scholarly journals Liver transplantation for hepatocellular carcinoma using grafts from uncontrolled circulatory death donation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anisa Nutu ◽  
Iago Justo ◽  
Alberto Marcacuzco ◽  
Óscar Caso ◽  
Alejandro Manrique ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Graft Survival ◽  
Patient Survival ◽  
Recurrence Rates ◽  
Similar Patient ◽  
Serum Alpha Fetoprotein ◽  
Recipient Age ◽  
Hcc Recurrence ◽  
Circulatory Death

AbstractControversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD). The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n = 103) with recipients of uncontrolled DCD livers (uDCD; n = 41). No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p = 0.040). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p = 0.031), pre-OLT bridging therapy (p = 0.024), and HCC recurrence (p = 0.048) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p = 0.045) as the single risk factor for HCC recurrence. In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to a shorter waitlist time, and lower waitlist dropout and HCC recurrence rates.

scholarly journals “Liver Transplantation for Hepatocellular Carcinoma using Grafts from Uncontrolled Circulatory Death Donation Versus Brain Death Donation” 

2021 ◽  
Author(s):  
Anisa Nutu ◽  
Iago Justo ◽  
Alberto Marcacuzco ◽  
Óscar Caso ◽  
Alejandro Manrique ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Brain Death ◽  
Graft Survival ◽  
Patient Survival ◽  
Similar Patient ◽  
Serum Alpha Fetoprotein ◽  
Recipient Age ◽  
Hcc Recurrence ◽  
Circulatory Death

Abstract Controversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD). The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n=103) with recipients of uncontrolled DCD livers (uDCD; n=41). No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p=0.04). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p=0.03), pre-OLT bridging therapy (p=0.02), and HCC recurrence (p=0.04) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p=0.04) as the single risk factor for HCC recurrence. In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to shorter waitlist time and similar HCC recurrence in both groups.

scholarly journals Liver Grafts with Major Extended Donor Criteria May Expand the Organ Pool for Patients with Hepatocellular Carcinoma

2019 ◽  
Vol 8 (10) ◽  
pp. 1692 ◽  
Author(s):  
Vladimir Lozanovski ◽  
Larissa Kerr ◽  
Elias Khajeh ◽  
Omid Ghamarnejad ◽  
Jan Pfeiffenberger ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Graft Survival ◽  
Patient Survival ◽  
Laboratory Model ◽  
Transplant Patients ◽  
One Year ◽  
End Stage ◽  
Donor Criteria ◽  
Extended Donor Criteria

The major extended donor criteria (maEDC; steatosis >40%, age >65 years, and cold ischemia time >14 h) influence graft and patient outcomes after liver transplantation. Despite organ shortages, maEDC organs are often considered unsuitable for transplantation. We investigated the outcomes of maEDC organ liver transplantation in patients with hepatocellular carcinoma (HCC). Two hundred and sixty-four HCC liver transplant patients were eligible for analysis. Risk factor analysis was performed for early allograft dysfunction; primary nonfunction; 30-day and 90-day graft failure; and 30-day, 90-day, and 1-year patient mortality. One-year graft survival was higher in recipients of no-maEDC grafts. One-year patient survival did not differ between the recipients of no-maEDC and maEDC organs. The univariate and multivariate analyses revealed no association between maEDC grafts and one-year patient mortality. Graft survival differed between the recipients of no-maEDC and maEDC organs after correcting for a laboratory model of end-stage liver disease (labMELD) score with a cut-off value of 20, but patient survival did not. Patient survival did not differ between recipients who did and did not meet the Milan criteria and who received grafts with and without maEDC. Instead of being discarded, maEDC grafts may expand the organ pool for patients with HCC without impairing patient survival or recurrence-free survival.

scholarly journals Cross-Match as an Immuno-Oncological Risk Factor for Hepatocellular Carcinoma Recurrence and Inferior Survival After Living Donor Liver Transplantation: A Call for Further Investigation

2020 ◽  
Vol 14 ◽  
pp. 117955492096877
Author(s):  
Cheng-Maw Ho ◽  
Rey-Heng Hu ◽  
Yao-Ming Wu ◽  
Ming-Chih Ho ◽  
Po-Huang Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Living Donor ◽  
Large Scale ◽  
Patient Survival ◽  
Multivariable Analysis ◽  
Donor Liver ◽  
Donor Liver Transplantation ◽  
Cross Match ◽  
Hcc Recurrence

