Liver Transplantation In Hepatocellular Carcinoma Patients Research Articles

A predictive model based on radiomics, clinical features, and pathologic indicators for disease-free survival after liver transplantation for hepatocellular carcinoma: a 7-year retrospective study.

Disease-free survival (DFS) is an essential indicator for evaluating the prognosis of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients. Despite progress in the prediction of DFS by radiomics, only preoperative clinical features have been combined in most studies. The aim of this study was to construct a nomogram model (NM) using preoperative clinical features, radiomics, and postoperative pathological indicators for more effective prediction of DFS. This was a retrospective study of a single-center cohort comprising 139 HCC patients. Using the whole cohort, we constructed and assessed a clinical model (CM) based on alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), a pathological model (PM) based on Ki-67 and tumor number, a radiomics model (RM) based on the radiomics score (Rad-score), and an NM based on the above five independent predictors. Significant correlations between the NM and DFS were observed in the training and validation cohorts. Among the four prediction models, the C-index of the NM was the highest [(training/validation cohort) CM: 0.664/0.676, PM: 0.737/0.691, RM: 0.706/0.697, NM: 0.817/0.760], and the areas under the receiver operating characteristic curves (AUCs) of the NM prediction of 1-year, 2-year, and 3-year DFS were also the highest [(training/validation cohort) 1-year, 2-year, and 3-year CM: 0.726/0.726, 0.685/0.744, 0.645/0.686, PM: 0.789/0.780, 0.801/0.748, 0.841/0.735, RM: 0.769/0.752, 0.717/0.805, 0.748/0.765, NM: 0.882/0.854, 0.867/0.849, 0.882/0.801]. The NM also exhibited the highest net clinical benefit. Based on radiomics, clinical features, and pathological indicators, the NM could be used to effectively predict DFS after LT in HCC patients, guiding the follow-up and complementary treatment.

Correlation between 18 F-FDG PET/CT metabolic parameters and microvascular invasion before liver transplantation in patients with hepatocellular carcinoma.

Microvascular infiltration (MVI) before liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is associated with postoperative tumor recurrence and survival. MVI is mainly assessed by pathological analysis of tissue samples, which is invasive and heterogeneous. PET/computed tomography (PET/CT) with 18 F-labeled fluorodeoxyglucose ( 18 F-FDG) as a tracer has been widely used in the examination of malignant tumors. This study investigated the association between 18 F-FDG PET/CT metabolic parameters and MVI before LT in HCC patients. About 124 HCC patients who had 18 F-FDG PET/CT examination before LT were included. The patients' clinicopathological features and 18 F-FDG PET/CT metabolic parameters were recorded. Correlations between clinicopathological features, 18 F-FDG PET/CT metabolic parameters, and MVI were analyzed. ROC curve was used to determine the optimal diagnostic cutoff value, area under the curve (AUC), sensitivity, and specificity for predictors of MVI. In total 72 (58.06%) patients were detected with MVI among the 124 HCC patients. Univariate analysis showed that tumor size ( P = 0.001), T stage ( P < 0.001), maximum standardized uptake value (SUV max ) ( P < 0.001), minimum standardized uptake value (SUV min ) ( P = 0.031), mean standardized uptake value (SUV mean ) ( P = 0.001), peak standardized uptake value (SUV peak ) ( P = 0.001), tumor-to-liver ratio (SUV ratio ) ( P = 0.010), total lesion glycolysis (TLG) ( P = 0.006), metabolic tumor volume (MTV) ( P = 0.011) and MVI were significantly different. Multivariate logistic regression showed that tumor size ( P = 0.018), T stage ( P = 0.017), TLG ( P = 0.023), and MTV ( P = 0.015) were independent predictors of MVI. In the receiver operating characteristic curve, TLG predicted MVI with an AUC value of 0.645. MTV predicted MVI with an AUC value of 0.635. Patients with tumor size ≥5 cm, T3-4, TLG > 400.67, and MTV > 80.58 had a higher incidence of MVI. 18 F-FDG PET/CT metabolic parameters correlate with MVI and may be used as a noninvasive technique to predict MVI before LT in HCC patients.

