Hepatocellular Carcinoma Recipients Research Articles

Advances in predicting the prognosis of hepatocellular carcinoma recipients after liver transplantation.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Liver transplantation (LT) is known as a curative and therapeutic modality. However, the survival rates of recipients after LT are still not good enough because of tumor recurrence. To improve the survival rates of recipients after LT, identifying predictive factors for prognosis after LT and establishing a model assessing prognosis are very important to HCC patients. There has recently been a lot of clinical and basic research on recurrence and prognosis after LT. Progress has been made, especially in selection criteria for LT recipients and risk factors for predicting prognosis after LT. Hangzhou criteria, in line with China's high current incidence rate of primary liver, are first proposed by Chinese scholars of LT, and are accepted world-wide, and make an important contribution to the development of LT.

Time-Dependent Impact of Hepatocellular Carcinoma on Mortality after Liver Transplantation: A National Cohort Study

Background: Patients who receive a liver transplant for hepatocellular carcinoma (HCC) are in better physical condition than other liver transplant recipients. However, HCC patients often receive poorer quality livers. Tumour recurrence also has a negative effect on post-transplant outcomes. We compared mortality of HCC and non-HCC recipients in different post-transplant time periods ('epochs') to separate the impact of these different risk factors on short and longer term post-transplant survival. Methods: We identified a population-based cohort of first-time liver transplant recipients (aged = 16 years) between 2008 and 2016 in the UK. We used Cox regression to estimate hazard ratios (HR) comparing post-transplant mortality between HCC and non-HCC patients in three post-transplant epochs: 0 to 90 days, 90 days to 2 years, and 2 to 5 years, with adjustment first for recipient and later also for donor characteristics. Findings: 1 270 HCC and 3 657 non-HCC transplant recipients were included. 5-year post-transplant survival was 74.5% (95%CI 71.2% to 77.5%) in HCC patients and 84.6% (83.0% to 86.1%) in non-HCC patients. With adjustment for recipient characteristics only, mortality was lower but not statistically significantly different in the first 90-days (HR 0.76, 95% CI 0.53-1.09, p=0.11), but HCC recipients had significantly higher 90-day mortality (90 days to 2 years: 1.99, 1.48-2.66, P<0.001; 2 to 5 years 1.77, 1.30-2.42, p<0.001). Further adjustment for donor characteristics had little impact on these results. Interpretation: HCC recipients have poorer 5-year post-transplant survival than non-HCC recipients, most likely because of tumour recurrence. The more frequent use of poorer quality donor organs for HCC does not explain this difference which support the use of poorer quality donor organs for HCC recipients. Funding Statement: National Institute of Health Research. Declaration of Interests: JvdM reports grants from Healthcare Quality Improvement Partnership during the conduct of the study. All other authors declare no competing interests.

The Impact of Liver Graft Injury on Cancer Recurrence Posttransplantation.

Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 15-20%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs' doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of patient and graft loss. The recent identification of non-invasive "bio-markers of tolerance", which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients.

Expression and genetic polymorphism of necroptosis related protein RIPK1 is correlated with severe hepatic ischemia-reperfusion injury and prognosis after hepatectomy in hepatocellular carcinoma patients.

The goal of our study was to assess the prognostic impact of the necroptosis relative protein RIPK1 geneticpolymorphism in ischemia-reperfusion injury and survival after hepatectomy in hepatocellular carcinoma (HCC) patients. In this study, expression of RIPK1 and its genetic polymorphism(rs2272990) were examined in plasma of 44 HCC patients. All these patients were undergoing partial hepatectomy. The prognostic values of RIPK1 genetic polymorphism for tumor development and survival, and ischemia-reperfusion injury after hepatectomy were further determined. Plasma RIPK1 expressions were significantly increased in HCC patients, compared to the healthy control group. Totally 19 patients have the GA + AA genotype in the RIPK1 rs2272990 SNP site and 25 have GG genotype. There were no statistically significant intergroup differences observed in age, gender, AFP value, HBV positive, tumor size or cirrhosis. GG genotype had positive correlation with TNM classification (p= 0.033) and lymphatic metastasis (p= 0.027) and was significantly associated with severe hepatic ischemia-reperfusion injury and decreased survival rate after hepatectomy. In conclusion, the RIPK1 polymorphism is an indicator of hepatic injury and a novel prognostic biomarker for tumor development and survival of HCC recipients after hepatectomy.

