Underwent Liver Transplantation For Hepatocellular Carcinoma Research Articles

Potential impact of malnutrition on patients with hepatocellular carcinoma undergoing liver transplantation: A nationwide analysis.

e16233 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide. Liver transplantation is the ideal treatment for HCC, and the Milan criteria, which has been the international gold standard, provided the opportunity for HCC patients to undergo liver transplantation with favorable outcomes. On the other hand, malnutrition is a prevalent condition, and carries a substantial burden on health and social-care systems. In this study, we aim to look at the potential impact of malnutrition on in-hospital mortality and other outcomes in HCC patients undergoing liver transplantation. Methods: The United States Nationwide Inpatient Sample (NIS) was used to extract hospitalization data of patients admitted between 2016 to 2018. Using ICD10 revision codes, we identified adults with a diagnosis of HCC, with or without cirrhosis, who underwent liver transplantation with concomitant malnutrition. The control group included HCC patients without malnutrition. The primary outcome was the in-hospital mortality. Secondary outcomes included length of stay (LOS), acute kidney injury (AKI) and hyponatremia. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 33,321 patients were admitted with HCC during the study period. 503 of them underwent liver transplantation, and of those, 75 patients had the diagnosis of malnutrition. In this group of patients, the mean age was 60.3 years. 30% were females and 60% were Caucasians. When adjusted to other relevant variables, malnutrition was associated with increased in-hospital mortality (OR 2.42; P-value 0.033). It was also associated with increased chance of developing an AKI (OR 1.95; P-value 0.014). Moreover, it was associated with increased LOS (OR 1.18) and increased chance of liver transplant rejection (OR 1.47), however, these were not statistically significant. Other factors associated with increased in-hospital mortality in HCC patients undergoing liver transplantation are described in the table. Conclusions: Malnutrition is a potentially treatable condition, however, when untreated it may contribute to poor health and economic outcomes. In this study, HCC patients with malnutrition who underwent liver transplantation, have an increased chance of in-hospital mortality. Furthermore, they had an increased odds of developing an AKI which in turn can prolong the hospital length of stay and total charges. We recommend that clinicians pay more attention to identify patients with or at increased risk for malnutrition in order to treat and optimize them prior to liver transplantation, and therefore to prevent such complications. [Table: see text]

Analysis of the Effects of Preoperative Hepatic Artery Chemoembolization and Quality Nursing Intervention on the Perioperative Safety and Short-term Prognosis of Liver Transplantation in Patients with Hepatocellular Carcinoma

Objective: To investigate the effects of preoperative hepatic artery chemoembolization (TACE) and quality nursing interventions on the perioperative safety and short-term prognosis in patients with hepatocellular carcinoma undergoing liver transplantation. Methods: The study period spanned from January 2021 to December 2023, and 125 patients with hepatocellular carcinoma admitted to our hospital were selected, all of whom underwent liver transplantation. They were randomly divided into an observation group (n = 63) and a control group (n = 62). The patients in the control group did not undergo TACE before the operation, and the patients in the observation group underwent TACE and quality nursing intervention before the operation. The operation time, intraoperative blood loss, length of hospitalization, liver-free period, complication rate, short-term prognosis, and liver function indexes between the two groups were compared. Results: There was no significant difference in operation time, intraoperative blood loss, and length of hospitalization between the two groups (P < 0.05). The liver-free period of patients in the observation group was longer than that of the control group (P < 0.05). The two groups had no significant difference in the incidence of biliary complications, vascular complications, and postoperative infections (P > 0.05). The rate of immune reactive complications in the observation group was lower than that of the control group (P < 0.05). There was no significant difference in the perioperative mortality rate, 1-year postoperative survival rate, and 2-year postoperative survival rate (P > 0.05). The two groups had no significant difference in postoperative liver function indexes (P > 0.05). Conclusion: Preoperative TACE and high-quality nursing intervention in patients with hepatocellular carcinoma had no adverse effect on the perioperative safety and short-term prognosis, prolonged the liver-free time, and reduced the incidence of immune-reactive complications.

