Liver Transplantation For Hepatocellular Cancer Research Articles

Association of Serum Levels and Immunohistochemical Labelling of Des-Gamma-Carboxy-Prothrombin in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular cancer (HCC) is one of the main reasons for liver transplantation (LT). Biomarkers, such as alpha-foetoprotein (AFP) and Des-gamma-carboxy-prothrombin (DCP), can be helpful in defining the recurrence risk post LT. This study aims to evaluate the association between the intensity of DCP immunohistochemical labelling and serum DCP levels in patients undergoing LT for HCC. We carried out a prospective monocentric study including patients who all underwent LT for cirrhosis between 2016 and 2018 and all fell under the Milan criteria. The accepted diagnostic criteria for HCC were contrast-enhanced imaging and histology. Thirty-nine patients were followed for a median of 21 months, with HCC lesions categorized into negative, focally positive, and diffusely positive groups based on DCP immunohistochemistry. The serum DCP levels were significantly higher in the positive groups (258 mAU/mL for the focally and 257 mAU/mL for the diffusely positive) than in the negative group (48 mAU/mL) (p = 0.005) at diagnosis and at the time of liver transplantation (220 mAU/mL for the diffuse positive group). Microvascular invasion (58.8% vs. 19.0% for the diffusely positive and negative groups, respectively, p < 0.001) and lesion size (20 mm in the diffusely labelled group versus 12 mm in the other groups, p = 0.002) were significantly correlated with DCP labelling. Late recurrence occurred only in the positive groups; in the negative group, it occurred within the first 3 months after transplantation. DCP labelling in liver lesions correlates with serum levels and a more aggressive tumour profile. Further investigation is needed to determine if highly DCP-labelled tumours allow for the better selection of high-risk patients before LT.

Predictive Value of Preoperative 18 Fludeoxyglucose Positron Emission Tomography–Computed Tomography for Survival in Liver Transplantation Due to Hepatocellular Cancer

We aimed to study the predictive value of preoperative perform [18F] Fludeoxyglucose positron emission tomography-computed tomography ([18] FDG PET-CT) for survival in liver transplantation due to hepatocellular cancer. Ninety-six patients who underwent liver transplantation for hepatocellular cancer (HCC) after preoperative PET-CT evaluation were examined for the study. All patients' ages, genders, body mass index, blood groups, Child-Pugh and Model for End-Stage Liver Disease scores, etiologies, median Alpha Fetoprotein values, Milan Criteria and T stages, grades, macrovascular and microvascular invasions, multicentricities, maximum and total tumor sizes, tumor number findings in explant specimens, and recurrence rates were analyzed statistically. Statistically, microvascular (P = .002) and macrovascular invasions (P = .034) were observed more frequently in patients who are PET-CT (+) compared with patients who are PET-CT (-). PET-CT positivity was associated with shortened disease-free survival (DFS) statistically (P = .004). Positron emission tomography-CT positivity may be important for predicting prognostic markers such as DFS and vascular invasion in the preoperative evaluation. Before transplantation, PET-CT should be applied to all patients with HCC.

Transarterial Chemoembolization in Therapy of Patients with Recurrence of Hepatocellular Cancer in a Liver Transplant: a Clinical Case

Resection and orthotopic liver transplantation are considered radical methods in patients with hepatocellular cancer (HCC). However, recurrence is observed in 6-20 % of patients who have undergone liver transplantation for hepatocellular cancer. In about 20 % of cases there is an local lesion of the transplant, and a combination of intra- and extrahepatic metastasis is observed in at least 30 % of patients. At the time of detection of the recurrence of HCC in the liver transplant, most patients are no longer subject to radical treatment due to the presence of multifocal bilobar liver damage or extrahepatic metastasis. Transarterial chemoembolization (TACE) can be a method of choice, can make it possible long-term local control of the tumor process in the liver transplant.

Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1years (14days-18.6years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.