Hepatocellular Carcinoma: The Evolving Role of Systemic Therapies as a Bridging Treatment to Liver Transplantation.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curative for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists and/or to downstage patients who are beyond the Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine kinase inhibitors (TKIs) can be used as a systemic bridging therapy to LT in patients with contraindications for locoregional liver-directed therapies. Immune checkpoint inhibitor (ICI) treatment can be utilized either as a monotherapy or as a combination therapy with bevacizumab or TKIs prior to LT. Acute rejection after liver transplantation is a concern in the context of ICI treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Long-Term Outcomes of Liver Transplantation in Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Comparison with Portal Vein Tumor Thrombus.

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial. This study analyzed the recurrence and overall survival rates through long-term results after LT in HCC patients with BDTT and compared the results after LT in HCC patients with portal vein tumor thrombus (PVTT). We performed a retrospective study of 45 patients with PVTT, 16 patients with BDTT, and 11 patients with coexisting PVTT and BDTT among HCC patients who underwent LT at a single center from 1999 to 2020. The HCC recurrence rates were 40.4% at 1 year, 30.3.3% at 2 years, and 27.6% at 3 years in the PVTT group; 66.7%, 53.3%, and 46.7% in the BDTT group; and 22.2%, 22.2%, and 0% in the coexisting group (p = 0.183). Overall patient survival rates were 68.4% at 1 year, 54.3% at 2 years, and 41.7% at 3 years in the PVTT group; 81.3%, 62.5%, and 48.2% in the BDTT group; and 63.6%, 27.3%, and 0% in the coexisting group (p = 0.157). In the multivariate analysis, the pre-transplantation model for tumor recurrence after liver transplantation (MoRAL) score and model for end-stage liver disease (MELD) score were found to be independent risk factors for recurrence and survival in all groups. HCC patients with BDTT showed no difference in recurrence and survival compared with HCC patients with PVTT at the long-term follow-up after LT.

Safety of Intraoperative Blood Salvage During Liver Transplantation in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Objective:The effects of intraoperative blood salvage (IBS) on time to tumor recurrence, disease-free survival and overall survival in hepatocellular carcinoma (HCC) patients undergoing liver transplantation were assessed to evaluate the safety of IBS.Background:IBS is highly effective to reduce the use of allogeneic blood transfusion. However, the safety of IBS during liver transplantation for patients with HCC is questioned due to fear of disseminating malignant cells.Methods:Comprehensive searches through June 2021 were performed in 8 databases. The methodological quality of included studies was assessed using the Robins-I tool. Meta-analysis with the generic inverse variance method was performed to calculate pooled hazard ratios (HRs) for disease-free survival, HCC recurrence and overall survival.Results:Nine studies were included (n=1997, IBS n=1200, no-IBS n=797). Use of IBS during liver transplantation was not associated with impaired disease-free survival [HR=0.90, 95% confidence interval (CI)=0.66–1.24, P=0.53, IBS n=394, no-IBS n=329], not associated with increased HCC recurrence (HR=0.83, 95% CI=0.57–1.23, P=0.36, IBS n=537, no-IBS n=382) and not associated with impaired overall survival (HR=1.04, 95% CI=0.79–1.37, P=0.76, IBS n=495, no-IBS n=356).Conclusions:Based on available observational data, use of IBS during liver transplantation in patients with HCC does not result in impaired disease-free survival, increased HCC recurrence or impaired overall survival. Therefore, use of IBS during liver transplantation for HCC patients is a safe procedure.

Preoperative Prognostic Nutritional Index May Be a Strong Predictor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