Prognostic role of platelet lymphocyte ratio (PLR) among patients with hepatocellular carcinoma undergoing liver transplantation

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, but it is so aggressive that is the third most common cause of cancer related death. We aim to study the role of PLR in prognosis of HCC and to see if it can be a predictor of overall survival and disease free survival among HCC patients that received liver transplantation in our centre. Patients and Methods This is a single centre retrospective analysis of prospectively collected data. The study was carried out in liver transplant institute of Inonu University, Malatya, Turkey. Consecutive patients that received liver transplantation for HCC and survive for at least 90 days post transplantation were included in the study. Data was collected regarding age, gender, presence or absence of cirrhosis, cause of cirrhosis, number of nodules, maximum size of the tumour, preoperative PLR, pre-transplant GGT, type of transplant, presence or absence of microvascular invasion, overall survival and disease free survival. The study was censored on June 2022. Data was analyzed using SPSS version 25. Results Platelet lymphocyte ratio was found to be significantly associated with some poor prognostic factors of HCC in our patients. We found that PLR is significantly associated with maximum tumour diameter (MTD) and total tumor diameter (TTD) with p= <0.0001 and 0.0016 respectively. Univariate analysis revealed that PLR is a predictor of worse DFS or OS but when subjected to multivariate analysis, we found that PLR is not an independent predictor of OS and DFS. Conclusion Platelet lymphocyte ratio is associated with poor prognostics feature of hepatocellular carcinoma.

Activated but impaired IFN-γ production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma

ObjectiveMucosal-associated invariant T (MAIT) cells are innate T cells with immunoregulatory activity and were recently found to be associated with various tumor types. The role of intrasinusoidal MAIT cells in...

Impact of Hypothyroidism on Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation.

BackgroundThis work endeavored to explore the effect of hypothyroidism on mortality in subjects with HCC who underwent living-donor liver transplantation (LDLT).MethodsThis prospective study included 107 patients with HCC subjected to LDLT, divided into hypothyroid group (n=53) and euthyroid group (n=54). The primary objectives were overall and disease-free survival (DFS).ResultsEuthyroid and hypothyroid groups were comparable in all baseline characteristics except the age of patients. Overall survival (OS) of the whole group at 48 months was 68.8%, while the DFS was 60.2%. On univariate analysis, OS was negatively affected by the older age of the patients (p<0.001) or the donor (p<0.001), hypothyroidism (p=0.008), HBV (p=0.029), larger tumor size (p=0.023), and defective Milan criteria (p=0.022). On multivariate analysis, the age of the patients and donors was the independent factor affecting OS. On univariate analysis, DFS was negatively affected by older age of the patients (p < 0.001) or the donor (p=0.005), hypothyroidism (p=0.005), HBV (p=0.019), larger tumor size (p=0.023), and defective Milan criteria (p=0.020). On multivariate analysis, the age of the patients, thyroid status, and Milan criteria were the independent factors affecting DFS.ConclusionHypothyroidism is a risk factor for worse outcomes in HCC patients after liver transplantation.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Predictors of 30-day readmission rate after liver transplant in patients with hepatocellular carcinoma.

e16193 Background: Liver transplantation (LT) is curative for hepatocellular carcinoma (HCC) in patients within the Milan criteria. Readmissions are common postoperatively, and can be associated with increased morbidity and healthcare burden. Hence we aim to identify incidence, impact and independent predictors for readmission in patients who underwent LT in HCC. Methods: Retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for LT with an underlying diagnosis of HCC, in patients with cirrhosis we used the BAVENO score to categorize between compensated and decompensated cirrhosis. We aim to identify 30-day readmission rate, mortality, healthcare related utilization resources and independent predictors of readmission. Results: A total of 2,092 patients with HCC underwent liver transplantation. The 30-day readmission rate was 25.6%. Main causes for readmission were post-surgical complications from LT, sepsis, liver failure. Readmitted patients were less likely to have private insurance (40.5% vs 34.5%; P&lt;0.01), to be obese (18.2% vs 7.9%; P&lt;0.01), hypertensive (51.2% vs 39.5%; P&lt;0.01), have history of non-alcoholic steatohepatitis (16.5% vs 2.3%; P&lt;0.01). Readmission was associated with higher in-hospital mortality rate (0.1% vs. 1.5%; P&lt;0.01). The total health care in-hospital economic burden of readmission was $56.1 million in total charges and $15.2 million in total costs. Independent predictors of readmission were type 2 diabetes, transfusion of blood products during index admission, protein-caloric malnutrition, sepsis, and preventive factors were younger age, private insurance and cannabis use. Conclusions: Readmissions after LT in HCC are associated with higher mortality and pose a high health care burden. We identified risk factors that can be targeted to decrease overall patient morbidity, mortality and health care burden.[Table: see text]