Long-term results of liver transplantation for hepatocellular cancer

Aim. To study the long-term results of liver transplantation for hepatocellular carcinoma in accordance with various criteria for selecting patients for surgery. Materials and methods . The results of 71 liver transplantations for hepatocellular carcinoma have been studied. Long- term survival and disease-free survival have been studied in accordance with various criteria for selecting patients for liver transplantation. Results . The five-year survival rate was 84.3%, the median survival rate was 47.4 months. Higher overall survival and disease-free survival rates were found in patients after living donor liver transplantation compared to patients after cadaveric liver transplantation. The five-year survival rate for patients within the Milan criteria compared to those beyond the Milan criteria were 92.4% vs 74.1%. The five-year survival rate for patients within the UCSF criteria compared to patients beyond the UCSF criteria were 93.3% vs 68.3%. The five-year survival rate for patients within the Up-to-seven criteria compared to patients beyond the Up-to-seven criteria were 88.4% vs 71.0%. The five-year survival rate for patients within the Hangzhou criteria compared to patients beyond the Hangzhou criteria were 84.4% vs 72.9%. Hepatocellular carcinomas recurrent were in 8.4% of patients in the long-term period of liver transplantation. The five-year disease-free survival rate among all patients was 87.7%. The median disease-free survival rate was 43.2 months. The five-year disease-free survival rate for patients within criteria were from 85.4% (Hangzhou University) to 93.3% (UCSF). The five-year disease-free survival rate for patients beyond criteria were from 68.3% (UCSF) to 74.1% (Milan criteria). A statistically significant relapse rate was observed in patients with a Guerrini coefficient &gt;2.3, regardless of the selection criteria in all study groups of patients. Conclusion . The optimal prognostic criteria for liver transplantation for patients with hepatocellular carcinoma are the Milan criteria. Some expansion of the Milan criteria show comparable results. In this regard, it can be assumed that the optimal criteria have not been found at present, which requires new ways to search for expansion of the Milan criteria, taking into account the level of AFP, tumor differentiation, etc.

An imageomics and multi-network based deep learning model for risk assessment of liver transplantation for hepatocellular cancer.

Liver transplantation (LT) is an effective treatment for hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Patients with small HCC (<5 cm) are given priority over others for transplantation due to clinical allocation policies based on tumor size. Attempting to shift from the prevalent paradigm that successful transplantation and longer disease-free survival can only be achieved in patients with small HCC to expanding the transplantation option to patients with HCC of the highest tumor burden (>5 cm), we developed a convergent artificial intelligence (AI) model that combines transient clinical data with quantitative histologic and radiomic features for more objective risk assessment of liver transplantation for HCC patients. Patients who received a LT for HCC between 2008-2019 were eligible for inclusion in the analysis. All patients with post-LT recurrence were included, and those without recurrence were randomly selected for inclusion in the deep learning model. Pre- and post-transplant magnetic resonance imaging (MRI) scans and reports were compressed using CapsNet networks and natural language processing, respectively, as input for a multiple feature radial basis function network. We applied a histological image analysis algorithm to detect pathologic areas of interest from explant tissue of patients who recurred. The multilayer perceptron was designed as a feed-forward, supervised neural network topology, with the final assessment of recurrence risk. We used area under the curve (AUC) and F-1 score to assess the predictability of different network combinations. A total of 109 patients were included (87 in the training group, 22 in the testing group), of which 20 were positive for cancer recurrence. Seven models (AUC; F-1 score) were generated, including clinical features only (0.55; 0.52), magnetic resonance imaging (MRI) only (0.64; 0.61), pathological images only (0.64; 0.61), MRI plus pathology (0.68; 0.65), MRI plus clinical (0.78, 0.75), pathology plus clinical (0.77; 0.73), and a combination of clinical, MRI, and pathology features (0.87; 0.84). The final combined model showed 80 % recall and 89 % precision. The total accuracy of the implemented model was 82 %. We validated that the deep learning model combining clinical features and multi-scale histopathologic and radiomic image features can be used to discover risk factors for recurrence beyond tumor size and biomarker analysis. Such a predictive, convergent AI model has the potential to alter the LT allocation system for HCC patients and expand the transplantation treatment option to patients with HCC of the highest tumor burden.

