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. Many criteria have been proposed over the years to identify these patients, but these are still sub-optimal.

On the other hand, some patient selection criteria are quite restrictive, excluding patients that could benefit from liver transplantation. While inclusive criteria are associated with increased costs and risks related to a second surgical intervention due to cancer recurrence, exclusive criteria imply the denial of a curative treatment to a patient that would benefit from it. 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.

Recently, predictive models for HCC recurrence after liver transplantation have been proposed. However, it is clear that there is still a need for more robust and reliable predictive models that can assist in personalized patient management and improve long-term outcomes in the field of HCC liver transplantation.

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. HepatoPredict accurately selects hepatocellular carcinoma patients for liver transplant regardless of tumor heterogeneity. (Submitted)

Frazao LP, Pereira-Leal JB, Duvoux C, Cardoso J. Role of accuracy measures in selecting hepatocellular carcinoma patients for liver transplantation A systematic review and meta-analysis. medRxiv. 2024;:2024.12.16.24319098.

https://www.medrxiv.org/content/10.1101/2024.12.16.24319098v1

Conference Presentations

Conference Presentations

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 (2023). 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 ABM, Rodriguez S, Marroni CA, Junior AMF, Fernandes MV, Mucenic M. Performance of eight predictive models for hepatocellular carcinoma recurrence after liver transplantation: A comparative study. Ann Hepatol. 2024 Mar-Apr;29(2):101184. doi: 10.1016/j.aohep.2023.101184. Epub 2023 Nov 24.
  • Lee DD, Sapisochin G, Mehta N, Gorgen A, Musto KR, Hajda H, Yao FY, Hodge DO, Carter RE, Harnois DM. Surveillance for HCC After Liver Transplantation: Increased Monitoring May Yield Aggressive Treatment Options and Improved Postrecurrence Survival. Transplantation. 2020 Oct;104(10):2105-2112. doi: 10.1097/TP.0000000000003117.
  • Straś WA, Wasiak D, Łągiewska B, Tronina O, Hreńczuk M, Gotlib J, Lisik W, Małkowski P. Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models. Ann Transplant. 2022 Jan 26;27:e934924. doi: 10.12659/AOT.934924.