PurposeMalnutrition is a major risk factor of immune dysfunction and poor outcome in cancer patients. The prognostic nutritional index (PNI), which is established by serum albumin level and peripheral lymphocyte count, was shown to correlate with prognosis of hepatocellular carcinoma (HCC) patients following liver resection and non-surgical interventions. The aim of this study was to analyze the predictive value of preoperative PNI in liver transplantation (LT) patients with HCC.Patients and MethodsA total of 123 HCC patients that underwent LT were included in the analysis. The prognostic impact of preoperatively assessed clinical factors including the PNI on post-LT outcome was analyzed by uni- and multivariate analysis.ResultsPost-transplant tumor recurrence rates were 5.1% in high-PNI (> 42) and 55.6% in low-PNI (≤ 42) patients (p < 0.001). Preoperative high-PNI could be identified as a significant and independent promoter of both recurrence-free survival (hazard ratio [HR] = 10.12, 95% CI: 3.40–30.10; p < 0.001) and overall survival (HR = 1.69, 95% CI: 1.02–2.79; p = 0.004) following LT. Apart from that low-PNI proved to be a significant and independent predictor of microvascular tumor invasion (OR = 7.71, 95% CI: 3.17–18.76; p < 0.001). In contrast, no tumor morphology features including the Milan criteria revealed an independent prognostic value.ConclusionOur data indicate that preoperative PNI correlates with biological tumor aggressiveness and outcome following LT in HCC patients and may therefore be useful for refining oncologic risk stratification.

DNA and RNA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation.

BACKGROUNDOxidative damage of DNA and RNA has been associated with mortality of patients with different diseases. However, there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).AIMTo determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis.METHODSPatients with HCC who underwent LT were included in this observational and retrospective study. Serum levels of all three oxidized guanine species (OGS) were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation. LT mortality at 1 year was the end-point study.RESULTSSurviving patients (n = 101) showed lower serum OGS levels (P = 0.01) and lower age of the liver donor (P = 0.03) than non-surviving patients (n = 13). An association between serum OGS levels prior to LT and 1-year LT (odds ratio = 2.079; 95% confidence interval = 1.356-3.189; P = 0.001) was found in the logistic regression analysis.CONCLUSIONThe main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.

Preoperative Alpha-Fetoprotein and Radiological Total Tumor Diameter as Predictors of Hepatocellular Carcinoma Recurrence After Liver Transplantation

Liver transplantation is a unique treatment opportunity for patients with chronic liver disease and hepatocellular carcinoma (HCC). Selection of HCC patients for transplantation was revolutionized by Milan-based criteria, but tumor recurrence and shortage of organs are still a major concern. Nowadays, additional preoperative tumor parameters can help to refine the graft allocation process. The objective of this study was to evaluate the prognostic value and cut-off points of pretransplant serum alpha-fetoprotein (AFP) levels and radiological tumor parameters on liver transplantation outcomes. This is a single-team retrospective cohort of 162 consecutive deceased donor liver transplants (DDLT) with pathologically confirmed HCC. Pretransplant serum AFP levels and radiological tumor parameters were retrieved from a preoperative follow-up. Receiver-operating characteristics (ROC) curves were used to evaluate cut-off points for each outcome. Multivariate Cox regression model was used to assess the predictors of HCC relapse and recipient mortality. Twelve recipients (7.4%) had HCC recurrence after transplantation, with median survival time of 5.8 months. Pretransplant AFP ≥30 ng/mL (hazard ratio [HR]: 13.84, P=.003) and radiological total tumor diameter (TTD) ≥5 cm (HR: 12.89, P=.005) were independent predictors for HCC relapse. Moreover, pretransplant AFP ≥150 ng/mL was independently associated with recipient mortality (HR: 4.45, P=.003). Pretransplant AFP levels and radiological TTD were independently associated with HCC relapse and recipient mortality after DDLT, with different cut-off points predicting different outcomes. These findings may contribute to improving decision-making in the context of liver transplantation for HCC patients.

Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization?

BackgroundIn hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment.MethodsWe retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival.ResultsBetween groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1–2] vs. 1 [1–7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death.ConclusionsIntraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.

Patient Selection for Downstaging of Hepatocellular Carcinoma Prior to Liver Transplantation-Adjusting the Odds?

