Laparoscopic Resection of Recurrence from Hepatocellular Carcinoma after Liver Transplantation: Case Reports and Review of the Literature

Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) indicates a poor prognosis. Surgery is considered the only curative option for selected patients with HCC recurrence following LT. Traditionally, the preference is given to the open approach.Methods. In this report, we present two cases of laparoscopic resections (LR) for recurrent HCC after LT, performed at Oslo University Hospital, Rikshospitalet.Results. Both procedures were executed without intraoperative and postoperative adverse events. Whereas one of the patients had a recurrence one year after LR, the other patient did not have any sign of disease during 3-year follow-up.Conclusions. We argue that, in selected cases, patients with HCC recurrence following LT may benefit from LR due to its limited tissue trauma and timely start of subsequent treatment if curative resection cannot be obtained. In patients with relatively favorable prognosis, LR facilitates postoperative recovery course and avoids unnecessary laparotomy.

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

BioMed Research International ◽

10.1155/2020/1487593 ◽

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.

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

Journal of Transplantation ◽

10.1155/2016/1916387 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 1

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.

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

Clinical Proteomics ◽

10.1186/s12014-021-09333-x ◽

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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Low Serum Melatonin Levels Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma are Associated with Lower Survival after Liver Transplantation

International Journal of Molecular Sciences ◽

10.3390/ijms20071696 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1696

Author(s):

Leonardo Lorente ◽

Sergio Rodriguez ◽

Pablo Sanz ◽

Pedro Abreu-González ◽

Agustín González-Rivero ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Antioxidant Capacity ◽

Total Antioxidant Capacity ◽

Serum Levels ◽

High Serum ◽

Published Data ◽

Lower Serum ◽

Total Antioxidant ◽

One Year

Melatonin administration has been associated with different benefits in animals and patients suffering from liver diseases. However, there is no published data about circulating melatonin levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Thus, the objective of this observational and retrospective study was to determine whether patients with HCC with lower serum melatonin levels prior to LT have a higher risk of one-year mortality after LT. We measured serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity (to assess antioxidant state) before LT. One-year surviving LT patients (n = 129) showed higher serum levels of melatonin (p = 0.001) and total antioxidant capacity (p = 0.001) and lower serum levels of malondialheyde (p = 0.01) than non-surviving LT patients (n = 16). Logistic regression analysis showed that high serum melatonin levels prior to LT were associated with lower one-year LT mortality (odds ratio = 0.525; 95% confidence interval (CI) = 0.331–0.834; p = 0.006). We found an association between serum levels of melatonin with serum levels of malondialheyde (rho = −0.22; p = 0.01) and total antioxidant capacity (rho = 0.21; p = 0.01). Thus, the novel findings of our study were the association between high serum melatonin levels prior to LT and survival at first year after LT and the association between serum levels of melatonin with malondialheyde and total antioxidant capacity.

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Role of Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation

Progress in Transplantation ◽

10.1177/1526924816664083 ◽

2016 ◽

Vol 26 (4) ◽

pp. 348-355 ◽

Cited By ~ 13

Author(s):

Nicola de’Angelis ◽

Filippo Landi ◽

Marco Nencioni ◽

Anais Palen ◽

Eylon Lahat ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Survival Rates ◽

Early Recurrence ◽

Best Supportive Care ◽

Curative Intent ◽

Sorafenib Group ◽

Hepatocellular Carcinoma Recurrence ◽

Retrospective Comparative Study ◽

Hcc Recurrence

Context: The management of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is challenging, especially if it is not treatable by surgery or embolization. Objectives: The present study aims to compare the survival rates of liver transplanted patients receiving sorafenib or best supportive care (BSC) for HCC recurrence not amenable to curative intent treatments. Design: This is a retrospective comparative study on a prospectively maintained database. Participants: Liver transplanted patients with untreatable HCC recurrence receiving BSC (n = 18) until 2007 or sorafenib (n = 15) thereafter were compared. Results: No group difference was observed for demographic characteristics at the time of transplantation and at the time of HCC recurrence. On the explant pathology of the native liver, 81.2% patients were classified within the Milan criteria, and 53.1% presented with microvascular invasion. Hepatocellular carcinoma recurrence was diagnosed 17.8 months (standard deviation: 14.5) after LT, with 17 (53.1%) patients presenting with early recurrence (≤12 months). The 1-year survival from untreatable progression of HCC recurrence was 23.9% for the BSC and 60% for the sorafenib group ( P = .002). The type of treatment (sorafenib vs BSC) was the sole independent predictor of survival (hazard ratio: 2.98; 95% confidence interval: 1.09-8.1; P = .033). In the sorafenib group, 8 (53.3%) patients required dose reduction, and 2 (13.3%) patients discontinued the treatment due to intolerable side effects. Conclusion: Sorafenib improves survival and is superior to the BSC in cases of untreatable posttransplant hepatocellular carcinoma recurrence.

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Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms17091524 ◽

2016 ◽

Vol 17 (9) ◽

pp. 1524 ◽

Cited By ~ 10

Author(s):

Leonardo Lorente ◽

Sergio Rodriguez ◽

Pablo Sanz ◽

Antonia Pérez-Cejas ◽

Javier Padilla ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Prognostic Value ◽

Cytokeratin 18 ◽

One Year

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Sirolimus Prolongs Survival after Living Donor Liver Transplantation for Hepatocellular Carcinoma Beyond Milan Criteria: A Prospective, Randomised, Open-Label, Multicentre Phase 2 Trial

Journal of Clinical Medicine ◽

10.3390/jcm9103264 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3264

Author(s):

Kwang-Woong Lee ◽

Seong Hoon Kim ◽

Kyung Chul Yoon ◽

Jeong-Moo Lee ◽

Jae-Hyung Cho ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Living Donor ◽

Milan Criteria ◽

Secondary Outcome ◽

Open Label ◽

Multicentre Phase ◽

Donor Liver Transplantation ◽

Phase 2 Trial ◽

Hcc Recurrence

Sirolimus (SRL) has been reported to benefit patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). This study aimed to compare SRL with tacrolimus (TAC) in living-donor LT (LDLT) recipients beyond the Milan criteria. This study was initially designed to enrol 45 recipients who underwent LDLT for HCC beyond the Milan criteria. At 1 month after LT, the patients were randomly assigned to either SRL or TAC-based treatment, with both groups receiving mycophenolate mofetil. The primary outcome was three-year recurrence-free survival (RFS) and the secondary outcome was overall survival (OS). A total of 42 patients completed the study. HCC recurrence occurred in 8 of 22 (36.4%) patients in the SRL group and in 5 of 22 (25%) patients in the TAC group. No differences in RFS and OS were found between the two groups in simple comparison. The type of immunosuppressant remained a nonsignificant factor for recurrence in multivariate analysis; however, SRL significantly prolonged OS (TAC hazard ratio: 15 [1.3–172.85], p = 0.03) after adjusting for alpha-fetoprotein and positron emission tomography standardised uptake value ratio (tumour/background liver). In conclusion, SRL does not decrease HCC recurrence but prolongs OS after LDLT for HCC beyond the Milan criteria.

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