Importance of Intraoperative Transfusions of Packed Red Blood Cells and Fresh Frozen Plasma in Liver Transplantation for Hepatocellular Cancer.

BackgroundThe impact of packed red blood cells (PRBCs) and fresh frozen plasma (FFP) transfusions in patients with hepatocellular cancer (HCC) undergoing liver transplantation has rarely been evaluated. The aim of the current study was to assess the impact of intraoperative transfusions on posttransplant outcomes.Material/MethodsThis retrospective cohort study was based on 229 HCC transplant recipients. The primary outcome measure was 5-year recurrence-free survival. Secondary outcome measures comprised overall and long-term survival at 5 years and 90-day mortality. Cox proportional hazard models and logistic regression were used to assess risk factors.ResultsAfter adjustment for potential confounders, no association was found with respect to tumor recurrence for PRBCs (P=0.368) or FFP (P=0.081) transfusions. Similarly, PRBC transfusion (P=0.623) and FFP transfusion (P=0.460) had no impact on survival between 90 days and 5 years. PRBC transfusion increased the risk of 90-day mortality (P=0.005), while FFP transfusion was associated with a lower risk (P=0.036).ConclusionsIntraoperative transfusions of blood products does not impair recurrence-free and long-term survival of patients with HCC undergoing liver transplantation. Intraoperative PRBC transfusion increases the risk of early mortality, whereas adequate supplementation of FFP plays a protective role.

Extended criteria for liver transplantation in hepatocellular carcinoma. A retrospective, multicentric validation study in Belgium

BackgroundRecent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC. Methods526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing. ResultsOverall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence. ConclusionsAll validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC.

Obtaining Optimal Long-Term Outcomes from Liver Transplantation for Hepatocellular Cancer.

Liver transplantation is the definitive treatment for patients with end-stage liver disease. Liver transplantation is also the optimal treatment for patients with hepatocellular carcinoma (HCC), especially in the setting of chronic liver disease. Unfortunately, due to the worldwide shortage of organs, this treatment is not available for all patients with HCC. Strict selection criteria have been developed in order to obtain optimal results. A surgical perspective of the preoperative selection, perioperative management, and postoperative care of patients is reviewed in depth and provides an overview for obtaining optimal long-term results from liver transplantation for HCC. With rigorous selection and patient management, excellent long-term outcomes can be obtained with liver transplantation for patients with HCC.

The Predictive Ability of the Glasgow Prognostic Score and Variants in Both Deceased Donor and Living Donor Liver Transplantation for Hepatocellular Cancer

AimLiver transplantation (LT) is the most promising treatment method in hepatocellular cancer (HCC). Due to the shortage of organ donors and the possible risks associated with living donation, the selection of patients for LT is critical. The aim of this study is to investigate the predictive ability of the Glasgow Prognostic Score (GPS), modified GPS (mGPS), and hepatic GPS (hGPS) on prognoses in a patient group who underwent deceased donor LT (DDLT) or living-donor LT (LDLT) for HCC. Patients and MethodsThis study includes 62 DDLT and 55 LDLT patients who underwent LT for HCC between 1998 and 2016 in a single center. The study endpoints were recurrence, 0- to 1-year mortality, 0- to 3-year mortality, mortality, and overall survival (OS). ResultsThe median follow-up time was 70.24 ± 48.47 months. GPS and hGPS positivity were found to be prognostic indicators of 0- to 3-year mortality and overall mortality in DDLT (P = .012, P = .006; P = .044 and P = .022 respectively). In the LDLT group, GPS was found to be effective in predicting 0- to 1-year and 0- to 3-year mortality (P = .045, P = .022 respectively); GPS and hGPS were also found to be effective in predicting overall mortality (P = .001 and P = .046 respectively). The OS was significantly longer in the GPS 0 group and hGPS 0 group compared to the GPS 1-2 and hGPS 1-2 group in both DDLT and LDLT. ConclusionThe findings of this study and the literature indicate that using GPS and hGPS is appropriate in selecting patients with HCC who are candidates for LT.

