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Ho K, Chan A. Liver transplantation for hepatocellular carcinoma: Current status in Hong Kong, China. Hepatobiliary Pancreat Dis Int 2025; 24:45-49. [PMID: 39307663 DOI: 10.1016/j.hbpd.2024.09.005] [Citation(s) in RCA: 1] [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] [Received: 07/04/2024] [Accepted: 09/02/2024] [Indexed: 04/25/2025]
Abstract
With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, China that have enabled preoperative prognostication for judicious patient selection, downstaging therapy to definitive treatment, and postoperative therapies that have provided a growing role for liver transplantation in patients with more advanced hepatocellular carcinoma.
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Affiliation(s)
- Karin Ho
- Liver Transplant Center, Queen Mary Hospital, Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Albert Chan
- Liver Transplant Center, Queen Mary Hospital, Department of Surgery, The University of Hong Kong, Hong Kong, China.
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Lee VHF, Vardhanabhuti V, Wong TCL, Lam KO, Choi HCW, Chiu KWH, Ho PPY, Leung DKC, Szeto MHM, Choi KF, Chan SC, Leung TW, Khong PL, Lo CM. Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial. JAMA Netw Open 2024; 7:e2415998. [PMID: 38857045 PMCID: PMC11165380 DOI: 10.1001/jamanetworkopen.2024.15998] [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: 12/17/2023] [Accepted: 04/09/2024] [Indexed: 06/11/2024] Open
Abstract
Importance Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.
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Affiliation(s)
- Victor Ho-Fun Lee
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Varut Vardhanabhuti
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tiffany Cho-Lam Wong
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Ka-On Lam
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Horace Cheuk-Wai Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Keith Wan-Hang Chiu
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Patty Pui-Ying Ho
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | | | - Matthew Ho-Man Szeto
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Kwok-Fung Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - See-Ching Chan
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - To-Wai Leung
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Pek-Lan Khong
- Department of Diagnostic Radiology and Clinical Imaging Research Center, National University of Singapore, Singapore
| | - Chung-Mau Lo
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
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Wong TC, Lee VH, Law AL, Pang HH, Lam K, Lau V, Cui TY, Fong AS, Lee SW, Wong EC, Dai JW, Chan AC, Cheung T, Fung JY, Yeung RM, Luk M, Leung T, Lo C. Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant. Hepatology 2021; 74:2580-2594. [PMID: 34091914 PMCID: PMC9291538 DOI: 10.1002/hep.31992] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 05/26/2021] [Accepted: 05/30/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence-free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha-fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. CONCLUSIONS SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.
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Affiliation(s)
- Tiffany Cho‐Lam Wong
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - Victor Ho‐Fun Lee
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - Ada Lai‐Yau Law
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Herbert H. Pang
- School of Public HealthThe University of Hong KongHong Kong S.A.R.
| | - Ka‐On Lam
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - Vince Lau
- Department of RadiologyQueen Mary HospitalHong Kong S.A.R.
| | | | | | - Sarah Wai‐Man Lee
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Edwin Chun‐Yin Wong
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Jeff Wing‐Chiu Dai
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - Albert Chi‐Yan Chan
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - Tan‐To Cheung
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - James Yan‐Yue Fung
- Department of MedicineThe University of Hong KongHong Kong S.A.R.,Department of MedicineQueen Mary HospitalHong Kong S.A.R.
| | - Rebecca Mei‐Wan Yeung
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Mai‐Yee Luk
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - To‐Wai Leung
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - Chung‐Mau Lo
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
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Subramanian V, Chapman W. Living Donor Liver Transplant for Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1594-1595. [PMID: 30937661 DOI: 10.1245/s10434-019-07206-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Indexed: 09/07/2023]
Affiliation(s)
- Vijay Subramanian
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA
| | - William Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA.