GSTA2 Promotes Liver Tumor Recurrence after Liver Transplantation through Regulating ROS Metabolism

Introduction: Tumor recurrence remains a major obstacle in hepatocellular carcinoma (HCC) recipients after liver transplantation. Our previous studies have indicated that elevated hepatic injury at early-phase after liver transplantation promotes late-phase tumor progression and invasion[1][2]. GSTA2 was identified to be significantly upregulated in early-phase of HCC recipients who developed with tumor recurrence in late-phase. We aimed to investigate the prognostic value of circulating GSTA2 in predicting tumor recurrence after liver transplantation and explore its underlying molecular mechanism. Methods: Post-transplantation plasma GSTA2 protein of 70 HCC recipients was examined by ELISA analysis. The prognostic value of plasma GSTA2 in predicting tumor recurrence and survival was examined by statistical analyses. The expression level of GSTA2 and ROS-associated genes was examined by real-time RT-PCR. Suppression of GSTA2 in HCC cell lines was established by lentiviral approach. The roles of GSTA2 in regulating HCC proliferation, metastasis and ROS metabolism were studied by in vitro and in vivo functional assays. The effect of GSTA2 in regulating other ROS-associated genes was studied by by RT2 Profiler PCR array. Results: Higher level of plasma GSTA2 at early-phase after liver transplantation significantly predicted tumor recurrence of HCC recipients (Sensitivity = 0.875; specificity = 0.481; P = 0.031) (Fig.1A). Higher level of plasma GSTA2 was also significantly associated with poor overall (P = 0.041) and disease-free survival (P = 0.024) of HCC recipients (Fig. 1B and 1C). The expression level of hepatic GSTA2 after liver transplantation was significantly correlated with ROS-associated genes such as GPX2 and SOD3. Suppression of GSTA2 in HCC cells significantly inhibited in vitro and in vivo proliferation and metastasis of HCC cells. Upregulation of GSTA2 could compensate H2O2-induced high ROS stress and damage in both normal liver and HCC cells. Alteration of GSTA2 expression in HCC cells could influence the expression level of several ROS-associated genes such as NCF1, SOD3, MT3, MBL2, ALB, TPO and GPX5. Conclusion: Post-transplantation circulating GSTA2 is a potential biomarker for predicting tumor recurrence and survival of HCC recipients after liver transplantation. Higher level of GSTA2 after liver transplantation could promote tumor recurrence through regulating ROS metabolism.

A national report from China Liver Transplant Registry: steroid avoidance after liver transplantation for hepatocellular carcinoma.

We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation (LT) for hepatocellular carcinoma (HCC). We retrospectively analyzed HCC recipients without steroids after LT (SF group, n=368) based on the China Liver Transplant Registry (CLTR) database. These recipients were matched 1:2 with patients using steroids (S group, n=736) for the same period after LT for HCC, according to propensity scores. Multivariate analysis indicates that recipients with younger age [odds ratio (OR), 1.053; P=0.011], preoperative hepatitis B virus (HBV) DNA ≥1,000 copies/mL (OR, 2.597; P=0.004) and beyond Milan criteria (OR, 4.255; P<0.001) were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT. The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group (P<0.05). Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival (OR, 1.690; P<0.001) and tumor-free survival (OR, 2.066; P<0.001). The incidences of new-onset diabetes mellitus (21.20%vs. 33.29%, P<0.001), new-onset hypertension (10.05%vs. 18.61%, P<0.001) and hyperlipidemia (4.08%vs. 7.20%, P=0.042) were significantly lower in the SF group. Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT. Age, HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients. Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.

