Better outcomes in managing hepatocellular carcinoma

Sub-optimal selection of liver cancer patients for liver transplantation

Liver transplantation offers a curative-intent treatment for patients with HCC in early stages of the disease. This is a complex and costly procedure that is limited by the low availability of organs for transplantation, being offered only to patients likely to benefit from the procedure in the long term. Current pre-transplant selection criteria are known to:

1) include patients who eventually relapse, resulting in the organ wastage (approximately 16%), and

2) exclude patients who ultimately would have good outcomes, thereby denying them a potentially curative treatment.

Moreover, these criteria rely on imaging-based assessments, such as computed tomography (CT) and magnetic resonance imaging (MRI), which tend to underestimate the actual tumor size and/or burden in approximately 13-33% of cases.

These disparities between preoperative imaging and postoperative pathology are associated with poorer outcomes, including higher post-transplant recurrence rates and reduced survival. 

HepatoPredict is a new in vitro diagnostics (IVD) test that provides accurate prognostic information for HCC patients.

HepatoPredict outperforms clinical criteria for liver transplant patient selection

Recurrence-free survival demonstrates the discriminative power of HepatoPredict

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HepatoPredict selects patients for liver transplantation more accurately

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Sub-optimal management of liver cancer patients after liver transplantation

Despite the use of strict selection criteria for liver transplantation, recurrence of HCC occurs in as much as 8-20% of patients, most commonly in the first 2 years after surgery.

Despite the proven value and cost-effectiveness of patient surveillance, the lack of standardized guidance and appropriate risk stratification practices leads to practice heterogeneity and poorer clinical outcomes.

HepatoPredict is intended to accurately and rapidly identify patients at high-risk of post-LT recurrence, thereby improving the management of transplanted patients.

HepatoPredict shows good performance in predicting HCC recurrence after liver transplant

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Other applications

Collaborations

We are expanding HepatoPredict clinical validation in a series of collaborative studies.

More scientific evidence

Scientific Publications

Pinto-Marques H, Cardoso J, Silva S, Neto JL, Gonçalves-Reis M, Proença D, Mesquita M, Manso A, Carapeta S, Sobral M, Figueiredo A, Rodrigues C, Milheiro A, Carvalho A, Perdigoto R, Barroso E, Pereira Leal JB (2022) A gene expression signature to select hepatocellular carcinoma patients for liver transplantation. Annals of Surgery.

https://pubmed.ncbi.nlm.nih.gov/35916378/

Gonçalves-Reis M, Proença D, Frazão L, Neto JL, Silva S, Pinto-Marques H, Pereira Leal JB, Cardoso J. (2024) Analytical validation and algorithm improvement of HepatoPredict kit to assess hepatocellular carcinoma prognosis before a liver transplantation. Practical Laboratory Medicine.

https://pubmed.ncbi.nlm.nih.gov/38371895/

Andrade R, Perez J, Silva S, Miskinyte M, Quaresma MC, Frazão L, Peixoto C, Cubells A, Montalva E, Figueiredo A, Cipriano MA, Gonçalves-Reis M, Proença D, Folgado A, Pereira-Leal JB, Oliveira RC, Pinto-Marques H, Tralhão JG, Berenguer M, Cardoso J. (2025) HepatoPredict accurately selects hepatocellular carcinoma patients for liver transplant regardless of tumor heterogeneity. Cancers.

https://pubmed.ncbi.nlm.nih.gov/39941867/

Frazão L.P., Quaresma M.C., Pereira-Leal J., Duvoux C., Cardoso J. Hepatocellular carcinoma transplant criteria show poor negative predictive value: a systematic review and meta-analysis (2025). Journal of Personalized Medicine.

https://doi.org/10.3390/jpm15100449

Conferences

EASL 2025

Andrade R, Silva S, Miskinyte M, Quaresma M, Frazão L, Peixoto C, Figueiredo A, Cipriano M, Gonçalves-Reis M, Proença D, Folgado A, Pereira-Leal J, Oliveira R, Pinto-Marques H, Tralhão J, Cardoso J. HepatoPredict has a good prognostic value in patients with hepatocellular carcinoma independently of biopsied nodule. EASL Annual Congress, Amsterdam, The Netherlands (May 7-10, 2025). [Poster]

EASL 2024

Silva GS, Pérez J, Frazão L, Peixoto C, Cubells A, Montalvá E, Figueiredo A, Proença D, Pereira-Leal J, Pinto-Marques H, Berenguer M, Cardoso J. Prognosticating Hepatocellular carcinoma before and after liver transplantation with HepatoPredict. EASL Annual Congress, Millan, Italy (June 5-8, 2024). [Poster + Oral presentation]

ILTS 2024

Frazão LP, Pereira-Leal JB, Duvoux C, Cardoso J. The best criteria for the selection of hepatocellular carcinoma patients for liver transplantation: a systematic review and meta-analysis. ILTS Annual Congress, Houston, USA (May 1−4, 2024). [ePoster]

ILTS 2023

Cardoso J, Proença D, Oliveira RC, Frazão LP, Andrade R, Gonçalves-Reis M, Neto JL, Pereira-Leal JB, Tralhão JG. Testing HepatoPredict kit performance in liver transplantation prognosis for hepatocellular carcinoma when facing intra- and inter-tumoral heterogeneity [ePoster]. ILTS Annual Congress, Rotterdam, Netherlands (May 3-6, 2023).