Oncological Evaluation Using Circulating Tumor Cells and PET-CT of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. Liver transplantation (LT) is potentially the best curative therapeutic option in selected cirrhotic patients (Milan criteria). Nevertheless, the recurrence rate is high (10-20%) and there are not efficient markers of biological pretransplant activity. Aim: to determine the number of CTCs in patients with HCC awaiting for LT, to study its possible association with AFP levels, positivity of PET-CT and clinical variables (vascular invasion, tumor size, waiting list time, post-LT recurrence…) and to compare CTC levels before and after LT (one and six months and one and two years). Method: Peripheral blood was obtained from 30 patients included in the waiting list and after 1 and 6 months and 1 and 2 years of the LT. CTCs immunomagnetic isolation was performed with anti-EpCAM antibodies by IsoFlux™ system. Statistical analysis: Rho Spearman test, Mann-Whitney U test and Wilcoxon test were used when appropriate (SPSS 22.0;Inc;USA). Results: A total of 30 patients with HCC within Milan criteria were included. The median follow-up was 57 months (IQR: 45-62). Four patients (13.3%) had a recurrence. Before LT, at least one CTC was counted in 24 patients (80%). The average concentration of CTCs before LT was 9(IR:0-93) CTCs/10 ml. At 1 and 6 months, 1 and 2 years of LT, CTC levels were 4(IR:1-22), 3(IR:0-20), 2(IR:0-6) and 3(RI:1-9) CTCs/10 ml respectively. Statistically significant differences were found between pre-LT levels and CTC levels at one year (Z = - 2.375;p = 0.018) and at 2 years (Z = - 2.076;p = 0.038).Pre-LT levels of CTC were associated with a prolonged time on the waiting list (rs = 0.550;p = 0.002), positive PET-CT (U = 25;z = - 2.250;p = 0.024), larger tumor size (rs = 0.570;p = 0.001), increase in the sum of the diameters of viable tumors (rs = 0.487;p = 0.006) and presence of microvascular invasion (U = 10;z = - 2.130;p = 0.033). The recurrence-free survival was lower in patients with SUVmax≥3.5 (log-rank 14.6;p<0.001) and pre-LT CTC levels≥9 (log-rank 4.2; p = 0.040). A correlation was found between CTC levels and the days on waiting list (p = 0.002), tumor size (p = 0.001), positive PET-CT (p = 0.024) and presence of microvascular invasion (p = 0.033). Recurrence-free survival was lower in patients with CTCs ≥ 9 (p = 0.040). Conclusion: CTC levels in patients with HCC undergoing LT are associated with clinical and pathological factors of poor prognosis.CTC levels decrease significantly after LT.

Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation

BackgroundRecurrence of hepatocellular carcinoma (HCC) is the main factor affecting the prognosis of patients with HCC undergoing liver transplantation (LT). In this study, we investigated the influencing factors of tumor recurrence and survival after LT for HCC, especially the long-term correlation with elevated fasting blood glucose (FBG). MethodsClinical data from 165 patients with HCC after LT in the General Hospital of Southern Theater Command of PLA between January 2013 and December 2016 were retrospectively analyzed. Disease-free survival (DFS) and overall survival (OS) rates, demographic characteristics, tumor characteristics, and surgical and postoperative data were evaluated. ResultsAmong 165 patients, 144 completed over 60 months of follow-up; the median follow-up period was more than 36 months. DFS rates were 76.97%, 51.52%, and 34.73% for 1, 3, and 5 years, respectively. The OS rate for 5 years was 40.28%. Independent risk factors for 1-year DFS were maximum tumor diameter >5 cm, age <49 years, and platelet transfusion. Independent risk factors for 3- and 5-year DFS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L. Independent risk factors for OS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L. ConclusionElevated FBG after LT for HCC may promote medium- to long-term tumor recurrence and affect OS. Age <49 years, platelet transfusion, maximum tumor diameter, capsular invasion, and microvascular invasion in patients with HCC also impact survival and tumor recurrence after LT.