Poster

Poster

Early-phase circulating miRNAs predict tumor recurrence and survival of hepatocellular carcinoma patients after liver transplantation.

Post-liver transplantation tumor recurrence is a major challenge for hepatocellular carcinoma (HCC) recipients. We aimed to identify early-phase circulating microRNAs after liver transplantation for predicting tumor recurrence and survival of HCC recipients. Circulating microRNA profiles at early-phase (2-hour after portal vein reperfusion) after liver transplantation were compared between HCC recipients with (n=4) and without tumor recurrence (n=8) by microarray analyses. Candidate microRNAs were validated in 62 HCC recipients by quantitative RT-PCR. The prognostic values of microRNAs for tumor recurrence and survival were examined. Simulated in vitro ischemia-reperfusion injury models were employed to characterize the possible mechanism of up-regulation of circulating microRNAs. Our results showed that up-regulation of circulating miR-148a, miR-1246 or miR-1290 at early-phase was significantly associated with HCC recurrence after liver transplantation. Among them, miR-148a (p=0.030) and miR-1246 (p=0.009) were significant predictors of HCC recurrence. MiR-1246 was an independent predictor of overall (p=0.023) and disease-free survival (p=0.020) of HCC recipients. The level of early-phase circulating miR-1246 was positively correlated with serum AST and ALT levels in HCC recipients after liver transplantation. The expression of hepatic miR-1246 was positively correlated with TNFα mRNA. In vitro experiments indicated that injury-induced activation and differentiation of macrophages significantly elevated the expression and secretion of miR-1246. In conclusion, early-phase circulating miR-1246 is an indicator of hepatic injury and a novel prognostic biomarker for tumor recurrence and survival of HCC recipients after liver transplantation.

Validation of a criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation.

The aim of this study was to validate a criteria-specific long-term survival prediction model (MHCAT) in a large cohort of hepatocellular carcinoma (HCC) patients after liver transplantation (LT) in China. Independent risk factors in MHCAT were retrospectively analysed for HCC patients recorded in the China Liver Transplant Registry. Survival predictions for each patient were calculated using MHCAT scores and the Metroticket formula separately, and the prediction efficacy of MHCAT and Metroticket was compared using the area under ROC curve (c-statistic). A total of 1371 LTs for HCC were analysed in the study, with a median follow-up of 22.2 months (IQR 6.1–72.4 months). The proportions meeting the Milan, UCSF, Fudan and Hangzhou criteria were 34.4%, 39.7%, 44.2% and 51.9%, respectively. The c-statistics for MHCAT predictions of 3- and 5-year survival rates of HCC recipients were 0.712–0.727 and 0.726–0.741, respectively. Among these patients, 1298 LTs for HCC were ultimately selected for the comparison analysis for prediction efficacy. The c-statistic of MHCAT for predictions of 3-year survival with reference to the Milan, UCSF and Fudan criteria was significantly increased compared with that for Metroticket (p < 0.05). In conclusion, MHCAT can effectively predict long-term survival for HCC recipients after LT.

A score model for predicting post-liver transplantation survival in HBV cirrhosis-related hepatocellular carcinoma recipients: a single center 5-year experience

