scholarly journals A94 RECURRENT HEPATOCELLULAR CARCINOMA: EVALUATION OF 8 POST-TRANSPLANT SCORING SYSTEMS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 110-110
Author(s):  
S Aziz ◽  
K Qumosani ◽  
A Teriaky
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Assessment ◽  
Liver Transplantation ◽  
Preliminary Data ◽  
Predictive Ability ◽  
Assessment Tools ◽  
Risk Scores ◽  
Term Survival ◽  
Post Transplant ◽  
Hcc Recurrence

Abstract Background Recurrence of hepatocellular carcinoma (HCC) after liver transplantation is a major cause of morbidity and mortality. It is well known that there is a discordance between pre-transplant imaging and post-transplant pathology that affect risk of recurrence. Several risk assessment tools have been developed, although to date, there is no widely accepted tool to predict HCC recurrence. Aims The aim of the current study is to determine which pathologic risk assessment score has the best predicative ability. Methods We retrospectively evaluated 152 patients over a twelve-year period that underwent liver transplantation for HCC. Using explanted pathology reports, each patient was stratified according to the pathologic risk score and followed over time for HCC recurrence. We evaluated eight pathologic risk scores and determined predictive ability by assessing the area under the receiver operating characteristic curve (AUROC). Results Out of 152 consecutive liver transplants for HCC, recurrence occurred in 21 patients (14%) with a mean follow-up of 59.5 months. 54% of patients were within Milan criteria prior to transplant. According to explant pathology, microvascular invasion was seen in 16% of patients, with majority of the tumors being moderately differentiated (48%), tumor size ≥ 3cm (52%), and 26% of tumors in both lobes of the liver. Preliminary data suggests that the Parfitt et. al score has the best predictive ability, with 60% of recurrence occurring in those considered high-risk. Further assessment via AUROC will be required to confirm the preliminary data. Conclusions Preliminary data suggests the Parfitt et al. score may have the best predictive ability to detect recurrence. This risk assessment tool can help tailor a surveillance strategy for early detection or early adjuvant therapy to improve long-term survival. Funding Agencies None

scholarly journals Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mamatha Bhat ◽  
Sergi Clotet-Freixas ◽  
Cristina Baciu ◽  
Elisa Pasini ◽  
Ahmed Hammad ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Protein Expression ◽  
Univariate Analysis ◽  
Milan Criteria ◽  
Post Transplant ◽  
Gene And Protein Expression ◽  
Galectin 3 ◽  
Transcriptomic Signature ◽  
Hcc Recurrence

Abstract Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples. Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.

TLR9-1486C/T polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation

2019 ◽  
Vol 13 (12) ◽  
pp. 995-1004 ◽  
Author(s):  
Sara de la Fuente ◽  
María-Jesús Citores ◽  
José-Luis Lucena ◽  
Pablo Muñoz ◽  
Valentín Cuervas-Mons
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Real Time Pcr ◽  
Tumor Recurrence ◽  
Post Transplant ◽  
Explanted Liver ◽  
Increased Risk ◽  
Poorly Differentiated ◽  
Hepatocellular Carcinoma Recurrence ◽  
Hcc Recurrence

Aim: To determine whether TLR9 polymorphisms are associated with tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC). Patients & methods: All patients who underwent liver transplantation, and had viable HCC in the explanted liver were included. TLR9-1237C/T and -1486C/T polymorphisms were analyzed by real-time PCR and melting curves analysis. Results: 20 of 159 patients (12.6%) developed post-transplant HCC recurrence. Tumors exceeding Milan criteria, moderately-to-poorly differentiated tumors and microvascular invasion on explants, and pretransplant α-fetoprotein level (all p < 0.01) were associated with an increased risk, while TLR9-1486TT genotype was associated with a decreased risk of HCC recurrence (p = 0.03). Conclusion:  TLR9-1486C/T might help to preoperatively identify patients at low risk of post-transplant HCC recurrence.

scholarly journals Effect of Mycophenolate Mofetil Therapy on Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Population-Based Cohort Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1558
Author(s):  
Yung-Fong Tsai ◽  
Fu-Chao Liu ◽  
Chun-Yu Chen ◽  
Jr-Rung Lin ◽  
Huang-Ping Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Cohort Study ◽  
Mycophenolate Mofetil ◽  
Recurrence Rate ◽  
Population Based ◽  
Defined Daily Dose ◽  
Post Transplant ◽  
Daily Dose ◽  
Hcc Recurrence

Hepatocellular carcinoma (HCC) recurrence after liver transplantation is associated with immunosuppressants. However, the appropriate immunosuppressant for HCC recipients is still debated. Data for this nationwide population-based cohort study were extracted from the National Health Insurance Research Database of Taiwan. A total of 1250 liver transplant recipients (LTRs) with HCC were included. We analyzed the risk factors for post-transplant HCC recurrences. Cumulative defined daily dose (cDDD) represented the exposure duration and was calculated as the amount of dispensed defined daily dose (DDD) of mycophenolate mofetil (MMF). The dosage effects of MMF on HCC recurrence and liver graft complication rates were investigated. A total of 155 LTRs, having experienced post-transplant HCC recurrence, exhibited low survival probability at 1-, 3-, 5-, and 10-year observations. Our results demonstrated increased HCC recurrence rate after liver transplantation (p = 0.0316) following MMF administration; however, no significant increase was demonstrated following cyclosporine, tacrolimus, or sirolimus administration. Notably, our data demonstrated significantly increased HCC recurrence rate following MMF administration with cDDD >0.4893 compared with cDDD ≤0.4893 or no administration of MMF (p < 0.0001). MMF administration significantly increases the risk of HCC recurrence. Moreover, a MMF-minimizing strategy (cDDD ≤ 0.4893) is recommended for recurrence-free survival.