Segmental Distribution of Hepatocellular Carcinoma Correlates with Microvascular Invasion in Liver Explants Undergoing Transplantation.

Introduction Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI. Methods A single center, retrospective chart review, including 98 HCC patients, aged 18 years and older who had liver transplantation in our institute between 2012 and 2017. We reviewed the radiological images of the HCC tumors, the pathological findings of the explanted livers, and the follow-up imaging after transplantation. Results 98 patients with the diagnosis of HCC underwent liver transplantation between 2012 and 2017. The mean age of the cohort was 63 ± 8.2. Males represented 75% and Caucasian race represented 75% of the cohort. The most common etiology of cirrhosis was chronic hepatitis C virus infection followed by alcohol abuse and nonalcoholic steatohepatitis (NASH) with percentages of 50%, 23%, and 10%, respectively. Microvascular invasion was found in 16% of the patients while PVT and the recurrence of HCC were found in 17% and 6 % of the cohort, respectively. MVI was found in 10 single HCC and 6 multifocal HCC. Right lobe HCC had more MVI when compared to the left and multilobar HCC, with percentages of 11%, 2%, and 3%, respectively. Localization of HCC in segment 8 was associated with the highest percentage of MVI when compared to all other segments. The risk of MVI in segment 8 HCC was 3.5 times higher than the risk from the other segments (p=0.002) while no vascular invasion was found in segments 1, 3, and 5. The risk of vascular invasion in untreated HCC is 3 times the risk in treated HCC (P=0.03). Conclusion Our data indicate that the risk of microvascular invasion is highest in tumors localized to segment 8. The size and number of HCC tumors were not associated with an increased risk of microvascular invasion.

Overexpression of miR-21 Is Associated With Recurrence in Patients With Hepatitis B Virus–Mediated Hepatocellular Carcinoma Undergoing Liver Transplantation

Liver transplantation (LT) is the best treatment option for hepatitis B virus (HBV)–mediated hepatocellular carcinoma (HCC). Nevertheless, recurrence is the most important issue after LT. The aims of the present study were to evaluate the relation of dysregulated expression of microRNAs (miRNAs) in recurrence formation in HBV-mediated HCC cases. A total of 42 HBV-mediated HCC patients were evaluated in this study.Among 21 miRNAs, the expression level of miR-106a and miR-21 were higher and miR-143 and miR145 were lower in patients with HCC compared with noncancerous liver tissues (P = .0388, P = .0214, P = .0321, and P = .002, respectively). Compared with nonrecurrent patients, the expression level of miR-21 was 3.54-fold higher and miR-145 was 2.42-fold lower in patients with recurrence during the 5-year follow-up (P = .004 and P = .032; respectively). In addition, according to multivariate Cox regression analysis, the overexpression of miR-21 was found to be a prognostic indicator in HBV-mediated HCC patients (P = .002).In conclusion, we show a significant association between high expression of miR-21 and recurrence in HBV-mediated HCC. Therefore, up-regulation of miR-21 could serve as a promising prognostic marker for HCC.

Effect of Donor Race-Matching on Overall Survival for African-American Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

Liver transplantation (LT) is the preferred treatment for early hepatocellular carcinoma (HCC) in select patients. Differences in outcomes after LT have been previously described between recipient races, but the role of donor race is not well defined. This study sought to examine the effect of donor-recipient race-matching on overall survival after liver transplantation for HCC in African-American patients (AA). Adult AA patients with HCC undergoing liver transplantation were identified using the Organ Procurement and Transplantation Network database (1994 to 2015). Recipient and donor demographic and clinical characteristics were collected. Patients were separated into unadjusted cohorts based on whether the liver donor was AA (matched) or another race (unmatched). The primary outcome was overall survival, which was analyzed by log-rank test and graphed using the Kaplan-Meier method. Multivariate regression modeling was used to determine adjusted hazard ratios (HR) for overall survival. Of 1,384 AA patients identified, 325 (23.5%) were race-matched. Matched patients experienced significantly better median overall survival when compared with the unmatched cohort (135 vs 78 months, p= 0.007). Multivariate analysis revealed an adjusted hazard ratio of 0.66 for race-matched transplantation (95% CI 0.49 to 0.88; p= 0.004). Matched patients also experienced an improved 5-year survival (64.2% vs 56.9%; p= 0.019). African-American HCC patients undergoing liver transplantation experienced significantly improved overall survival when the donor race matched the recipient race. Donor-recipient race-matching remained an independent predictor of improved survival after adjusting for comorbidities and disease characteristics. Race-matching should be considered in the process of organ allocation because it may affect long-term survival in African-American HCC patients.

