was 1.27, which was associated with a sensitivity of 72.5% and a specificity of 90.7%, respectively. CONCLUSION The quantitative score model for predicting post-LT survival proved to be sensitive and specific.
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Affiliation(s)
- Li-Ying Wang
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Health; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Li WX, Li Z, Gao PJ, Gao J, Zhu JY. Histological differentiation predicts post-liver transplantation survival time. Clin Res Hepatol Gastroenterol 2014; 38:201-8. [PMID: 24388339 DOI: 10.1016/j.clinre.2013.11.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2013] [Revised: 10/01/2013] [Accepted: 11/12/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Although liver transplantation is the most effective long-term treatment for hepatocellular carcinoma (HCC), the recurrence of HCC remains an issue. Current research examining recurrence after liver transplantation primarily focuses on patients' clinical characteristics. There is no consensus regarding the factors that may relate to predict the survival time and recurrence rates for patients with hepatitis B virus (HBV)-associated HCC transplantation using clinicopathological analysis. METHODS One hundred and three patients with HCC were enrolled in the study. All data were collected from the China Liver Transplant Registry. The independent variables were as follows: age, gender, etiology, preoperative alpha-fetoprotein (AFP) levels, body mass index (BMI), Model for End-stage Liver Disease (MELD) and Child-Pugh scores, primary tumor, regional nodes, metastasis (TNM) classification, number of tumors, the size for the largest tumor, multifocality, portal vein tumor thrombosis and histological differentiation, and prognostic staging score criteria (Milan criteria). All of the patients had previously undergone liver transplantation. Univariate and multivariate analysis were used to determine the factors related to the survival time and recurrence. RESULTS After a median follow-up period of 41.05±28.90 months, the 5-year overall survival rate was 46.60%, and the 5-year recurrence rate was 45.63%. Forty-seven patients (45.63%) died due to HCC recurrence during the follow-up period. Patients within Milan criteria exhibited excellent post-transplantation survival times. Univariate analysis suggested that patients with poor tumor differentiation, AFP≥400ng/ml, portal vein tumor thrombosis, and TNM staging of I+II had significantly predicted shorter survival times and higher recurrence than patients displaying good or moderate tumor differentiation, AFP<400ng/ml, no portal vein thrombosis and TNM staging of III+IV for HBV-associated HCC. However, multivariate analysis revealed that poor tumor differentiation and high serum AFP were associated with a shorter survival time. Moreover, poor tumor differentiation suggested high recurrence. In addition, patients' survival time with AFP<400ng/ml was longer than that of patients with AFP≥400ng/ml even in patients with HCC beyond Milan criteria. CONCLUSIONS Tumor biological characteristics especially histological differentiation and serum AFP level should be considered before performing liver transplantation (LT) for patients with HBV-associated HCC. Furthermore, the AFP level and histological differentiation provide a new method for assessing HCC patient survival time after LT. Histological differentiation independently predicted post-transplantation survival time and recurrence rate for patients with HBV-associated HCC.
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Affiliation(s)
- Wen Xia Li
- Department of Hepatobiliary Surgery, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, 010-88324175 Beijing, People's Republic of China.
| | - Zhao Li
- Department of Hepatobiliary Surgery, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, 010-88324175 Beijing, People's Republic of China.
| | - Peng Ji Gao
- Department of Hepatobiliary Surgery, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, 010-88324175 Beijing, People's Republic of China.
| | - Jie Gao
- Department of Hepatobiliary Surgery, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, 010-88324175 Beijing, People's Republic of China.
| | - Ji Ye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, 010-88324175 Beijing, People's Republic of China.
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Wu XY, Qiu YD, Ding YT. Criteria for case selection and perioperative management in liver transplantation for primary liver carcinoma. Shijie Huaren Xiaohua Zazhi 2013; 21:3876-3880. [DOI: 10.11569/wcjd.v21.i34.3876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To summarize our experience with the treatment of hepatocellular carcinoma (HCC) by liver transplantation.
METHODS: The clinic data for 46 HCC patients treated by liver transplantation from November 2005 to January 2011 were analyzed retrospectively. The effects of factors such as the number and diameter of tumors, vascular invasion and perioperative management on the prognosis were analyzed.