Background and Aims: Morphometric features such as the Milan criteria serve as standard criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Since it has been recognized that these criteria are too restrictive and do not adequately display the tumor biology, additional selection parameters are emerging. Methods: Concise review of the current literature on patient selection for downstaging and LT for HCC outside the Milan criteria. Results: The major task in patients outside the Milan criteria is the need for higher granularity with patient selection, since the benefit through LT is not uniform. The recent literature clearly shows that beneath tumor size and number, additional selection parameters are useful in the process of patient selection for and during downstaging. For initial patient selection, the alpha fetoprotein (AFP) level adds additional information to the size and number of HCC nodules concerning the chance of successful downstaging and LT. This effect is quantifiable using newer selection tools like the WE (West-Eastern) downstaging criteria or the Metroticket 2.0 criteria. Also an initial PET-scan and/or tumor biopsy can be helpful, especially in the high risk group of patients outside the University of California San Francisco (UCSF) criteria. After this entry selection, the clinical course during downstaging procedures concerning the tumor and the AFP response is of paramount importance and serves as an additional final selection tool. Conclusion: Selection criteria for liver transplantation in HCC patients are becoming more and more sophisticated, but are still imperfect. The implementation of molecular knowledge will hopefully support a more specific risk prediction for HCC patients in the future, but do not provide a profound basis for clinical decision-making at present.

Liver transplantation for hepatocellular carcinoma at Centro Médico Nacional 20 de Noviembre-México

Hepatocellular carcinoma (HCC) incidence is rising worldwide, actually it's the third cause of cancer associated death. The main risk factor are hepatitis B and C viral infection. In Mexico we have around 6,000 deaths each-yfrom HCC each-year. Liver transplantation for HCC within Milan criteria is the best curative intention. We conducted a descriptive analysis from cirrhotic HCC patients that underwent a liver transplantation (LT) between January 2015 to July 2019. Our policy for LT in HCC patients is Milan criteria, for patients beyond that we perform downstaging procedures such as transarterial chemoenbolization (TACE), microwave or radiofrequency ablation. We analyze disease free and overall survival, recurrence, morbidity and mortality. 15 patients underwent LT for HCC. We divide patients in two groups: Group 1 within Milan (n = 10) and Group 2 beyond Milan (n = 5). Group 2 patients underwent downstaging locoregional therapy by means of radiofrequency or microwave ablation and TACE. The disease free survival at 1-year was 100% in both groups. At 4-year follow up overall survival was 66.6%. During the follow up period none of the patients developed HCC recurrence. Overall 5-year survival for LT and HCC is reported 60-70% mostly associated to HCC recurrence but in our study global survival was 66.6% but no mortality was associated to HCC recurrence. Within Milan group showed better survival rates than downstaged group, but since both groups developed no HCC recurrence, we still believe downstaging policy is a good strategy for HCC beyond Milan criteria.

Hepatocellular Carcinoma and the Role of Liver Transplantation: A Review.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.

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.

Acute rejection after liver transplantation is less common, but predicts better prognosis in HBV-related hepatocellular carcinoma patients.

With a novel finding of significantly lower incidence of acute rejection (AR) in patients with hepatocellular carcinoma (HCC) after liver transplantation, compared with those with benign end-stage liver disease (BESLD), in a large national cohort, we analyzed the correlations among the perioperative immuno-inflammation status, postoperative AR, and prognosis in HCC and BESLD patients with same etiology of hepatitis B virus (HBV), who underwent liver transplantation. Patients who underwent liver transplantation due to HBV-related HCC or BESLD and experienced AR between September 2008 and April 2017 were analyzed retrospectively and followed up until April 2018. HCC patients with AR were matched with those without AR according to tumor stage and immunosuppressant concentration, at a 1:3 ratio. Preoperative immuno-inflammation status and prognosis of patients in both groups were compared. The overall incidences of AR in patients with HCC and BESLD were 8.60% and 10.61%, respectively. The postoperative 28-day incidence of AR was significantly lower in HCC compared with BESLD patients (3.23% vs 7.08%, p = 0.031). Compared with BESLD patients, the rejection activity index and perioperative CD4/CD8 ratio were significantly lower (p = 0.047 and p < 0.001, respectively), while platelet/lymphocyte ratio was significantly higher in HCC patients (p = 0.041). Later tumor stage in HCC patients was associated with higher systemic immuno-inflammation index, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, platelet/lymphocyte ratio, aspartate aminotransferase/lymphocyte ratio, C-reactive protein/albumin ratio and fibrinogen level, and lower CD4/CD8 ratio before transplantation. In HCC patients with AR, the percentage of regulatory T cells (CD4+/CD25+) and the level of IL-10 significantly decreased (p = 0.0023, < 0.0001, respectively), while Th1/Th2 ratio, levels of IFN-γ and IL-2 markedly increased before transplantation (p = 0.0018, 0.0059, 0.0416, respectively). Preoperative monocyte/lymphocyte ratio was an independent risk factor for overall and recurrence-free survival after liver transplantation in HCC patients (p = 0.025, < 0.001, respectively). The 1-, 3-, and 5-year survival rates were 76%, 71% and 53% in the AR group, and 67%, 37% and 25% in the non-AR group (p = 0.042). Preoperative tumor-related immunosuppression may persist after liver transplantation in HCC patients, and reduce the incidence of AR. AR after liver transplantation may indicate a better prognosis in HCC patients.