Detection of Novel Fusion Transcript VTI1A-CFAP46 in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is now the second-highest cause of cancer death worldwide. Recent studies have discovered a wide range of somatic mutations in HCC. These mutations involve various vital signaling pathways such as: Wnt/β-Catenin, p53, telome­rase reverse transcriptase (TERT), chromatin remodeling, RAS/MAPK signaling, and oxidative stress. However, fusion transcripts have not been broadly explored in HCC. Methods: To identify novel fusion transcripts in HCC, in the first phase of our study, we performed targeted RNA sequencing (in HCC and paired non-HCC tissues) on 6 patients with a diagnosis of HCC undergoing liver transplantation. Results: As a result of these studies, we discovered the novel fusion transcript, VTI1A-CFAP46. In the second phase of our study, we measured the expression of wild-type VTI1A in 21 HCC specimens, which showed that 10 of 21 exhibited upregulation of wild-type VTI1A in their tumors. VTI1A (Vesicle Transport via Interaction with t-SNARE homolog 1A) is a member of the Soluble N-ethylmaleimide-Sensitive Factor (NSF) attachment protein receptor (SNARE) gene family, which is essential for membrane trafficking and function in endocytosis, autophagy, and Golgi transport. Notably, it is known that autophagy is involved in HCC. Conclusions: The link between novel fusion transcript VTI1A-CFAP46 and autophagy as a potential therapeutic target in HCC patients deserves further investigation. Moreover, this study shows that fusion transcripts are worthy of additional exploration in HCC.

Impact of Early Initiated Everolimus on the Recurrence of Hepatocellular Carcinoma After Liver Transplantation.

Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation. This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders. Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation. Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.

Association between expression of Cullin 4B and prognosis of patients after liver transplantation

Objective To investigate the effect of expression of Cullin 4B (CUL4B) on the prognosis of patients after liver transplantation for hepatocellular carcinoma (HCC). Methods The retrospective case-control study was conducted. The clinicopathological data of 79 patients who underwent liver transplantation for HCC in the First Affiliated Hospital of Sun Yat-sen University between January 1, 2014 and June 30, 2015 were collected. The specimens of HCC tissues were collected and embedded in paraffin, and then were detected by immunohistochemistry staining. Observation indicators: (1) expression of CUL4B in HCC tissues; (2) follow-up and survival; (3) prognostic factors analysis after liver transplantation; (4) association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation. Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis and survival up to June 2018. Measurement data with normal distribution were represented as ±s. The comparison between groups of count data was done using the chi-square test. The survival curve drawn using the Kaplan-Meier method, and the survival analysis was done by Log-rank test. The univariate and multivariate analysis were respectively done using the COX regression model. The association analysis was done using the Pearson test. Results (1) Expression of CUL4B in HCC tissues: immunohistochemistry staining showed that CUL4B was mainly expressed in the cytoplasm, with a powerful brownish-yellow staining. The high expression and low expression of CUL4B in HCC tissues were detected in 64 and 15 patients, respectively. (2) Follow-up and survival: 79 patients were followed up for 38-56 months, with an average time of 46 months. During the follow-up, 37 patients had no tumor recurrence and 42 had tumor recurrence (32 with tumor extrahepatic metastasis and 10 with intrahepatic metastasis); 36 had survival and 43 died; the 1- and 3-year overall survival rates were respectively 86.84% and 63.25%, and 1- and 3-year tumor-free survival rates were respectively 62.31% and 51.27%. (3) Prognostic factors analysis after liver transplantation: ① Results of univariate analysis showed that preoperative alpha-fetoprotein (AFP), Child-Pugh score, maximum tumour dimension, capsular invasion, intravascular tumor thrombus, Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Hazard Ratio (HR)=2.17, 3.36, 3.66, 2.43, 2.19, 3.36, 2.84, 95% confidence interval (CI): 1.17-4.04, 1.53-7.42, 2.10-6.42, 1.33-4.17, 1.08-9.04, 1.58-7.59, 1.17-6.32, P<0.05]. The preoperative alpha-fetoprotein (AFP), Child-Pugh score, maximum tumour dimension, capsular invasion, intravascular tumor thrombus, Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (HR=2.06, 3.72, 3.16, 2.36, 2.83, 3.21, 1.69, 95%CI: 1.34-4.85, 1.72-8.63, 1.79-7.31, 1.46-4.86, 1.19-8.63, 1.19-7.92, 1.06-4.87, P<0.05). ② Results of multivariate analysis showed that maximum tumour dimension, intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Odds ratio(OR)=3.43, 3.69, 2.81, 95%CI: 1.16-6.02, 1.96-9.38, 1.04-9.63, P<0.05]. The maximum tumour dimension, intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (OR=2.25, 4.72, 2.74, 95%CI: 1.16-4.02, 1.98-9.47, 1.03-7.10, P<0.05). The 3-year overall survival rate in patients with high- and low-expressions of CUL4B was respectively 66.7% and 32.8%, with a statistically significant difference (χ2=5.69, P<0.05). The 3-year tumor-free survival rate in patients with high- and low-expressions of CUL4B was respectively 73.3% and 18.6%, with a statistically significant difference (χ2=4.63, P<0.05). (4) Association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation: results of Pearson test showed that expression of CUL4B was significantly associated with HCC recurrence and metastasis after liver transplantation (r=0.62, P<0.05). The further analysis showed that expression of CUL4B was significantly associated with extrahepatic metastasis after liver transplantation (r=0.84, P<0.05). Conclusion The expression of CUL4B is associated with HCC recurrence after liver transplantation, and it can be as a predictor for HCC recurrence and distant metastasis after liver transplantation. Key words: Hepatic neoplasms; Liver transplantation; Cullin 4B; Recurrence; Metastasis; Prognosis

