scholarly journals A Meta-Analysis on the Rate of Hepatocellular Carcinoma Recurrence after Liver Transplant and Associations to Etiology, Alpha-Fetoprotein, Income and Ethnicity

2021 ◽  
Vol 10 (2) ◽  
pp. 238
Author(s):  
Darren J. H. Tan ◽  
Chloe Wong ◽  
Cheng Han Ng ◽  
Chen Wei Poh ◽  
Sneha Rajiv Jain ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Latin American ◽  
Economic Status ◽  
Meta Analysis ◽  
Deceased Donor ◽  
Alpha Fetoprotein ◽  
Milan Criteria ◽  
Asian Populations ◽  
Hcc Recurrence

Hepatocellular carcinoma (HCC) recurrence after liver transplant is associated with a poor prognosis and significantly increases morbidity and mortality among liver transplant patients. Therefore, this meta-analysis aims to evaluate the overall prevalence of HCC recurrence following liver transplant. Medline and Embase databases were searched, and a meta-analysis of proportions was conducted. Observational studies reporting the prevalence of recurrent hepatocellular carcinoma (HCC) after liver transplant were included, with the analysis being stratified by adherence to Milan criteria, ethnicity, socio-economic status, alpha fetoprotein (AFP) levels, living donor vs. deceased donor, and the underlying aetiology of the liver disease. A meta-regression on the date of the study completion was also performed. Of a total 40,495 patients, 3888 developed an HCC recurrence. The overall prevalence of recurrent HCC was 13% (CI: 0.12–0.15). Patients beyond the Milan criteria (MC) were more likely to recur than patients within MC. Asian populations had the greatest prevalence of HCC recurrence (19%; CI: 0.15–0.24) when compared to Western (12%; CI: 0.11–0.13) and Latin American populations (11%; CI: 0.09–0.14). The prevalence of recurrent HCC was the highest in patients infected with hepatitis B virus (HBV) (18%; CI: 0.11–0.27) compared to other aetiologies. A higher AFP also resulted in an increased recurrence. This highlights interesting differences based on ethnicity, income, and aetiology, and further studies are needed to determine the reasons for the disparity.

Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the Milan Criteria: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 152 (5) ◽  
pp. S1124
Author(s):  
Thapanakul Emyoo ◽  
Piyapon Utako ◽  
Noriyo Yamashiki ◽  
Thunyarat Anothaisintawee ◽  
Ammarin Thakkinstian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Liver Transplantation ◽  
Meta Analysis ◽  
Milan Criteria

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.

scholarly journals HEPATOCELLULAR CARCINOMA PATIENTS ARE ADVANTAGED IN THE CURRENT BRAZILIAN LIVER TRANSPLANT ALLOCATION SYSTEM. A COMPETING RISK ANALYSIS

2020 ◽  
Vol 57 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Santiago RODRÍGUEZ ◽  
Alfeu de Medeiros FLECK JR ◽  
Marcos MUCENIC ◽  
Cláudio MARRONI ◽  
Ajacio BRANDÃO
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Risk Model ◽  
Rio Grande ◽  
Deceased Donor ◽  
Meld Score ◽  
Waiting List ◽  
Competing Risk ◽  
Rio Grande Do Sul ◽  
Donor Liver Transplantation

ABSTRACT BACKGROUND: In Brazil, the Model for End-Stage Liver Disease (MELD) score is used to prioritize patients for deceased donor liver transplantation (DDLT). Patients with hepatocellular carcinoma (HCC) receive standardized MELD exception points to account for their cancer risk of mortality, which is not reflected by their MELD score. OBJECTIVE: To compare DDLT rates between patients with and without HCC in Rio Grande do Sul, the Southernmost state of Brazil. METHODS - We retrospectively studied 825 patients on the liver-transplant waiting list from January 1, 2007, to December 31, 2016, in a transplant center located in Porto Alegre, the capital of Rio Grande do Sul, to compare DDLT rates between those with and without HCC. The time-varying hazard of waiting list/DDLT was estimated, reporting the subhazard ratio (SHR) of waiting list/DDLT/dropout with 95% confidence intervals (CI). The final competing risk model was adjusted for age, MELD score, exception points, and ABO group. RESULTS: Patients with HCC underwent a transplant almost three times faster than patients with a calculated MELD score (SHR 2.64; 95% CI 2.10-3.31; P<0.001). The DDLT rate per 100 person-months was 11.86 for HCC patients vs 3.38 for non-HCC patients. The median time on the waiting list was 5.6 months for patients with HCC and 25 months for patients without HCC. CONCLUSION: Our results demonstrated that, in our center, patients on the waiting list with HCC have a clear advantage over candidates listed with a calculated MELD score.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323663
Author(s):  
Victor Sapena ◽  
Marco Enea ◽  
Ferran Torres ◽  
Ciro Celsa ◽  
Jose Rios ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Recurrence Risk ◽  
Patient Data ◽  
Death Risk ◽  
Significant Difference ◽  
Direct Acting ◽  
Hcc Recurrence