Variables impacting on the outcomes after liver transplantation for hepatocellular cancer within UCSF criteria

Variables impacting on the outcomes after liver transplantation for hepatocellular cancer within UCSF criteria

Addition of alfa fetoprotein to traditional criteria for hepatocellular carcinoma improves selection accuracy in liver transplantation

Objectives: Liver transplantation in hepatocellular cancer (HCC) is curative only for a selection of patients. Commonly used criteria are mostly based on tumor size and number. However, patients within criteria do have tumor recurrences after transplantation and patients outside criteria are excluded even though some could benefit from transplantation. The tumor marker alpha fetoprotein (AFP) is associated with poor outcome and has already been reported to improve selection. We investigated the hypothesis that AFP level combined with traditional selection criteria could ameliorate the selection accuracy for liver transplantation in HCC.Materials and methods: A retrospective national cohort study in 336 patients who had liver transplantation for HCC in Sweden 1996–2014.Results: AFP cut-off levels of 20, 100, 1000 and >1000 ng/mL stratified both survival and tumor recurrence, with estimated 5-year survival rates of 74, 61, 49 and 31%, respectively. A simple score, combining three risk levels according to Milan and UCSF fulfillment with three levels of AFP, increased predictive accuracy. A high score identified 35 at-risk patients with estimated post-transplant 5-year survival rate of only 29% compared to 50% for 76 patients excluded by UCSF. More patients were within the combined score cut-off compared to within UCSF, but 5-year survival was similar, 67% versus 66%.Conclusion: AFP combined with traditional selection criteria ameliorates the selection accuracy for liver transplantation in HCC.

Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: A systematic review and meta-analysis.

AIMTo perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio (PLR) as a risk factor for post-transplant hepatocellular cancer (HCC) recurrence.METHODSA systematic literature search was performed using PubMed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria: (1) studies comparing pre-transplant low vs high PLR values; (2) studies reporting post-transplant recurrence rates; and (3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation.RESULTSA total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases (80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation (OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I2 statistic value.CONCLUSIONPre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results.

Liver transplantation for hepatocellular carcinoma: pre-transplant considerations and post-transplant management

Hepatocellular cancer is the seventh most frequent and third leading cause of cancer death worldwide. At its early stages, it could be amenable to complete cure using surgical resection or ablative therapies. Unfortunately, some patients present with advanced tumor stages or have reduced liver function and locoregional therapies may not be used or effective. Liver transplantation becomes an appealing option as it replaces the ailing liver and offers a chance for complete cure. Outcomes of liver transplantation for hepatocellular cancer have improved with better patient selection and adjuvant therapies allow patients to become eligible for transplantation and minimize dropouts from the waiting list. Post-transplant care, including appropriate surveillance and immunosuppression can also improve long-term outcomes with survival similar to transplantation for non-oncologic indications.

The pretransplant neutrophil-lymphocyte ratio as a new prognostic predictor after liver transplantation for hepatocellular cancer: a systematic review and meta-analysis.

Recently, many reports showed that the pretransplant neutrophil-lymphocyte ratio (NLR) may be correlated with the prognosis of patients undergoing liver transplantation (LT) for hepatocellular cancer (HCC). However, their results still remained controversial. Thus we performed a meta-analysis of 13 studies to estimate the prognostic value of pretransplant NLR. Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to September2017. Hazard ratio (HR) or odds ratio (OR) with its 95%CI was used to evaluate the association between elevated NLR and the prognosis or clinical features of liver cancer patients. A total of 13 studies including 1936 patients were included in this meta-analysis. Elevated pretransplant NLR had a close association with the overall survival (HR: 2.22; 95% CI: 1.34-3.68), recurrence-free survival (HR: 3.77; 95% CI: 2.01-7.06) and disease-free survival(HR: 2.51; 95% CI: 1.22-5.15) of patients undergoing LT for HCC, respectively. In addition, elevated NLR was associated with the presence of vascular invasion (OR: 2.39; 95% CI: 1.20-4.77) and Milan criteria (OR: 0.26; 95% CI: 0.17-0.40). The results of this meta-analysis showed that elevated pretransplant NLR may be used as a new prognostic predictor after LT for HCC.