The prognostic prediction of liver transplantation (LT) guides the donor organ allocation. However, there is currently no satisfactory model to predict the recipients' outcome, especially for the patients with HBV cirrhosis-related hepatocellular carcinoma (HCC). The present study was to develop a quantitative assessment model for predicting the post-LT survival in HBV-related HCC patients. Two hundred and thirty-eight LT recipients at the Liver Transplant Center, First Affiliated Hospital, Zhejiang University School of Medicine between 2008 and 2013 were included in this study. Their post-LT prognosis was recorded and multiple risk factors were analyzed using univariate and multivariate analyses in Cox regression. The score model was as follows: 0.114X(Child-Pugh score)-0.002X(positive HBV DNA detection time)+0.647X(number of tumor nodules)+0.055X(max diameter of tumor nodules)+0.231XlnAFP+0.437X(tumor differentiation grade). The receiver operating characteristic curve analysis showed that the area under the curve of the scoring model for predicting the post-LT survival was 0.887. The cut-off value was 1.27, which was associated with a sensitivity of 72.5% and a specificity of 90.7%, respectively. The quantitative score model for predicting post-LT survival proved to be sensitive and specific.

The Race to Liver Transplantation: A Comparison of Patients With and Without Hepatocellular Carcinoma from Listing to Post-Transplantation

There are geographic and disease-specific inequities in liver allograft distribution. We examined differences between hepatocellular carcinoma (HCC) and non-HCC liver transplantation (LT) candidates from listing through LT in a region with prolonged wait times. We performed a single-center retrospective study, from 2005 to 2013, of adult, primary, nonstatus 1 candidates who were listed and subsequently underwent LT (n=270), or were removed because of death or clinical deterioration (n=277). Of the HCC candidates removed from the waitlist (n=184), 5.5% died waiting, 25.5% deteriorated clinically, and 69% had LT. Of the non-HCC candidates (n=363), 38.8% died waiting, 21.8% clinically deteriorated, and 39.4% had LT. Of the LT recipients, 127 (47%) had HCC. When compared with non-HCC transplant recipients, HCC recipients spent more time on the waitlist (435±475 vs 301±604 days, p=0.045) and from listing until LT had higher total pre-transplant hospital admissions per patient (1.1±1.2 vs 0.8±1.8, p<0.001). These admissions were more often planned (0.65±0.88 vs 0.17±0.52 planned admissions per patient, p<0.001) and of shorter duration (2.7±2.8 vs 5.2±4.6 days, p<0.001). The HCC and non-HCC recipients demonstrated similar overall post-transplant survival (5 year 80% vs. 83%, respectively; p=0.84). Despite a shorter wait to have LT, non-HCC candidates at our center have inferior waitlist outcomes. National reprioritization of liver allocation to improve access for non-HCC candidates may lead to increased wait time and resource use for the HCC population; however, a mortality benefit may exist for the non-HCC candidate lacking the benefit of time.

Prolonged Waiting-List Time Does Not Have a Negative Impact in the Post-Transplant Survival of Patients With Hepatocellular Carcinoma.

NTRODUCTION: The amount of time that patients with hepatocellular carcinoma (HCC) within the Milan criteria (MC) can safely remain on the waiting list for liver transplantation (LT) is unknown. AIM: We investigated whether a long waiting list (>6-months) impacts the post-transplant survival of HCC recipients. METHODS: This is a single-center retrospective study of adults with HCC within the MC, who were treated with TACE while on the waiting for a deceased donor LT. Patients were divided in groups according to waiting-list time (<3-months, 3-6months, 6-9 months, >9-months). The main endpoint was post-LT survival. RESULTS: 292 patients were selected as potential candidates and were listed for LT. A total of 187 patients underwent LT and met the eligibility criteria of the study. The median waiting time for LT for the entire cohort was 256 days (51-415 days). Mean follow-up after LT of the entire cohort of study was 2.2 years. There was a preponderance of white, middle-aged males with HCV with a biological MELD score of 13±5.2. Donors were usually middle-aged men, who died of cerebrovascular accident, and were transplanted at an average of 8.6±2 hours of cold ischemia. The average DRI was 1.6±0.3. Other donor and transplant characteristics were equivalent for all groups of the study. The dropout rate of the study cohort at 3, 6, and 12-months were 5.8%, 12.3%, and 16.1%, respectively. Post-LT survival did not differ based on the time on the waiting-list. Within the subgroup of patients with the longest waiting-list time, MELD score at transplant considerably influenced post-transplant survival, while alphafetoprotein level, tumor size, and response to TACE did not. Univariate and multivariate analysis failed to identify risk factors for worse survival on the subgroup of patients with long waiting-list time. The biological MELD was the only factor that independently impacted post-transplant survival in our multivariate analysis (p<0.001, HR=1.14). There was no linear relationship between waiting-list time and post-transplant survival (AUC=0.53, p=0.62). CONCLUSION: Waiting-list time had no relation with post-LT survival. MELD impacts post-transplant survival of all HCC patients independently of waiting-list time. Allocation policies that prolong waiting-list time for HCC candidates may not impact post-LT survival.