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Ma KW, She WH, Chan ACY, Cheung TT, Fung JYY, Dai WC, Lo CM, Chok KSH. Validated model for prediction of recurrent hepatocellular carcinoma after liver transplantation in Asian population. World J Gastrointest Oncol 2019; 11:322-334. [PMID: 31040897 PMCID: PMC6475674 DOI: 10.4251/wjgo.v11.i4.322] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/03/2019] [Accepted: 01/08/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Liver transplantation (LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma (HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive agents. AIM To develop a scoring system to predict HCC recurrence after LT in an Asian population. METHODS Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a 60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic curve. RESULTS In total, 330 patients were eligible for analysis (183 in training and 147 in validation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were 78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [P = 0.012, hazard ratio (HR) 2.92], sum of maximum tumor size and number (P = 0.013, HR 1.15), and salvage LT (P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power (c-stat 0.748 and 0.85, respectively, in the training and validation sets). With the derived scores, patients were classified into low- (0-9), moderate- (> 9-14), and high-risk groups (> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54% (c-stat 0.67) and 4%, 22%, 62% (c-stat 0.811), accordingly. The risk stratification model was validated with chi-squared goodness-of-fit test (P = 0.425). CONCLUSION A validated predictive model featuring alpha-fetoprotein, salvage LT, and the sum of largest tumor diameter and total number of tumor nodule provides simple and reliable guidance for individualizing postoperative surveillance strategy.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, the University of Hong Kong, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, the University of Hong Kong, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - James Yan Yue Fung
- Department of Medicine and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, the University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
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Ma KW, Chok KSH, Fung JYY, Lo CM. Liver Transplantation for Hepatitis B Virus-related Hepatocellular Carcinoma in Hong Kong. J Clin Transl Hepatol 2018; 6:283-288. [PMID: 30271740 PMCID: PMC6160307 DOI: 10.14218/jcth.2017.00058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 01/09/2018] [Accepted: 01/31/2018] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. Curative resection is frequently limited in Hong Kong by hepatitis B virus-related cirrhosis, and liver transplantation is the treatment of choice. Liver transplantation has been shown to produce superior oncological benefits, when compared to hepatectomy for HCC. New developments in the context of patient selection criteria, modification of organ allocation, bridging therapy, salvage liver transplantation and pharmaceutical breakthrough have improved the survival of HCC patients. In this article, we will share our experience in transplanting hepatitis B virus-related HCC patients in Hong Kong and discuss the recent progress in several areas of liver transplantation.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - James Yan Yue Fung
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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Ma KW, Chok KSH, She WH, Chan ACY, Cheung TT, Dai WC, Fung JYY, Lo CM. Defining Optimal Surgical Treatment for Recurrent Hepatocellular Carcinoma: A Propensity Score Matched Analysis. Liver Transpl 2018; 24:1062-1069. [PMID: 29451360 DOI: 10.1002/lt.25033] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 08/22/2016] [Accepted: 10/31/2016] [Indexed: 12/27/2022]
Abstract
Salvage liver transplantation (sLT) and repeated resection (RR) are effective treatments for recurrent hepatocellular carcinoma (HCC), and comparisons of the oncological outcomes between these 2 modalities were scarce. Consecutive patients admitted for either sLT or RR for recurrent HCC were recruited. All patients in the present series received either prior hepatectomy, ablative therapy, or both before RR or sLT. Patient demographic, perioperative, and outcome data were analyzed. A survival analysis was performed after propensity score matching. There were 277 eligible patients recruited, and 67 and 210 of them underwent sLT and RR, respectively. Significant differences in preoperative hemoglobin, albumin, Model of End-Stage Liver Disease (MELD) score, and tumor number were found between the sLT and RR groups. After 1:3 propensity score matching, there were 36 sLT and 108 RR patients for comparison. The median age, MELD, alpha fetoprotein, and tumor size and number of the matched population were 57 years, 7.5, 16 ng/mL, 2.5 cm, and 1, respectively. There was no difference in the hospital mortality and complication rate (Clavien IIIa or above) between the groups. The recurrence rate after RR was significantly higher than for the patients who received sLT (72.2% versus 27.8%; P < 0.001). Following RR, 3 patients received liver transplantation for further recurrence, and 54.6% of the patients developed nontransplantable recurrence. The 5-year disease-free survival (DFS) and overall survival (OS) were both superior in the sLT group (DFS, 71.6% versus 32.8%, P < 0.001; OS, 72.8% versus 48.3%, P = 0.007). In conclusion, sLT is superior to RR for treatment of recurrent HCC in terms of DFS and OS. The high rate of nontransplantable recurrence after reresection underscores the importance of timely sLT.