Background: The success of immunotherapy for patients with hepatocellular carcinoma (HCC) suggests that immune dysregulation occurs in HCC patients. This warrants an immuno-oncological risk assessment in the platform of liver transplantation. Methods: This retrospective single-center study analyzed risk factors for—particularly cross-matching performed through conventional complement-dependent cytotoxicity cross-match tests—and the outcomes of HCC recurrence following living donor liver transplant. Results: A total of 71 patients were included. The median follow-up period was 29.1 months; 17 (23.9%) patients had posttransplant HCC recurrence, and their 1-, 3-, and 5-year-survival rates were 70.6%, 25.7%, and 17.1%, respectively, which were inferior to those of patients without HCC recurrence (87.0%, 80.7%, and 77.2%, respectively; P < .001). In addition to microvascular invasion, positive cross-match results for B cells at 37°C (B- 37°C) or T cells at 4°C (T- 4°C) were associated with inferior overall survival in multivariable analysis after adjustment for tumor status beyond Milan criteria and elevated alpha-fetoprotein levels. Rejection alone cannot be the mechanism underlying the effects of positive cross-match results on patient outcomes. Adjusted survival curves suggested that positive cross-match B- 37°C or T- 4°C was associated with inferior recurrence-free and patient survival, but the robustness of the finding was limited by insufficient power. Conclusions: Additional large-scale studies are required to validate positive cross-match as an immuno-oncological factor associated with HCC recurrence and inferior patient survival.

Role of Alpha-Fetoprotein in Selection of Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation: Must we Reconsider it?

2011 ◽  
Vol 26 (3) ◽  
pp. 153-159 ◽  
Author(s):  
Quirino Lai ◽  
Alfonso W. Avolio ◽  
Tommaso M. Manzia ◽  
Salvatore Agnes ◽  
Giuseppe Tisone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Multivariate Logistic Regression Analysis ◽  
Alpha Fetoprotein ◽  
Rank Test ◽  
Recurrence Prediction ◽  
Serum Alpha Fetoprotein ◽  
Selection Of Patients ◽  
Hcc Recurrence ◽  
Selection Of

Background Milan criteria (MC) represent the most commonly adopted criteria for the selection of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, MC are exclusively based on morphological aspects. The aim of the present study was to evaluate pre-LT–detectable biological parameters, to compare them with morphological ones in terms of tumor recurrence prediction and patient survival. Methods A cohort of 153 consecutive adult patients who underwent LT for HCC on cirrhosis from January 1999 to March 2009 was retrospectively analyzed. Results HCC recurrence was observed in 12 patients (7.8%). At multivariate logistic regression analysis, serum alpha-fetoprotein (AFP) was the unique independent negative risk factor for the development of HCC recurrence (odds ratio 2.0, p=0.03). Adopting a cutoff value of 210 ng/mL, patients who presented serum AFP ≥210 ng/mL showed a 5-year survival rate of 23.3% versus 76.2% observed in patients with pre-LT serum AFP <210 ng/mL (log-rank test: <0.0001). Conclusions In our experience, AFP was the strongest predictor of HCC recurrence, stronger than tumor morphology. AFP could ameliorate the selection of LT candidates. Further studies to evaluate the combination of morphological and biological criteria are needed.

scholarly journals Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2499
Author(s):  
Lisanne Noordam ◽  
Zhouhong Ge ◽  
Hadiye Özturk ◽  
Michail Doukas ◽  
Shanta Mancham ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Occult Metastasis ◽  
Recurrence Rates ◽  
Curative Intent ◽  
Cancer Testis Antigens ◽  
Negative Prognostic Factor ◽  
Increased Risk ◽  
Hcc Recurrence ◽  
Cancer Testis

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

scholarly journals Tailored Prediction Model of Survival after Liver Transplantation for Hepatocellular Carcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2869
Author(s):  
Indah Jamtani ◽  
Kwang-Woong Lee ◽  
Yun-Hee Choi ◽  
Young-Rok Choi ◽  
Jeong-Moo Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Prediction Model ◽  
Risk Group ◽  
Significant Risk ◽  
Risk Scores ◽  
Accurate Information ◽  
Survival Prediction ◽  
Good Prediction ◽  
Recurrence Rates

