Delta‐slope of alpha‐fetoprotein improves the ability to select liver transplant patients with hepatocellular cancer

Lai, Quirino; Inostroza, Milton; Juri, Juan Manuel Rico; Goffette, Pierre; Lerut, Jan

doi:10.1111/hpb.12486

Cited by 21 publications

(11 citation statements)

References 25 publications

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“…Although MC was critical to widespread success in LT for HCC, its utility has decreased over time attributed to changes in clinical practice. Many models were developed to replace MC and several did possess improved prognostic discrimination (6)(7)(8)16,20,(27)(28)(29) ; however, most fell by the wayside because of poor generalizability. Those models were developed in single institutes where the patient population and treatment strategy are homogeneous.…”

Section: Discussionmentioning

confidence: 99%

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

et al. 2019

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Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre‐LT levels of alpha‐fetoprotein, Model for End‐Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest‐risk patients (HALTHCC 0‐5) had lower rates of VI and PDC than the highest‐risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2‐14.2] vs. 70.6% [48.3‐92.9] and PDC:4.6% [0.1%‐9.8%] vs. 47.1% [22.6‐71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C‐index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C‐index = 0.71) and OS (C‐index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre‐LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.

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Section: Discussionmentioning

confidence: 99%

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

et al. 2019

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“…Lastly, in a study by Lai et al from Brussels, 124 patients transplanted for HCC were evaluated and a “delta-slope,” calculated with 3 AFP data points, was used to predict outcomes after LT listing. AFP slope >15 ng/mL per month was a significant predictor of intention-to-treat death and HCC recurrence after LT. 16…”

Section: Discussionmentioning

confidence: 99%

“…These studies also did not adequately account for fluctuations of AFP commonly seen in chronic liver disease. 12–16 Moreover, the slope threshold at which the recurrence can be predicted varied from 1 study to another. The primary aim of this study was to examine the association between AFP slope and post-LT HCC recurrence in patients awaiting LT, with AFP slope more precisely estimated from multiple data points over time.…”

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confidence: 99%

Alpha-Fetoprotein Slope >7.5 ng/mL per Month Predicts Microvascular Invasion and Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma

et al. 2018

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“…The most used ones are alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) (55). The initial serum levels and its variation during locoregional treatment are independent predictors of prognosis (56,57). They can be combined with traditional variables of tumors recurrence to select patients with more advanced HCC but favorable biological behavior, resulting in comparable outcomes to patients within MC.…”

Section: Discussionmentioning

confidence: 99%

Living donor liver transplantation for hepatocellular cancer: an (almost) exclusive Eastern procedure?

Pinheiro

Waisberg

Nacif

et al. 2017

Transl. Gastroenterol. Hepatol.

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Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and it is linked with chronic liver disease. Liver transplantation (LT) is the best curative treatment modality, since it can cure simultaneously the underlying liver disease and HCC. Milan criteria (MC) are the benchmark for selecting patients with HCC for LT, achieving up to 91% 1-year survival post transplantation. However, when considering intention-to-treat (ITT) rates are substantially lower, mainly due dropout. Additionally, Milan criteria (MC) are too restrictive and more inclusive criteria have been reported with good outcomes. Mainly, in Eastern countries, deceased donors are scarce, therefore Asian centers have developed living-donor liver transplantation (LDLT) to a state-of-art status. There are many eastern centers reporting huge numbers of LDLT with outstanding results. Regarding HCC patients, they have reported many criteria including more advanced tumors achieving reasonable outcomes. Western countries have well-established deceased-donor liver transplantation (DDLT) programs. However, organ shortage and restrictive criteria for listing patients with HCC endorses LDLT as a good option to offer curative treatment to more HCC patients. However, there are some controversial reports claiming higher rates of HCC recurrence after LDLT than DDLT. An extensive review included 30 studies with cohorts of HCC patients who underwent LDLT in both East and West countries. We reported also the results of our Institution, in Brazil, where it was performed the first LDLT. This review also addresses the eligibility criteria for transplanting patients with HCC developed in Western and Eastern countries.

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Delta‐slope of alpha‐fetoprotein improves the ability to select liver transplant patients with hepatocellular cancer

Abstract: Integration of the AFP delta-slope with conventional criteria may further improve patient selection and post-LT outcomes; prospective studies are needed to validate the present proposed model.

Cited by 21 publications

References 25 publications

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

Alpha-Fetoprotein Slope >7.5 ng/mL per Month Predicts Microvascular Invasion and Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma

Living donor liver transplantation for hepatocellular cancer: an (almost) exclusive Eastern procedure?

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