Inferior survival in liver transplant recipients with hepatocellular carcinoma receiving donation after cardiac death liver allografts

The impact of ischemia/reperfusion injury in the setting of transplantation for hepatocellular carcinoma (HCC) has not been thoroughly investigated. The present study examined data from the Scientific Registry of Transplant Recipients for all recipients of deceased donor liver transplants performed between January 1, 1995 and October 31, 2011. In a multivariate Cox analysis, significant predictors of patient survival included the following: HCC diagnosis (P < 0.01), donation after cardiac death (DCD) allograft (P < 0.001), hepatitis C virus-positive status (P < 0.01), recipient age (P < 0.01), donor age (P < 0.001), Model for End-Stage Liver Disease score (P < 0.001), recipient race, and an alpha-fetoprotein level > 400 ng/mL at the time of transplantation. In order to test whether the decreased survival seen for HCC recipients of DCD grafts was more than would be expected because of the inferior nature of DCD grafts and the diagnosis of HCC, a DCD allograft/HCC diagnosis interaction term was created to look for potentiation of effect. In a multivariate analysis adjusted for all other covariates, this interaction term was statistically significant (P = 0.049) and confirmed that there was potentiation of inferior survival with the use of DCD allografts in recipients with HCC. In conclusion, patient survival and graft survival were inferior for HCC recipients of DCD allografts versus recipients of donation after brain death allografts. This potentiation of effect of inferior survival remained even after adjustments for the inherent inferiority observed in DCD allografts as well as other known risk factors. It is hypothesized that this difference could reflect an increased rate of recurrence of HCC.

Donor Factors Similarly Impact Survival Outcome After Liver Transplantation in Hepatocellular Carcinoma and Non-hepatocellular Carcinoma Patients

Many have advocated the preferential use of high risk allografts for hepatocellular carcinoma patients undergoing liver transplantation. Hepatocellular carcinoma (HCC) patients tend to have relatively preserved liver function, and their outcome is felt to be driven largely by tumor-related factors. The aim of this study was to compare the relative importance of donor versus recipient factors on post-orthotopic liver transplantation survival among HCC and non-HCC recipients. The study group included Scientific Registry of Transplant Recipients data on adult recipients of deceased donor liver transplants from February 2002 through December 2008. Recipients were classified as HCC based on MELD exception applications and were compared to all other recipients. Predictors of post-LT survival were identified by Cox regression. To test whether donor factors have less impact on survival in HCC patients, interaction terms were created between HCC diagnosis and donor factors. Of the 40,212 DDLTs during the study period, 29,020 (72 %) met study criteria. A total of 7,786 (27 %)were transplanted with a diagnosis of HCC. The mean donor risk index was 1.5 in both cohorts. The 1-/5-year survival was 88 %/68 % and 87 %/74 % among HCC and non-HCC recipients, respectively (p\0.0001). On multivariate analysis, there was no statistically significant interaction between HCC diagnosis and DRI (HR 0.94,p = 0.317). Likewise, no interaction was seen between HCC diagnosis and individual donor factors. In both groups, donor and recipient factors carried similar weight in determining post-LT survival. Contrary to previous assumptions, donor factors play a similar role in determining survival post-LT among HCC patients and non-HCC patients.