Propensity-Matched Analysis of Patients with Mixed Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation.

Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC-CCA and a matched cohort of HCC LT recipients. A retrospective, single-center analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha-fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC-CCA recipients trended toward inferior recurrence-free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC-CCA patients with well-moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence-free survival and are not inherently more aggressive tumors. Low-grade, well-moderately differentiated HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC-CCA may allow for successful utilization of LT in this subset of patients.

The effect of donor race-matching on overall survival for african american patients undergoing liver transplantation for hepatocellular carcinoma

Introduction: Liver transplantation (LT) is the preferred treatment for early hepatocellular carcinoma (HCC) in select patients. Differences in outcomes following LT has been previously described between recipient races, but the role of donor race is not well-defined. This study sought to examine the effect of donor-recipient race-matching on overall survival following liver transplantation for HCC in African Americans (AA). Methods: Adult AA patients with HCC undergoing liver transplantation were identified using the Organ Procurement and Transplantation Network database (1994-2015). Recipient and donor demographic and clinical characteristics were collected. Patients were separated into unadjusted cohorts based on whether the liver donor was AA (matched) or another race (unmatched). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine adjusted hazard ratios (HR) for OS. Results: Of 1,384 AA patients identified, 325 (23.5%) were race-matched. Matched patients experienced significantly better median overall survival compared to the unmatched cohort (135 vs. 78 months, p=0.007). Multivariate analysis revealed an adjusted hazard ratio of 0.66 for race-matched transplantation (95% CI: 0.49-0.88; p=0.004). Matched patients also experienced improved five-year survival (64.2% vs. 56.9%; p=0.019). Conclusion: African American HCC patients undergoing liver transplantation experienced significantly improved overall survival when the donor race matched the recipient race. Donor-recipient race-matching remained an independent predictor of improved survival after adjusting for comorbidities and disease characteristics. Race-matching should be considered in the process of organ allocation, as it may impact long-term survival in African Americans.

Application of a novel liquid biopsy in patients with hepatocellular carcinoma undergoing liver transplantation.