This study aimed to create a tailored prediction model of hepatocellular carcinoma (HCC)-specific survival after transplantation based on pre-transplant parameters. Data collected from June 2006 to July 2018 were used as a derivation dataset and analyzed to create an HCC-specific survival prediction model by combining significant risk factors. Separate data were collected from January 2014 to June 2018 for validation. The prediction model was validated internally and externally. The data were divided into three groups based on risk scores derived from the hazard ratio. A combination of patient demographic, laboratory, radiological data, and tumor-specific characteristics that showed a good prediction of HCC-specific death at a specific time (t) were chosen. Internal and external validations with Uno’s C-index were 0.79 and 0.75 (95% confidence interval (CI) 0.65–0.86), respectively. The predicted survival after liver transplantation for HCC (SALT) at a time “t” was calculated using the formula: [1 − (HCC-specific death(t’))] × 100. The 5-year HCC-specific death and recurrence rates in the low-risk group were 2% and 5%; the intermediate-risk group was 12% and 14%, and in the high-risk group were 71% and 82%. Our HCC-specific survival predictor named “SALT calculator” could provide accurate information about expected survival tailored for patients undergoing transplantation for HCC.

Kidney transplantation in the extremely elderly from extremely aged deceased donors: a kidney for each age

2020 ◽  
Vol 35 (4) ◽  
pp. 687-696
Author(s):  
Jimena Cabrera ◽  
Mario Fernández-Ruiz ◽  
Hernando Trujillo ◽  
Esther González ◽  
María Molina ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Cox Regression ◽  
Patient Survival ◽  
Incidence Rates ◽  
Allocation Policy ◽  
Recipient Age ◽  
Deceased Donors ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Advances in life expectancy have led to an increase in the number of elderly people with end-stage renal disease (ESRD). Scarce information is available on the outcomes of kidney transplantation (KT) in extremely elderly patients based on an allocation policy prioritizing donor–recipient age matching. Methods We included recipients ≥75 years that underwent KT from similarly aged deceased donors at our institution between 2002 and 2015. Determinants of death-censored graft and patient survival were assessed by Cox regression. Results We included 138 recipients with a median follow-up of 38.8 months. Median (interquartile range) age of recipients and donors was 77.5 (76.3–79.7) and 77.0 years (74.7–79.0), with 22.5% of donors ≥80 years. Primary graft non-function occurred in 8.0% (11/138) of patients. Cumulative incidence rates for post-transplant infection and biopsy-proven acute rejection (BPAR) were 70.3% (97/138) and 15.2% (21/138), respectively. One- and 5-year patient survival were 82.1 and 60.1%, respectively, whereas the corresponding rates for death-censored graft survival were 95.6 and 93.1%. Infection was the leading cause of death (46.0% of fatal cases). The occurrence of BPAR was associated with lower 1-year patient survival [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.64–10.82; P = 0.003]. Diabetic nephropathy was the only factor predicting 5-year death-censored graft survival (HR = 4.82, 95% CI 1.08–21.56; P = 0.040). Conclusions ESRD patients ≥75 years can access KT and remain dialysis free for their remaining lifespan by using grafts from extremely aged deceased donors, yielding encouraging results in terms of recipient and graft survival.

scholarly journals Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Walid El Moghazy ◽  
Samy Kashkoush ◽  
Glenda Meeberg ◽  
Norman Kneteman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Tumor Recurrence ◽  
Patient Survival ◽  
Steady Increase ◽  
Liver Transplants ◽  
Significant Difference ◽  
One Year ◽  
Over Time

Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants.Methods.We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma.Results.Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P<0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P=0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P=0.016).Conclusions.iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC.

scholarly journals Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mamatha Bhat ◽  
Sergi Clotet-Freixas ◽  
Cristina Baciu ◽  
Elisa Pasini ◽  
Ahmed Hammad ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Protein Expression ◽  
Univariate Analysis ◽  
Milan Criteria ◽  
Post Transplant ◽  
Gene And Protein Expression ◽  
Galectin 3 ◽  
Transcriptomic Signature ◽  
Hcc Recurrence

Abstract Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples. Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.

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