Phase I trial of sorafenib following liver transplantation in patients with high-risk hepatocellular carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 401-401
Author(s):  
Abby B. Siegel ◽  
Anthony B. El-Khoueiry ◽  
Richard S. Finn ◽  
Katherine Guthrie ◽  
Alan P. Venook ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
High Risk ◽  
Phase I ◽  
Phase I Trial ◽  
Recurrence Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Risk Of Recurrence ◽  
Post Transplant

401 Background: Liver transplantation (LT) offers excellent long-term survival for hepatocellular carcinoma (HCC) patients who are within established criteria. For those outside such criteria, or with high risk pathologic features in the explant, HCC recurrence rates after LT are high. No treatment has been shown to decrease risk of recurrence post-LT. We conducted a multicenter phase I trial of sorafenib in LT patients with high-risk HCC. Methods: Subjects had pathologically proven high-risk HCC defined as outside Milan (pre- or post-transplant), poorly differentiated tumors, or tumors with vascular invasion. We used a standard 3+3 phase I design, beginning drug between 4 and 16 weeks after LT, with planned duration of treatment of 24 weeks. Cohort dosages were: 1) 200 mg per day, 2) 200 mg twice a day, 3) 200 mg/400 mg per day 4) 400 mg BID. Correlative studies included circulating endothelial cells (CECs) and plasma biomarkers collected prior to treatment, at 1 month, and at recurrence in a subset of subjects, and tumor expression of p-Erk, p-Akt, and c-Met in tissue microarrays. Results: We enrolled 14 patients. Median age was 63 years, and 93% were men. 71% had underlying HCV and 21% had HBV. Maximum tolerated dose (MTD) was 200 mg BID; only 43% of patients received >80% of planned dose. Grade 3-4 toxicities seen in >10% of subjects included: leukopenia (29%), LFT abnormalities (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 953 days, 1 patient died and 4 recurred, with a median recurrence-free survival of 716 days for the 4 patients who recurred. Mean CEC number at baseline was 21 cells/4 ml for those who recurred, and 80 cells/4 ml for those who did not (p=0.10). Mean sVEGFR2 levels decreased after 1 month on sorafenib (p=0.09), but did not correlate with recurrence. There was a trend for tumor c-Met expression with increased risk of recurrence. Conclusions: Post-transplant sorafenib is feasible and tolerable at 200 mg PO BID. Recurrence-free survival appears longer than expected but needs further validation in a larger study. Clinical trial information: NCT00997022.

scholarly journals Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4882
Author(s):  
Filippo Pelizzaro ◽  
Martina Gambato ◽  
Enrico Gringeri ◽  
Alessandro Vitale ◽  
Umberto Cillo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Cost Effective ◽  
Immunosuppressive Drugs ◽  
Surveillance Strategy ◽  
Post Transplant ◽  
Systemic Treatments ◽  
Hcc Recurrence

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.

Immune Checkpoint Inhibitors in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Case Report and Literature Review

2020 ◽  
Vol 20 (9) ◽  
pp. 720-727
Author(s):  
Jianguo Qiu ◽  
Wei Tang ◽  
Chengyou Du
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Immune Checkpoint ◽  
Graft Rejection ◽  
Checkpoint Inhibitors ◽  
Liver Graft ◽  
Immune Checkpoints ◽  
Term Survival ◽  
Liver Preservation ◽  
Programmed Death

Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied. Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT. Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed. Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival. Conclusions: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.

scholarly journals The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3730
Author(s):  
Berend R. Beumer ◽  
Roeland F. de Wilde ◽  
Herold J. Metselaar ◽  
Robert A. de Man ◽  
Wojciech G. Polak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Resection ◽  
Early Stage ◽  
Disease Free Survival ◽  
Milan Criteria ◽  
Term Survival ◽  
Equal Distribution ◽  
Intention To Treat ◽  
Treat Analysis

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.

scholarly journals Tailored Prediction Model of Survival after Liver Transplantation for Hepatocellular Carcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2869
Author(s):  
Indah Jamtani ◽  
Kwang-Woong Lee ◽  
Yun-Hee Choi ◽  
Young-Rok Choi ◽  
Jeong-Moo Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Prediction Model ◽  
Risk Group ◽  
Significant Risk ◽  
Risk Scores ◽  
Accurate Information ◽  
Survival Prediction ◽  
Good Prediction ◽  
Recurrence Rates

This study aimed to create a tailored prediction model of hepatocellular carcinoma (HCC)-specific survival after transplantation based on pre-transplant parameters. Data collected from June 2006 to July 2018 were used as a derivation dataset and analyzed to create an HCC-specific survival prediction model by combining significant risk factors. Separate data were collected from January 2014 to June 2018 for validation. The prediction model was validated internally and externally. The data were divided into three groups based on risk scores derived from the hazard ratio. A combination of patient demographic, laboratory, radiological data, and tumor-specific characteristics that showed a good prediction of HCC-specific death at a specific time (t) were chosen. Internal and external validations with Uno’s C-index were 0.79 and 0.75 (95% confidence interval (CI) 0.65–0.86), respectively. The predicted survival after liver transplantation for HCC (SALT) at a time “t” was calculated using the formula: [1 − (HCC-specific death(t’))] × 100. The 5-year HCC-specific death and recurrence rates in the low-risk group were 2% and 5%; the intermediate-risk group was 12% and 14%, and in the high-risk group were 71% and 82%. Our HCC-specific survival predictor named “SALT calculator” could provide accurate information about expected survival tailored for patients undergoing transplantation for HCC.

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