Circulating tumor cells (CTCs) serves a primary function in metastasis and recurrence of hepatocellular carcinoma (HCC). In the present study, in order to evaluate the analytical performance and clinical value of the liquid biopsy-based platform, a novel integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (iFISH®) platform was applied to analyze CTCs in patients with HCC undergoing liver transplantation (LT). In total, 30 patients with HCC undergoing LT and 10 healthy volunteers were enrolled. CTCs in peripheral blood that were obtained from each patient prior to LT and 3 months thereafter were detected using the iFISH® platform, and CellSearch® system was performed for each subject for comparison. Using iFISH® and CellSearch®, the percentage of CTCs in patients with pre-operative HCC were 70.00% and 26.67%, respectively. CTCs counted using iFISH® (iFISH-CTCs) were increased compared with CellSearch® (Cellsearch-CTCs) (P<0.01). A significant decrease in iFISH-CTCs was observed 3 months following LT (3.04±0.93/7.5 to 1.0±0.53/7.5 ml, P<0.05). Furthermore, patients with lower preoperative iFISH-CTCs level (<5/7.5 ml) had markedly increased recurrence-free survival compared with iFISH-CTCs (>5/7.5 ml, 15 vs. 5.5 months; P<0.01. iFISH® platform exhibits an increased analytical sensitivity, and may be used as a dynamic monitoring tool for CTCs, and CTCs may be a good prognostic indicator for patients with HCC undergoing LT.

Clinical, Epidemiological and Histopathological Aspects in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Background:Hepatocellular Carcinoma (HCC) is the primary liver cancer with high incidence and mortality rates. Currently one of the major etiologies for liver disease, HCC and liver transplantation is nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the epidemiological, histopathological and clinical aspects of HCC transplant patients, with emphasis on NAFLD etiology.Methods:This study included all HCC patients submitted to liver transplantation from 2010 to 2016 of the University Reference Center. The analyzed variables were age, gender, ethnicity, causes that led to liver transplantation, alpha-fetoprotein (AFP) dosage, histological aspects, recurrence, survival and NAFLD.Results:A total of 60 patients were included in the study being 80% men with a mean age of 58.3 ± 10.6 years. All patients were cirrhotic. The causes that led to the transplantation were the presence of the hepatitis C virus (HCV) (56.6% of the patients), an association of the virus with alcohol (20%), the presence of the hepatitis B virus (HBV) (20%), alcoholic liver disease (ALD) (50.9%) and NAFLD (25%). Of the latter, eight were diagnosed pre-transplantation and seven were NAFLD carriers without a previous diagnosis. Regarding the Edmondson-Steiner histological classification, 58.5% of the patients were classified as grade ≤ II.Conclusions:There is predominance of male patients with a mean age of 58.3 years. Degree ≤ II is the most frequent to the Edmondson-Steiner histological classification in the evaluated casuistic. HCV, ALD and NAFLD is the most common etiological agents found in the study. The (high) underestimated prevalence of NAFLD in the pre-transplanted patients is due to the fact that all patients presented cirrhosis, masking NAFLD signals.

Value of HCC-MELD Score in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation.

Liver transplantation (LT) is considered the ideal therapy for patients with hepatocellular carcinoma (HCC) having cirrhosis but the shortage of liver donors and the risk of dropout from the wait list due to tumor progression severely limit transplantation. A new prognostic score, the HCC-model for end-stage liver disease (HCC-MELD), was developed by combining α-fetoprotein (AFP), MELD, and tumor size, to improve risk stratification of dropout in patients with HCC. In this study, we investigated the ability of the HCC-MELD score in predicting the posttransplant for patients fulfilling Milan criteria (MC). Two hundred patients with stage II tumor were retrospectively reviewed from a total of 1290 transplants performed at our institution from October 1997 through April 2015. Cox regression analysis was performed to identify the prognostic factors impacting the posttransplant survival. Overall survival at 1, 5, and 10 years was 89.3%, 71.1%, and 67.2%, whereas disease-free survival was 86.4%, 66.5%, and 52.4%, respectively. Multivariate analysis showed HCC-MELD score (hazard ratio [HR] 39.6, P < .001) and microvascular invasion (HR 2.41, P = .002) to be independent risk factors for recurrence, whereas HCC diameter (HR 1.15, P = .041), HCC-MELD (HR 15.611, P = .006), and grading (HR 2.17, P = .03) proved to be predictive factors of poor overall survival. Our study showed the validity of the HCC-MELD equation in the evaluation of patients undergoing LT for HCC. This score offers a reliable method to assess the risk of waiting list dropout and predict posttransplantation outcomes.