118.6: Oncologic outcomes of ABO-incompatible living donor liver transplantation for HCC patients.

Background: ABO incompatible living donor liver transplantation (ABOi LDLT) could be one of the treatment options for hepatocellular carcinoma (HCC) to overcome organ scarcity. However, desensitization protocol including B cell depletion besides traditional T cell suppression could be a risk factor for HCC recurrence that is a major cause of graft failure and patient death. We analyzed oncologic outcomes of ABOi LDLT comparing to ABO compatible LDLT. Methods: The data of 101 recipients who underwent LDLT for HCC were prospectively collected and reviewed. Of the patients, 21 patients underwent ABOi LT. We compared the pre- and post-transplant tumor factors, HCC recurrence and survival between ABOi and ABOc LT. Results: There was no significant difference in pre-transplant tumor staging, recipient and donor demographics between the groups. One and 3-year recurrence-free survival rates were 89.8% and 86.9% for the ABOc LT group and 85.4% and 80.1% for the ABOi LT, respectively (P=0.439; Fig 1). One and 3-year overall survival rates were 96.3% and 88.1% for the ABOc LT group and 90.5% and 85.2% for the ABOi LT, respectively (P=0.651; Fig 2). In multivariate analysis, a pre-transplant AFP level over 400 ng/mL was the only independent risk factor for HCC recurrence and poor patient survival. Conclusions: The HCC recurrence survival and overall survival of ABOi LT were comparable to those of ABOc LT. ABOi LT is safe and feasible option for HCC patients.

Downstaging and Expanded Criteria Hepatocellular Carcinoma Liver Transplantation

Liver transplantation (LT) has been utilized in the last two decades for the treatment of selected patients with hepatocellular carcinoma (HCC). Currently, in most jurisdictions worldwide, only tumor size and number determine transplant candidacy, which may not sufficiently predict tumor behavior. Both tumor downstaging and expanding transplant criteria play an important role in expanding access to LT for HCC patients. New downstaging protocols are emerging that incorporate response to locoregional therapies (LRT) among those that initially present beyond the accepted Milan criteria. In parallel, new serologic, histologic, and radiographic tools are being identified that may better predict outcomes after LT for HCC, in so-called extended criteria. The efforts of different jurisdictions worldwide in creating new treatment protocols have made it possible to evaluate and compare outcomes of patients over time. Improvements of LRT and expansion of the criteria for LT for HCC will both play a role in optimizing outcomes for patients with HCC.

Liver transplantation for hepatic tumors: A small center experience

The aim of this study was to retrospectively analyze the data of patients undergoing liver transplantation (LT) for hepatic tumors (HT). We present the results of diagnosis and treatment for HT with LT. The study included 17 patients, 12 males and 5 females, aged 25 to 69 years. The main indication for LT was hepatocellular carcinoma (HCC) under the Milan criteria in 13 cases, cholangiocarcinoma (CCA) in one case, hepatic epithelioid hemangioendothelioma (HEHE) in two cases and adenomatosis hepatis (AH) in one case. The history of the underlying disease of HT ranged from 5 to 20 years and the history of HT diagnosis history ranged from zero to 5 years. The waiting time for LT was one to 48 months. One-year survival rate for the HCC patients was 69% (9/13). Regrettably, two of them whose tumor progressed beyond the Milan criteria during waiting time, possibly associated with liver biopsy, died due to HCC recurrence. The mistakenly transplanted CCA patient died four months later due to tumor recurrence. The general condition of the HEHE and AH patients has been good over 5 years after LH. However, one HEHE patient had extra-and intrahepatic recurrence.In conclusion, recent guidelines for HCC diagnosis, based on frequent radiological imaging alone, without confirming biopsy, may improve the results of LT for HCC patients. At small canters, LT for CCA is not yet practicable. LT is a promising procedure for HEHE and AH patients even in advanced and recurrent cases at all centers.