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).ConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

Hepatocellular Carcinoma Occurrence/Recurrence after Direct-Acting Antivirals for Hepatitis C in Egyptian Cohort: Single-Center Experience

2019 ◽  
Vol 37 (6) ◽  
pp. 488-497
Author(s):  
Sameh A. Lashen ◽  
Mohammed M. Shamseya ◽  
Marwa A. Madkour
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
De Novo ◽  
Independent Predictor ◽  
Alpha Fetoprotein ◽  
Direct Acting Antivirals ◽  
Single Center ◽  
Single Center Experience ◽  
Direct Acting ◽  
Hcc Recurrence

Background: Conflicting data have been published about the risk of hepatocellular carcinoma (HCC) following direct-acting antivirals (DAAs). We investigated the incidence of HCC occurrence/recurrence after DAAs therapy. Patients and Methods: Retrospectively, we analyzed data of 392 patients with F3–4 fibrosis and cirrhosis treated by DAAs during the period from August 2015 to May 2018. In HCC-experienced patients, HCC treatment modality, and the duration between HCC management and DAAs initiation were recorded. In all patients, pretreatment clinicolaboratory evaluation, and imaging before, during and after DAAs were done. Results: De novo HCC occurred in 7.6% of naïve patients, while recurrence appeared in 28% of patients with previous HCC. Pretreatment alpha-fetoprotein was an independent predictor of HCC occurrence, while the time between HCC ablation and the beginning of DAAs was the only predictor of HCC recurrence (p < 0.001). Half of the patients who started DAAs before 6 months had HCC recurrence, while patients who started DAAs at ≥6 months had no recurrence (p< 0.0001). Conclusions: Although HCC occurrence after DAAs was not high, recurrence was apparently high. Pretreatment alpha-fetoprotein is a predictor for de novo HCC. The time between HCC ablation and DAAs was the strongest predictor of recurrence.

scholarly journals mTOR Expression in Liver Transplant Candidates with Hepatocellular Carcinoma: Impact on Histological Features and Tumour Recurrence

2019 ◽  
Vol 20 (2) ◽  
pp. 336 ◽  
Author(s):  
Marta Guerrero ◽  
Gustavo Ferrín ◽  
Manuel Rodríguez-Perálvarez ◽  
Sandra González-Rubio ◽  
Marina Sánchez-Frías ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Cox Regression ◽  
Cell Signalling ◽  
Mtor Pathway ◽  
Tumour Recurrence ◽  
Recurrence Rates ◽  
Explanted Liver ◽  
Peritumoral Tissue ◽  
Hcc Recurrence

(1) Background: The mammalian target of rapamycin (mTOR) pathway activation is critical for hepatocellular carcinoma (HCC) progression. We aimed to evaluate the mTOR tissue expression in liver transplant (LT) patients and to analyse its influence on post-LT outcomes. (2) Methods: Prospective study including a cohort of HCC patients who underwent LT (2012–2015). MTOR pathway expression was evaluated in the explanted liver by using the “PathScan Intracellular Signalling Array Kit” (Cell Signalling). Kaplan-Meier and Cox regression analyses were performed to evaluate post-LT HCC recurrence. (3) Results: Forty-nine patients were included (average age 56.4 ± 6, 14.3% females). Phospho-mTOR (Ser2448) was over-expressed in peritumoral tissue as compared with tumoral tissue (ΔSignal 22.2%; p < 0.001). The mTOR activators were also increased in peritumoral tissue (phospho-Akt (Thr308) ΔSignal 18.2%, p = 0.004; phospho-AMPKa (Thr172) ΔSignal 56.3%, p < 0.001), as they were the downstream effectors responsible for cell growth/survival (phospho-p70S6K (Thr389) ΔSignal 33.3%, p < 0.001 and phospho-S6RP (Ser235/236) ΔSignal 54.6%, p < 0.001). MTOR expression was increased in patients with multinodular HCC (tumoral p = 0.01; peritumoral p = 0.001). Increased phospho-mTOR in tumoral tissue was associated with higher HCC recurrence rates after LT (23.8% vs. 5.9% at 24 months, p = 0.04). (4) Conclusion: mTOR pathway is over-expressed in patients with multinodular HCC and is it associated with increased post-LT tumour recurrence rates.

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