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.

scholarly journals Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Raphael Iglesias de Oliveira Vidal ◽  
Edison Iglesias de Oliveira Vidal ◽  
Basilio de Bragança Pereira ◽  
Cachimo Combo Assane ◽  
Alexandre Ribeiro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Regression Model ◽  
Cox Regression ◽  
Microvascular Invasion ◽  
University Hospital ◽  
Explanted Liver ◽  
Hcc Recurrence

Purpose. We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). Methods. This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. Results. Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603 ), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190 ), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006 ), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001 ). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001 ). Conclusion. In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.

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 5-year Recurrence Prediction After Hepatocellular Carcinoma Resection Using Deep Learning and Cox Regression Models: A Large Prospective Study

2021 ◽  
Author(s):  
Hon-Yi Shi ◽  
King-The Lee ◽  
Chong-Chi Chiu ◽  
Jhi-Joung Wang ◽  
Ding-Ping Sun ◽  
...  
Keyword(s):  
Neural Network ◽  
Hepatocellular Carcinoma ◽  
Deep Learning ◽  
Surgical Resection ◽  
Scale Score ◽  
Cox Regression ◽  
Recurrence Prediction ◽  
Feature Importance ◽  
Importance Analysis ◽  
Hcc Recurrence

Abstract BackgroundRisk of hepatocellular carcinoma (HCC) recurrence after surgical resection is unknown. Therefore, the aim of this study was 5-year recurrence prediction after HCC resection using deep learning and Cox regression models.MethodsThis study recruited 520 HCC patients who had undergone surgical resection at three medical centers in southern Taiwan between April, 2011, and December, 2015. Two popular deep learning algorithms: a deep neural network (DNN) model and a recurrent neural network (RNN) model and a Cox proportional hazard (CPH) regression model were designed to solve both classification problems and regression problems in predicting HCC recurrence. A feature importance analysis was also performed to identify confounding factors in the prediction of HCC recurrence in patients who had undergone resection.ResultsAll performance indices for the DNN model were significantly higher than those for the RNN model and the traditional CPH model (p<0.001). The most important confounding factor in 5-year recurrence after HCC resection was surgeon volume followed by, in order of importance, hospital volume, preoperative Beck Depression Scale score, preoperative Beck Anxiety Scale score, co-residence with family, tumor stage, and tumor size. ConclusionsThe DNN model is useful for early baseline prediction of 5-year recurrence after HCC resection. Its prediction accuracy can be improved by further training with temporal data collected from treated patients. The feature importance analysis performed in this study to investigate model interpretability provided important insights into the potential use of deep learning models for predicting recurrence after HCC resection and for identifying predictors of recurrence.

scholarly journals Factors influencing early recurrence of hepatocellular carcinoma after curative resection

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094555
Author(s):  
Yu Zhu ◽  
Lingling Gu ◽  
Ting Chen ◽  
Guoqun Zheng ◽  
Chao Ye ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Curative Resection ◽  
Cox Regression ◽  
Postoperative Recurrence ◽  
Early Recurrence ◽  
Tumor Diameter ◽  
Cox Regression Analysis ◽  
Factors Influencing ◽  
Linear Manner ◽  
Hcc Recurrence

Objective To identify the factors influencing early recurrence in patients with hepatocellular carcinoma (HCC) after curative resection. Methods Clinical data for 99 patients with HCC undergoing curative resection were analyzed. The clinicopathological factors influencing early recurrence were analyzed by Cox regression. Results Twenty-five of 99 patients (25.3%) suffered from early recurrence. There were significant differences between patients with and without recurrence in terms of tumor diameter, tumor capsular integrity, and preoperative alpha fetoprotein level. Cox regression analysis revealed that a tumor diameter >2.6 cm and preoperatively increased total bilirubin (TBL) level were risk factors for postoperative recurrence, while tumor capsular integrity had a protective effect on postoperative recurrence. After adjusting for preoperative TBL level and tumor capsular integrity, the risk of HCC recurrence was markedly increased in line with increasing tumor diameter in a non-linear manner. Conclusion Tumor diameter >2.6 cm and preoperatively increased TBL level are associated with a higher risk of early recurrence after curative resection in patients with HCC, while tumor capsular integrity is associated with a lower risk of early recurrence.

scholarly journals Long-Term Outcomes and Evaluation of Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Eradication by Direct-Acting Antiviral Treatment: All Kagawa Liver Disease Group (AKLDG) Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2257
Author(s):  
Joji Tani ◽  
Tomonori Senoh ◽  
Akio Moriya ◽  
Chikara Ogawa ◽  
Akihiro Deguchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Treatment ◽  
Survival Rates ◽  
Long Term Outcomes ◽  
Recurrence Rates ◽  
Virus Eradication ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Hcc Recurrence

