Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria

Hepatology ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 2014-2028 ◽  
Author(s):  
Ani Kardashian ◽  
Sander S. Florman ◽  
Brandy Haydel ◽  
Richard M. Ruiz ◽  
Goran B. Klintmalm ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Milan Criteria ◽  
Multicenter Cohort ◽  
Transplantation Outcomes

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 Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

HPB ◽  
2015 ◽  
Vol 17 (2) ◽  
pp. 168-175 ◽  
Author(s):  
Andreas Andreou ◽  
Safak Gül ◽  
Andreas Pascher ◽  
Wenzel Schöning ◽  
Hussein Al‐Abadi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Milan Criteria ◽  
Tumour Biology

Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the Milan Criteria: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 152 (5) ◽  
pp. S1124
Author(s):  
Thapanakul Emyoo ◽  
Piyapon Utako ◽  
Noriyo Yamashiki ◽  
Thunyarat Anothaisintawee ◽  
Ammarin Thakkinstian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Liver Transplantation ◽  
Meta Analysis ◽  
Milan Criteria

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.

Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan Criteria After Downstaging: Is It Worth It?

2018 ◽  
Vol 50 (2) ◽  
pp. 591-594 ◽  
Author(s):  
P. Cascales-Campos ◽  
L.A. Martinez-Insfran ◽  
P. Ramirez ◽  
D. Ferreras ◽  
M.R. Gonzalez-Sanchez ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Milan Criteria
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