Consequences of the Implementation of the Model for End-stage Liver Disease System for Liver Allocation in Brazil

BackgroundIn July 2006, the system for liver allocation in Brazil started to rely on the Model for End-stage Liver Disease (MELD) scale, replacing the previous chronological criteria. Under the new system, the score for listing pediatric patients is obtained by multiplication of the calculated PELD score by 3. The current criteria also features extra points for diseases such as hepatocellular carcinoma (HCC). This study sought to analyze the consequences of implementation of the MELD system on waiting list mortality, posttransplant survival rates and characteristics of the transplanted patients. MethodsWe retrospectively studied data from the State Health Secretariat of São Paulo, regarding all patients registered on the waiting list for liver transplantation in the State of São Paulo, in two periods: July 2005 to July 2006 (pre-MELD era) and July 2006 to July 2010 (MELD era). Patient survival rates calculated using the Kaplan-Meier method were compared by the log-rank test. P values <.05 were considered statistically relevant. ResultsAfter implementation of the MELD, waiting list registrations decreased by 39.8%; the percentage of transplants in HCC recipients increased from 2.4% to 23.7%; pediatric transplants increased from 6.5% to 9.3%; deaths on the list fell from 599 in the pre-MELD era to 359 in the last year analyzed; recipients with higher MELD displayed significantly lower posttransplant survival rates; HCC patients, better survival after transplantation (P = .002); No difference was observed comparing survival rates between pre-MELD and MELD eras (P = 474) or between adults and children (P = .867). ConclusionUnder the MELD system for liver allocation in Brazil, there was a reduction in waiting list mortality and an increased number of transplantations in pediatric and HCC recipients. Survival rates of patients with higher MELD score were inferior. However, this result was offset by the greater survival in HCC recipients, with no difference in patient survival rates between the pre-MELD and MELD eras.

Outcome of Liver Transplantation for Hepatocellular Carcinoma - a Single Center Experience

Background: Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). However, HCC recurrence remains a concern for 10-20% of patients. The aim of the study was to evaluate our experience regarding clinical and pathological staging, short and long-term survival after LT for HCC. Methods: From January 2006 to December 2011, 38 patients with diagnosis of HCC, including 30 men (78.9%) and 8 women (21.1%) of median age 52.3±7.7 years (range 27-64), underwent LT. Demographic, clinical, imaging and pathologic information were recorded. A Cox regression analysis was performed. Results: Six (15.8%) patients were classified as BCLC stage A, 21 (55.3%) - stage B, 5 (13.2%) - stage C and 6 (15.8%) - stage D. Eighteen patients (47.4%) were within Milan criteria. Six patients had radiofrequency ablation and 8 underwent chemoembolization as pretransplant bridging therapies. The median follow-up was 17.9 months and the recurrence rate of HCC after LT was 13.2%. Median time to HCC recurrence was 14.5 months. The 1, 3 and 5-year overall survival rates were 83.5%, 63.6% and 46.4% respectively. The 1, 3 and 5-year recurrence free survival rates were 85%, 74.3% and 74.3% respectively. Multivariate analysis identified presence of diabetes mellitus (p=0.001) and HCC recurrence (p=0.04) as independent risk factors for death after LT. Patients within Milan criteria, but with HCC recurrence, had a lab MELD score >18 at LT (50% vs 0%, p=0.004), AFP >100 ng/ml (100% vs 11.1%, p=0.03), progression of HCC nodules after bridging therapy (100% vs 0%, p=0.008), BCLC stage D (50% vs 6.3%, p=0.05). Conclusion: In our cohort HCC recurrence rate is 13.2% (47.4% patients within Milan criteria). Diabetes mellitus at LT and HCC recurrence influence long-term overall survival in HCC recipients.