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Affiliation(s)
- Ka Wing Ma
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Wong Hoi She
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Albert Chi Yan Chan
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Tan To Cheung
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Wing Chiu Dai
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - James Yan Yue Fung
- Division of Gastroenterology and Hepatology, Department of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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She WH, Chan ACY, Cheung TT, Lo CM, Chok KSH. Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels. World J Hepatol 2018; 10:308-318. [PMID: 29527266 PMCID: PMC5838449 DOI: 10.4254/wjh.v10.i2.308] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 12/18/2017] [Accepted: 02/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the impact of alpha-fetoprotein (AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival. METHODS Data of adult patients who received liver transplant (LT) for hepatocellular carcinoma (HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value < 10 ng/mL, high AFP level was defined as AFP value ≥ 10 to < 400 ng/mL, and very high AFP level was defined as AFP ≥ 400 ng/mL. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median (interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of < 0.05. RESULTS Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceased-donor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP < 10 ng/mL (n = 83); Group B, AFP ≥ 10 to < 400 ng/mL (n = 131); Group C, AFP ≥ 400 ng/mL (n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar (median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer (median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality (P = 0.626) and postoperative complication (P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger (A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria (P = 0.010). Poor differentiation and vascular permeation were also more common in this group (P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival (A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/mL for AFP (C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/mL was shown to affect the overall survival of the patients. CONCLUSION HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/mL was associated with disease recurrence, and AFP level of 105 ng/mL was found to be the cut-off value for overall survival difference.
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Affiliation(s)
- Wong Hoi She
- Department of Surgery, University of Hong Kong, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery and State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery and State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery and State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
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Ma KW, Cheung TT. When to consider liver transplantation in hepatocellular carcinoma patients? Hepat Oncol 2017; 4:15-24. [PMID: 30191050 PMCID: PMC6095144 DOI: 10.2217/hep-2016-0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 04/06/2017] [Indexed: 12/12/2022] Open
Abstract
Orthotopic liver transplantation (LT) has been regarded as the best cure among the three curative treatment modalities. However, when to consider LT in hepatocellular carcinoma (HCC) patients remains a complicated clinical question. In this article, we will look into the recent updates in the context of LT for HCC, including the timing of orthotopic LT (primary or salvage LT), patient selection criteria, newer prognostic markers and scoring systems, down-staging and bridging therapy, salvage LT and treatment option of post-LT HCC recurrence. Evolution of immunosuppressive therapy and future development of the LT for HCC will also be discussed.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, Queen Mary Hospital, the University of Hong Kong, Hong Kong
| | - Tan To Cheung
- Department of Surgery, Queen Mary Hospital, the University of Hong Kong, Hong Kong
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Chan SC, Cheung TT, Chan ACY, Chok KSH, Sharr WW, Fung JYY, Liu CL, Fan ST, Lo CM. New insights after the first 1000 liver transplantations at The University of Hong Kong. Asian J Surg 2016; 39:202-210. [PMID: 26143970 DOI: 10.1016/j.asjsur.2015.03.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 03/09/2015] [Accepted: 03/10/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/OBJECTIVE One thousand liver transplantations have been performed at the only liver transplant center in Hong Kong over a period of 22 years, which covered the formative period of living donor liver transplantation. These 1000 transplantations, which marked the journey of liver transplantation from development to maturation at the center, should be educational. This research was to study the experience and to reflect on the importance of technical innovations and case selection. METHODS The first 1000 liver transplantations were studied. Key technical innovations and surgical therapeutics were described. Recipient survival including hospital mortality was analyzed. Recipient survival comparison was made for deceased donor liver transplantation and living donor liver transplantation indicated by hepatocellular carcinoma and other diseases. RESULTS Among the 1000 transplantations, 418 used deceased donor grafts and 582 used living donor grafts. With the accumulation of experience, hospital mortality improved to < 2% in the past 2 years. In the treatment of diseases other than hepatocellular carcinoma, living donor liver transplantation was superior to deceased donor liver transplantation, with a 10-year recipient survival around 90%. CONCLUSION Transplant outcomes have been improving consistently over the series, with a very low hospital mortality and a predictably high long-term survival.