RESULTS: Piggy-back liver transplantation was performed in 42 cases, and conventional liver transplantation was performed in 4 cases. Liver transplantation was successful in 45 cases, and 19 patients are still alive. The longest tumor-free survival was 63 mo. Recurrence occurred in 2 patients at 2 and 17 mo after operation, respectively.
CONCLUSION: Portal vein invasion should be the contradiction for liver transplantation. Modified piggy-back liver transplantation could be the choice for the treatment of primary liver carcinoma. Perioperative management with cool-tip radiofrequency ablation (RFA) is beneficial to the prognosis.
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Bolondi L, Cillo U, Colombo M, Craxì A, Farinati F, Giannini EG, Golfieri R, Levrero M, Pinna AD, Piscaglia F, Raimondo G, Trevisani F, Bruno R, Caraceni P, Ciancio A, Coco B, Fraquelli M, Rendina M, Squadrito G, Toniutto P. Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis 2013; 45:712-723. [PMID: 23769756 DOI: 10.1016/j.dld.2013.01.012] [Citation(s) in RCA: 141] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 01/16/2013] [Indexed: 12/11/2022]
Abstract
Patients with hepatocellular carcinoma should be managed with a multidisciplinary approach framed in a network where all the diagnostic techniques and therapeutic resources are available in order to provide the optimal level of care. Given this assumption, the Coordinating Committee of the Italian Association for the Study of the Liver nominated a panel of experts to elaborate practical recommendations for the multidisciplinary management of hepatocellular carcinoma aiming to provide: (1) homogeneous and efficacious diagnostic and staging work-up, and (2) the best treatment choice tailored to patient status and tumour stage at diagnosis. The 2010 updated American Association for the Study of Liver Disease Guidelines for hepatocellular carcinoma were selected as the reference document. For each management issue, the American Association for the Study of Liver Disease recommendations were briefly summarised and discussed, according to both the scientific evidence published after their release and the clinical expertise of the Italian centres taking care of these patients. The Italian Association for the Study of the Liver expert panel recommendations are finally reported.
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Han DH, Choi GH, Kim KS, Choi JS, Park YN, Kim SU, Park JY, Ahn SH, Han KH. Prognostic significance of the worst grade in hepatocellular carcinoma with heterogeneous histologic grades of differentiation. J Gastroenterol Hepatol 2013; 28:1384-1390. [PMID: 23517197 DOI: 10.1111/jgh.12200] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Although tumor differentiation is a known prognostic factor after the treatment of hepatocellular carcinoma (HCC), there have not been any studies on the prognostic significance of tumor differentiation in HCC with heterogeneous histologic grades. In this study, we attempted to ascertain whether the major or the worst grade in mixed histologic type HCC determines the prognosis after liver resection. METHODS From January 1996 to March 2010, a total of 724 patients underwent curative resection of HCC at Yonsei University Health System, Korea. Of those, we excluded 99 patients who had total necrosis because of previous treatment. Among the remaining 625 patients, we compared the homogeneous moderately differentiated group (HG2, n = 241), mixed histologic grades with the worst component as poorly differentiated group (M2, n = 142), and homogeneous poorly differentiated group (HG3, n = 156). The clinicopathologic features, disease-free survival (DFS) and overall survival (OS) in each group were analyzed. RESULTS The DFS and OS were significantly lower in M2 than in HG2 (P = 0.004 and 0.025, respectively) whereas those of M2 were not significantly different from HG3. There were no significant differences in the clinicopathologic features of each group except that microvascular invasion was more frequently observed in M2 than in HG2. On multivariate analysis, being in the worst histologic group (M2 and HG3) was an independent poor prognostic factor for DFS and OS (P = 0.028 and < 0.001, respectively). CONCLUSIONS In patients with advanced histologic grade, the worst histologic grade may determine the prognosis after curative resection of HCC.
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Affiliation(s)
- Dai Hoon Han
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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Current World Literature. Curr Opin Oncol 2012; 24:197-202. [DOI: 10.1097/cco.0b013e32835164ff] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Balci D, Dayangac M, Yaprak O, Akin B, Duran C, Killi R, Yuzer Y, Tokat Y. Living donor liver transplantation for hepatocellular carcinoma: a single center analysis of outcomes and impact of different selection criteria. Transpl Int 2011; 24:1075-83. [DOI: 10.1111/j.1432-2277.2011.01311.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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