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: A Single-Center Experience.

BackgroundThere is a worldwide increase in use of liver transplantation (LT) for treatment of hepatocellular carcinoma (HCC). We analyzed our experience with LT for HCC to determine long-term and recurrence-free survival, accuracy of imaging diagnosis of HCC compared to the explant pathology, recurrence rate of HCC, and predictors of recurrence.Material/MethodsThe whole explant was examined by the same pathologist and compared with the baseline diagnosis established according to clinical, laboratory, and radiological data. A group of patients with pathologically confirmed HCC was characterized, with special attention to etiology, survival, recurrence, and diagnostic accuracy of imaging techniques.ResultsAmong 718 patients transplanted from 2000 to 2018 in our center, HCC was found in 166 explanted livers. In 42 cases the clinical diagnosis of HCC was not accurate, being either false positive or negative; however, the specificity and sensitivity of CT/MRI in HCC recognition was 97.87% and 88.24%, respectively. Five- and 10-year survival was 81.27% and 66.57%, respectively, and it was inferior to the overall survival. The recurrence rate was 9.6% with a median time to recurrence of 14 months and a median survival time of 9 months. Poor differentiation of HCC and HCV etiology of the baseline disease, but not previous DAA treatment, were the risk factors of HCC recurrence.ConclusionsAdherence to strictly defined selection criteria for LT in HCC patients guarantees the success of LT in HCC treatment.

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers, is the second leading cause of cancer-related deaths and the leading cause of death in patients with cirrhosis. Liver transplantation (LT) represents the ideal treatment for selected patients as it removes both the tumor and the underlying cirrhotic liver with 5-year survival rates higher than 70%. Unfortunately, due to tumor characteristics, patient co-morbidities or shortage of organs available for transplant, only 20% of patients can undergo curative treatment. Ex situ machine perfusion (MP) is a technology recently introduced that might potentially improve organ preservation, allow graft assessment and increase the pool of available organs. The purpose of this review is to provide an update on the current role of ex situ liver MP in liver transplantation for HCC patients.

Bridging to liver transplantation in HCC patients.

Liver transplantation (LT) is the only cure for patients diagnosed with unresectable hepatocellular carcinoma (HCC), and HCC has become the leading indication for LT in the USA. The shortage of liver grafts results in a significant waiting time for LT with the risk of tumour progression. Treating HCCs during the waiting time prior to transplantation (bridging therapy) is an attractive strategy to reduce the risk of exceeding the tumour criteria for transplantation. Studies on bridging therapy are heterogenous and due to ethical issues, mostly of retrospective design. We summarize the main studies and methods that have been reported on bridging therapies for patients with HCC waiting for a LT. During the waiting period for LT, patients with HCC at risk for tumour progression and therefore bridging therapy is recommended for patients with an estimated waiting time of ≥6months. Bridging therapy for patients with HCC prior to LT mainly include locoregional therapies (LRTs), with transarterial chemoembolization (TACE) being the most common, followed by radio frequency ablation (RFA). Because of a continuous enhancement of therapy options, including a more precise adjustment of external radiotherapy, further possibilities for an individualized bridging therapy for patients with HCC have been developed. Patients with compensated liver cirrhosis and small tumour size are preferably treated with RFA, whereas patients with larger tumour size but compensated liver function are treated with TACE/TARE. Patients with uncompensated liver cirrhosis and larger tumour size can nowadays be successfully bridged to LT with external radiotherapy without increasing the risk for further deterioration of liver function.