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Affiliation(s)
- See Ching Chan
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
| | - Tan To Cheung
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Albert C Y Chan
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Kenneth S H Chok
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - William W Sharr
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - James Y Y Fung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Chi Leung Liu
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Sheung Tat Fan
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
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11
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She WH, Cheung TT. Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation. Transl Gastroenterol Hepatol 2016; 1:34. [PMID: 28138601 DOI: 10.21037/tgh.2016.03.04] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 01/04/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common primary malignancy worldwide especially in the patients with the background of chronic liver disease. Liver transplantation (LT) is the only curative treatment effective for both malignancy as well as the cirrhosis and portal hypertension. Unfortunately, living donor is not always possible and the deceased graft is scarce. Neoadjuvant therapies, therefore, have been developed as a downstaging treatment to try to downstage the tumor within the transplant criteria, or as a bridging therapy to control the tumor growth in patients while waiting in the transplant list. This paper reviewed the common modalities used as bridging and downstaging therapies for patients suffering from HCC before undergoing LT.
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Affiliation(s)
- Wong Hoi She
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Tan To Cheung
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
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12
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Abstract
PURPOSE OF REVIEW To review and highlight recent literature regarding the medical management of adult patients undergoing liver transplantation. RECENT FINDINGS The addition of serum sodium concentration to the model for end-stage liver disease (MELD) score more accurately predicts 90-day waitlist mortality. Predictors of waitlist mortality and posttransplant survival include lower albumin and the presence of ascites, varices, and encephalopathy, as well as more nontraditional predictors such as older age, obesity, frailty, and sarcopenia. Indications for liver transplantation are evolving with the advent of effective therapy for hepatitis C and the increased prevalence of nonalcoholic steatohepatitis. Disparities persist in the current allocation system, including geographic variation and MELD inflation for hepatocellular carcinoma. Share 35 allows for broader regional sharing of organs for patients with the highest need, without detrimental effects on waitlist mortality or survival. Everolimus is a recently approved option for posttransplant immunosuppression that spares renal function. SUMMARY The MELD score has enabled the liver transplant community to equitably allocate organs. Recent literature has focused on the limitations of the MELD score and the disparities inherent in the current system. The next steps for liver transplantation will be to develop strategies to further optimize waitlist prioritization and organ allocation.
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Wan P, Zhang JJ, Li QG, Xu N, Zhang M, Chen XS, Han LZ, Xia Q. Living-donor or deceased-donor liver transplantation for hepatic carcinoma: A case-matched comparison. World J Gastroenterol 2014; 20:4393-4400. [PMID: 24764678 PMCID: PMC3989976 DOI: 10.3748/wjg.v20.i15.4393] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 12/20/2013] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma.
METHODS: From January 2007 to December 2010, 257 patients with pathologically confirmed hepatic carcinoma met the eligibility criteria of the study. Forty patients who underwent living-donor liver transplantation (LDLT) constituted the LDLT group, and deceased-donor liver transplantation (DDLT) was performed in 217 patients. Patients in the LDLT group were randomly matched (1:2) to patients who underwent DDLT using a multivariate case-matched method, so 40 patients in the LDLT group and 80 patients in the DDLT group were enrolled into the study. We compared the two groups in terms of clinicopathological characteristics, postoperative complications, long-term cumulative survival and relapse-free survival outcomes. The modified Clavien-Dindo classification system of surgical complications was used to evaluate the severity of perioperative complications. Furthermore, we determined the difference in the overall biliary complication rates in the perioperative and follow-up periods between the LDLT and DDLT groups.
RESULTS: The clinicopathological characteristics of the enrolled patients were comparable between the two groups. The duration of operation was significantly longer (553 min vs 445 min, P < 0.001) in the LDLT group than in the DDLT group. Estimated blood loss (1188 mL vs 1035 mL, P = 0.055) and the proportion of patients with intraoperative transfusion (60.0% vs 43.8%, P = 0.093) were slightly but not significantly greater in the LDLT group. In contrast to DDLT, LDLT was associated with a lower rate of perioperative grade II complications (45.0% vs 65.0%, P = 0.036) but a higher risk of overall biliary complications (27.5% vs 7.5%, P = 0.003). Nonetheless, 21 patients (52.5%) in the LDLT group and 46 patients (57.5%) in the DDLT group experienced perioperative complications, and overall perioperative complication rates were similar between the two groups (P = 0.603). No significant difference was observed in 5-year overall survival (74.1% vs 66.6%, P = 0.372) or relapse-free survival (72.9% vs 70.9%, P = 0.749) between the LDLT and DDLT groups.
CONCLUSION: Although biliary complications were more common in the LDLT group, this group did not show any inferiority in long-term overall survival or relapse-free survival compared with DDLT.
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