There are limited studies that have evaluated the long-term outcomes in patients with hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment. In this retrospective study, we aimed to investigate the recurrence rates, recurrence factors, and prognosis of 130 patients who were treated with IFN-free DAA treatment after treatment for HCC. The median observation time was 41 ± 13.9 months after DAA treatment. The recurrence rates of HCC were 23.2%, 32.5%, 46.3%, and 59.4% at 6, 12, 24, and 36 months, respectively. A multivariate analysis showed that palliative treatment prior to DAA treatment (HR = 3.974, 95% CI 1.924–8.207, p = 0.0006) and alpha-fetoprotein at sustained virological response 12 (HR = 1.048, 95% CI 1.016–1.077, p = 0.0046) were associated with independent factors for HCC recurrence (HCC-R). The 12-, 24-, and 36-month overall survival rates were 97.6%, 94.0%, and 89.8%, respectively. The 12-, 24-, and 36-month survival rates of the non-recurrence and recurrence groups were 97.7%, 97.7%, and 94.1% and 97.6%, 92.3%, and 87.9%, respectively (p = 0.3404). The size of the main tumor lesion and the serological data were significantly improved at the time of HCC-R after DAA treatment. This study showed an improved prognosis regardless of recurrence rate, which suggests that DAA treatment in HCV patients should be considered.

scholarly journals Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients

2020 ◽  
Vol 26 (4) ◽  
pp. 516-528
Author(s):  
Jihye Kim ◽  
Wonseok Kang ◽  
Dong Hyun Sinn ◽  
Geum-Youn Gwak ◽  
Yong-Han Paik ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Recurrence Rate ◽  
Early Stage ◽  
Cancer Staging ◽  
High Recurrence Rate ◽  
Recurrence Rates ◽  
Substantial Risk ◽  
Hcc Recurrence

Background/Aims: Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.Methods: A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed.Results: During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years.Conclusions: The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

scholarly journals Role of Allelic Imbalance in Predicting Hepatocellular Carcinoma (HCC) Recurrence Risk After Liver Transplant

2019 ◽  
Vol 24 ◽  
pp. 223-233 ◽  
Author(s):  
Duilio Pagano ◽  
Floriana Barbera ◽  
Pier Giulio Conaldi ◽  
Aurelio Seidita ◽  
Fabrizio Di Francesco ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Allelic Imbalance ◽  
Recurrence Risk ◽  
Hcc Recurrence

Recurrence of hepatocellular carcinoma after liver transplantation: Comparison between superselective and non-superselective chemoembolization.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 238-238
Author(s):  
Andrew Smith ◽  
Michael Heckman ◽  
Daniel Serie ◽  
Denise M Harnois ◽  
Justin H. Nguyen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Necrosis ◽  
Multivariable Analysis ◽  
Tumor Stage ◽  
Meld Score ◽  
Recurrence Rates ◽  
Exact Test ◽  
Risk Of Death ◽  
Strong Trend ◽  
Hcc Recurrence

238 Background: To compare post-transplant recurrence rates of hepatocellular carcinoma (HCC) and differences in percent tumor necrosis in patients with pre-operative superselective chemoembolization (CE) vs. non-superselective CE. Methods: Retrospective review of 147 patients with liver transplant (LT) for HCC treated with pre-operative CE. Those transplanted less than 24 hours after CE and those who had other concomitant treatments were excluded. The angiographic studies and written reports were reviewed to categorize patients into superselective and non-superselective groups. CE was done with an emulsion of lipiodol, cisplatin, doxorubicin, mitomycin C, and contrast, with or without embolization particles. Superselective CE was defined as treatment directly into the vessel(s) feeding the tumor. Treatment from more proximal vessels was considered non-superselective. Data gathered included age, gender, date of CE, date of LT, tumor size and number, tumor stage, MELD score, Child-Pugh class, alpha fetoprotein, percent tumor necrosis at explant, date of recurrence, date and cause of death, and date of last follow-up. Patient and disease characteristics and percent tumor necrosis were analyzed with a Wilcoxon rank sum test or Fisher’s exact test. The Kaplan-Meier method was used to estimate the cumulative incidences of death due to recurrent disease after LT. Results: 99 patients were included, 53 had superselective CE and 46 non-superselective. HCC recurrence rates at 1, 3, 5, and 8 years were all significantly less for superselective CE compared to non-superselective CE (p = 0.039 single, p = 0.011 multivariable). Using multivariable analysis, superselective CE had a lower risk of death due to recurrent HCC at 1, 3, 5, and 8 years (p = 0.046). There was a trend toward more percent tumor necrosis after superselective CE, but it did not reach significance (p = 0.057). Conclusions: This study provides evidence that HCC recurrence after LT and death due to recurrent HCC is lower after pre-LT superselective CE versus non-superselective CE. The strong trend for greater percent tumor necrosis with superselective CE may explain the differences in recurrence rate.

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.

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