Hepatocellular cancer and recurrence after liver transplantation: what about the impact of immunosuppression?

Liver transplantation (LT) has originally been designed to treat hepatobiliary malignancies. The initial results of LT for hepatocellular cancer (HCC) were, however, dismal this mainly due to the poor patient selection procedure. Better surgical and perioperative care and, especially, the refinement of selection criteria led to a major improvement of results, making HCC nowadays (again!) one of the leading indications for LT. This evolution is clearly shown by the innumerable reports aiming to further extend inclusion criteria for LT in HCC patients. Nonetheless, the vast majority of papers only deals with morphologic (tumour diameter and number) and (only recently) biologic (tumour markers and response to locoregional treatment) parameters to do so. Curiously enough, the role of both the immune competent state of the recipient as well as the impact of both immunosuppression (IS) type and load has been very poorly addressed in this context, even if it has been shown for a long time, based on both basic and clinical research, that they all play a key role in the outcome of any oncologic treatment and in the development of de novo as well as recurrent tumours. This chapter aims to give, after a short introductive note about the currently used inclusion criteria of HCC patients for LT and about the role of IS in carcinogenesis, a comprehensive overview of the actual literature related to the impact of different immunosuppressive drugs and schemes on outcome of LT in HCC recipients. Unfortunately, up to now solid conclusions cannot be drawn due to the lack of high-level evidence studies caused by the heterogeneity of the studied patient cohorts and the lack of prospectively designed and randomized studies. Based on long-term personal experience with immunosuppressive handling in LT some proposals for further clinical research and practice are put forward. The strategy of curtailing and minimising IS should be explored in the growing field of transplant oncology taking thereby into account the immunological privilege of the liver allograft. These strategies will become more and more compelling when further extending the indications in which adjuvant chemotherapy will probably become an inherent part of the therapeutic scheme of HCC liver recipients.

The growing impact of alpha-fetoprotein in the field of liver transplantation for hepatocellular cancer: time for a revolution.

The role of alpha-fetoprotein (AFP) in the specific setting of the diagnosis and prognosis of patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still controversial. Recently, a marked interest for this marker has been reported, mainly related to its ability to predict the outcome of HCC patients after LT. The growing number of papers in PubMed indicates that AFP has begun a "second life" in the particular context of LT. Looking at the most recent International Guidelines on HCC, it looks obvious that time is ripe to reevaluate the value of AFP in relation to its prognostic ability to identify HCC patients at high-risk for drop-out before and recurrence after LT. Many discrepancies exist worldwide regarding the use of biomarkers in HCC. In contrast to the Western world, AFP is widely used in Asian countries, the reason why being unclear. Indeed, in the (merely Western-dominated) HCC treatment algorithms, the role of AFP as a prognostic tumor marker is still considered to be "under investigation". One should however realize that the underestimation of the value of AFP in the LT context will hamper further refinements of both the liver allograft allocation process and the selection of the best candidates for this procedure. Moreover, AFP has an important role to play in the monitoring of bridging and/or downstaging procedures bringing eventually the patient to transplantation. So, time has come to reconsider the role and value of AFP (dynamics) in the field of transplant oncology.

Living donor liver transplantation for hepatocellular cancer: an (almost) exclusive Eastern procedure?

Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and it is linked with chronic liver disease. Liver transplantation (LT) is the best curative treatment modality, since it can cure simultaneously the underlying liver disease and HCC. Milan criteria (MC) are the benchmark for selecting patients with HCC for LT, achieving up to 91% 1-year survival post transplantation. However, when considering intention-to-treat (ITT) rates are substantially lower, mainly due dropout. Additionally, Milan criteria (MC) are too restrictive and more inclusive criteria have been reported with good outcomes. Mainly, in Eastern countries, deceased donors are scarce, therefore Asian centers have developed living-donor liver transplantation (LDLT) to a state-of-art status. There are many eastern centers reporting huge numbers of LDLT with outstanding results. Regarding HCC patients, they have reported many criteria including more advanced tumors achieving reasonable outcomes. Western countries have well-established deceased-donor liver transplantation (DDLT) programs. However, organ shortage and restrictive criteria for listing patients with HCC endorses LDLT as a good option to offer curative treatment to more HCC patients. However, there are some controversial reports claiming higher rates of HCC recurrence after LDLT than DDLT. An extensive review included 30 studies with cohorts of HCC patients who underwent LDLT in both East and West countries. We reported also the results of our Institution, in Brazil, where it was performed the first LDLT. This review also addresses the eligibility criteria for transplanting patients with HCC developed in Western and Eastern countries.

Challenging the principle of utility as a barrier for wider use of liver transplantation for hepatocellular cancer

BackgroundAlthough transplant benefit appears superior for patients with advanced hepatocellular cancer (HCC), liver transplantation remains limited to selected low-risk HCC patients to keep their outcomes similar to heterogeneous group of non-HCC patients. The purpose of this study was to assess the rationale for current policy of restricting access to liver transplantation to minority of HCC patients based on utility principle.MethodsThis retrospective cohort study comprised 1246 liver transplant recipients, including 206 HCC and 1040 non-HCC patients. Patient survival was the primary outcome measure. Patients with HCC and benign diseases were divided into low-, moderate-, and high-risk subgroups basing on independent risk factors for disease-free survival and model for end-stage liver disease (MELD) score (<30, 30–40, >40), respectively.ResultsMELD (p < 0.001) and presence of HCC (p = 0.008) were independent risk factors for early and late mortality, respectively. Total tumor volume (p = 0.008) and alpha-fetoprotein (p = 0.013) were independent predictors of recurrence and mortality used for division of HCC patients into low-, moderate-, and high-risk subgroups, with disease-free survival rates of 74.9% (5 years), 51.7% (5 years), and 8.0% (3 years), respectively (p < 0.001). There were no differences in 5-year overall survival between low-risk HCC (74.9%) and non-HCC (81.9%) patients (p = 0.210), moderate-risk HCC (63.3%) and non-HCC (68.0%) patients (p = 0.372), and high-risk HCC (55.0%) and non-HCC (56.0%) patients (p = 0.559).ConclusionsThe principle of utility is unequally applied for restriction of access to liver transplantation for HCC patients. The results provide rationale for discussion on reinitiation of liver transplantation for advanced HCCs.

The Warsaw Proposal for the Use of Extended Selection Criteria in Liver Transplantation for Hepatocellular Cancer

BackgroundCombination of the University of California, San Francisco (UCSF) and the up-to-7 criteria with alpha-fetoprotein (AFP) cutoff of 100 ng/ml was proposed as the Warsaw expansion of the Milan criteria in selection of hepatocellular cancer (HCC) patients for liver transplantation. The purpose of this retrospective study was to validate this proposal.MethodsA total of 240 HCC patients after liver transplantation were included. Recurrence-free survival and overall survival at 5 years were set as the primary and secondary outcome measures, respectively.ResultsThe Warsaw expansion increased transplant eligibility rate by 20.3 %. AFP >100 ng/ml significantly increased the recurrence risk in patients within the Milan criteria (p = 0.025) and in those beyond, yet within either the UCSF or the up-to-7 criteria (p < 0.001). Recurrence-free survival at 5 years was 90.8 % for patients within the Milan criteria, 100.0 % in patients within the Warsaw expansion, 54.9 % in patients beyond the Warsaw expansion but within either the UCSF or the up-to-7 criteria, and 45.1 % in patients beyond both the UCSF and the up-to-7 criteria (p < 0.001). The corresponding overall survival rates were 71.6, 82.4, 64.3, and 55.3 %, respectively (p = 0.027).ConclusionsThe Warsaw expansion of the Milan criteria substantially increases the recipient pool without compromising outcomes.