Mortality risk after liver transplantation in hepatocellular carcinoma recipients: A nonlinear predictive model

The balanced application of a model for the estimate of outcomes of liver transplantation, in concert with assessment of disease severity, would not only improve transplant outcomes and maximize patient benefit from transplantation, but also facilitate informed decision making by patients and their relatives when considering transplantation. So far, however, linear discriminating methods have failed to attain sufficient power to predict post-transplant prognosis. Therefore, our aim was to develop a cancer-specific prognostic model by a nonlinear methodology based on pretransplant characteristics. With data collected retrospectively from 290 liver transplant recipients with HCC from February 1999 to August 2009, a multilayer perceptron (MLP) neural network was constructed to predict mortality risk after transplantation. Its predictive performances at posttransplant 1-, 2-, and 5-year intervals were evaluated using a receiver operating characteristic curve. By the forward stepwise selection in MLP network, donor age, donor body mass index, recipient hemoglobin, serum concentrations of total bilirubin, alkaline phosphatase, creatinine, aspartate aminotransferase, international normalized ratio of prothrombin time, and Na(+); alpha fetoprotein categorization, total diameter, number of tumor lesions, presence of imaging macrovascular invasion, and lobe distribution of the tumor were identified to be the optimal input features. The MLP, employing 24 inputs and 7 hidden neurons, yielded c-statistics of 0.909 (P < .001) in the 1-year, 0.888 (P < .001), in the 2-year, and 0.845 (P < .001) in the 5-year prediction. Post-transplant prognosis is a multidimensional, nonlinear problem, and the specific MLP can achieve high accuracy in the prediction of posttransplant mortality risk for HCC recipients. The pattern recognition methodologies like MLP hold promise for solving outcome prediction after liver transplantation.

Can the Dropout Risk of Candidates with Hepatocellular Carcinoma Predict Survival after Liver Transplantation?

In the last US national conference on liver transplantation for hepatocellular carcinoma (HCC), a continuous priority score, that incorporates model for end-stage liver disease (MELD), alpha-fetoprotein and tumor size, was recommended to ensure a more equitable liver allocation. However, prioritizing highest alpha-fetoprotein levels or largest tumors may select lesions at a higher risk for recurrence; similarly, patients with higher degree of liver failure could have lower postoperative survival. Data from 300 adult HCC recipients were reviewed and the proposed HCC-MELD equation was applied to verify if it can predict post-transplantation survival. The 5-year survival and recurrence rates after transplantation were 72.8 and 13.5%, respectively. Cox regression analysis confirmed HCC-MELD as predictive of both postoperative survival and recurrence (p < 0.001). The 5-year predicted survival and recurrence rates were plotted against the HCC-MELD-based dropout probability: the higher the dropout probability while on waiting list, the lower the predicted survival after transplantation, that is worsened by hepatitis C positivity; similarly, the higher the predicted HCC recurrence rate after transplantation. The HCC priority score could predict the postoperative survival of HCC recipients and could be useful in selecting patients with greater possibilities of survival, resulting in higher post-transplantation survival rates of HCC populations.

Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States

A national conference was held to better characterize the long-term outcomes of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) and to assess whether it is justified to continue the policy of assigning increased priority for candidates with early-stage HCC on the transplant waiting list in the United States. The objectives of the conference were to address specific HCC issues as they relate to liver allocation, develop a standardized pathology report form for the assessment of the explanted liver, develop more specific imaging criteria for HCC designed to qualify LT candidates for automatic Model for End-Stage Liver Disease (MELD) exception points without the need for biopsy, and develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions. At the completion of the meeting, there was agreement that the allocation policy should result in similar risks of removal from the waiting list and similar transplant rates for HCC and non-HCC candidates. In addition, the allocation policy should select HCC candidates so that there are similar posttransplant outcomes for HCC and non-HCC recipients. There was a general consensus for the development of a calculated continuous HCC priority score for ranking HCC candidates on the list that would incorporate the calculated MELD score, alpha-fetoprotein, tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors would receive additional HCC priority points.