ILTS 2022

Cardoso J, Marques HP, Mesquita M, Manso A, Carapeta S, Sobral M, Silva S, Rodrigues C, Carvalho A, Milheiro A, Perdigoto R, Barroso B, Pereira-Leal J (2022). New criteria in liver transplantation for hepatocellular carcinoma: a combined molecular and clinical predictor of survival. [Oral presentation]. Transplantation. https://ilts.org/education/abstracts

EASL 2021

Cardoso J, Marques HP, Mesquita M, Manso A, Carapeta S, Sobral M, Silva S, Rodrigues C, Carvalho A, Milheiro A, Perdigoto R, Barroso B, Pereira-Leal J (2021). A new tool for predicting survival in liver transplantation for hepatocellular carcinoma combining molecular and clinical variables [Poster Presentation]. Journal of Hepatology, 75(2), S475.  https://doi.org/10.1016/S0168-8278(21)01843-2 

Clinical Trials

Clinical Trials

HepatoPredict is being validated in an interventional clinical study at Centro Hospital de Lisboa Central (NCT04499833). In this trial, patients with HCC in cirrhotic liver and outside “Milan criteria” are suggested to be submitted to HepatoPredict test. If the test predicts a good prognosis after liver transplantation, the patient will be proposed for the procedure using marginal livers or livers from patients with Familial Amyloid Polyneuropathy, and followed up for 5 years after transplantation.

References

  • Mehta et al (2022) A novel waitlist dropout score for hepatocelular carcinoma – identifying a threshold that predicts worse post-transplant survival. Journal of Hepatology. doi: 10.1016/j.jhep.2020.10.033
  • Sokolich et al (2020) HCC Liver Transplantation Wait List Dropout Rates Before and After the Mandated 6-Month Wait Time. The American Surgeon. doi: 10.1177/0003134820942165
  • Hoof et al (2022) External Validation of the RETREAT Score for Prediction of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers. doi: 10.3390/cancers14030630
  • Stras et al (2022) Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models. Annals of Transplantation. doi: 10.12659/AOT.934924
  • Pelizzaro et al (2021) Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers. doi: https://doi.org/10.3390/cancers13194882 
  • Herreras et al (2019) Milan-out Criteria and Worse Intention-to-Treat Outcome Post-liver Transplantation. Transplantation. doi: 10.1097/TXD.0000000000000934 
  • Brandão et al (2024) Performance of eight predictive models for hepatocellular carcinoma recurrence after liver transplantation: A comparative study. Ann Hepatol. doi: 10.1016/j.aohep.2023.101184. 
  • Lee et al (2020) Surveillance for HCC After Liver Transplantation: Increased Monitoring May Yield Aggressive Treatment Options and Improved Postrecurrence Survival. Transplantation. doi: 10.1097/TP.0000000000003117.
  • Straś et al (2022) Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models. Ann Transplant. doi: 10.12659/AOT.934924.
  • Degroote et al (2022) Different Models to Predict the Risk of Recurrent Hepatocellular Carcinoma in the Setting of Liver Transplantation. Cancers. doi.org/10.3390/cancers14122973
  • Frazão et al (2025) Hepatocellular Carcinoma Transplant Criteria Show Poor Negative Predictive Value: A Systematic Review and Meta-Analysis. Journal of Personalized Medicine. doi.org/10.3390/jpm15100449
  • Akabane et al (2025) Impact of disparity between imaging and pathological tumor size on cancer-specific prognosis among patients with hepatocellular carcinoma
     Eur J Surg Oncol. doi: 10.1016/j.ejso.2025.109683
  • Mohamed et al (2023) Radiological-histopathological discordance in patients transplanted for HCC and its impact on post-transplant outcomes. Cancer Med. doi: 10.1002/cam4.6161.
  • Ecker et al (2018) Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation. Transplantation. doi: 10.1097/TP.0000000000002056.
  • Aggarwal et al (2020) A National Survey of Hepatocellular Carcinoma Surveillance Practices Following Liver Transplantation. Transplant Direct. doi: 10.1097/TXD.0000000000001086.