Impact of Preoperative α‐Fetoprotein Level on Disease‐Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Muscari, Fabrice; Guinard, J.-P.; Kamar, Nassim; Péron, Jean‐Marie; Otal, Philippe; Suc, B.

doi:10.1007/s00268-012-1587-z

Cited by 15 publications

(15 citation statements)

References 64 publications

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“…In fact, Yao et al [62] in California require that patients with an initial AFP > 1000 ng/mL have AFP decreased to < 500 ng/mL after loco regional therapy, before undergoing LT. Similarly, in Yamashiki et al [43] 2004 93 United States Prospective 100 ng/mL Drop-out from list Shetty et al [42] 2004 109 United States Retrospective 300 ng/mL Recurrence, death Todo et al [54] 2007 653 Japan Retrospective 200 ng/mL Recurrence 1000 ng/mL Parfitt et al [61] 2007 75 Canada Retrospective 1000 ng/mL Recurrence Pérez-Saborido et al [44] 2007 95 Spain Retrospective 200 ng/mL Recurrence Onaca et al [10] 2007 902 United States Retrospective 200 ng/mL Recurrence Adler et al [86] 2008 226 Belgium Retrospective 100 ng/mL Recurrence Zou et al [45] 2008 303 China Retrospective 1000 ng/mL Fatal recurrence Ioannou et al [50] 2008 5028 United States Retrospective 455 ng/mL Death Xu et al [46] 2009 97 China Retrospective 400 ng/mL Recurrence Toso et al [49] 2009 6478 Canada Retrospective 400 ng/mL Death Lao et al [55] 2009 124 United States Prospective 1000 ng/mL Recurrence Xiao et al [87] 2009 224 China Retrospective 800 ng/mL Death McHugh et al [47] 2010 101 United States Retrospective 100 ng/mL Recurrence, death Levi et al [88] 2010 244 United States Retrospective 100 ng/mL Recurrence Merani et al [66] 2011 6817 United States Retrospective 400 ng/mL Death Lai et al [89] 2011 153 Italy Retrospective 210 ng/mL Recurrence Mailey et al [48] 2011 2253 United States Retrospective 400 ng/mL Death Muscari et al [28] 2012 122 France Retrospective 500 ng/mL Recurrence, death Ciccarelli et al [65] 2012 137 Belgium Retrospective 400 ng/mL Recurrence Wong et al [59] 2013 211 United States Retrospective 400 ng/mL Recurrence Harimoto et al [90] 2013 167 Japan Retrospective 300 ng/mL Recurrence Abdel-Wahab et al [68] 2013 170 Egypt Retrospective 200 ng/mL Recurrence, death Grąt et al [67] 2014 121 Poland Retrospective 100 ng/mL Recurrence Hameed et al [30] 2014 211 United States Retrospective 1000 ng/mL Microvascular invasion Lee et al [91] 2014 69 South Korea Retrospective 200 ng/mL Recurrence Grąt et al [...…”

Section: Evolution Of Afp Over Time: a Critical Markermentioning

confidence: 99%

“…In the following years, multiple studies have confirmed the prognostic role of AFP to predict outcomes after LT. Most of them are based on small cohorts of patients [28,4347] and their main drawbacks are their retrospective designs. Yet all of them display the same tendency: Elevated AFP at the time of LT is associated with a worse prognosis after LT.…”

Section: Afp: a Predictor Of Recurrence After Ltmentioning

confidence: 99%

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Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Charrière¹,

Maulat²,

Suc³

et al. 2016

WJH

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Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.

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Section: Evolution Of Afp Over Time: a Critical Markermentioning

confidence: 99%

Section: Afp: a Predictor Of Recurrence After Ltmentioning

confidence: 99%

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Charrière¹,

Maulat²,

Suc³

et al. 2016

WJH

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“…Higher tumor recurrence Mailey et al [22] Low (≤ 20) Mediun and high: Higher mortality Mediun High (≥ 400) Muscari et al [23] DFS Recurrence Normal 71% 4% 10-150 75% 10% 150-500 57% 24% > 500 46% 62% Chiao et al [24] > 1.000…”

Section: Importancementioning

confidence: 99%

“…In a multivariate analysis, the medium and high AFP groups were associated with higher mortality. Another study [23] correlated the DFS and 5-year recurrence rate to the AFP level. Normal AFP values between 10-150 ng/mL, those from 150-500 ng/mL and those > 500 reduce DFS from 71% to 57%, 46% and 28%, respectively, and increase the recurrence rate from 4% to 10%, 24% and 62%, respectively.…”

Section: Isolated Biological Criteria For the Selection And Prognosismentioning

confidence: 99%

Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future

Soriano¹

2016

WJH

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The aim of liver transplantation (LT) for hepatocellular carcinoma (HCC) is to ensure a rate of disease-free survival similar to that of patients transplanted due to benign disease. Therefore, we are forced to adopt strict criteria when selecting candidates for LT and prioritizing patients on the waiting list (WL), to have clarified indications for bridging therapy for groups at risk for progression or recurrence, and to establish certain limits for downstaging therapies. Although the Milan criteria (MC) remain the standard and most employed criteria for indication of HCC patients for LT by far, in the coming years, criteria will be consolidated that take into account not only data regarding the size/ volume and number of tumors but also their biology. This criteria will mainly include the alpha fetoprotein (AFP) values and, in view of their wide variability, any of the published logarithmic models for the selection of candidates for LT. Bridging therapy is necessary for HCC patients on the WL who meet the MC and have the possibility of experiencing a delay for LT greater than 6 mo or any of the known risk factors for recurrence. It is difficult to define single AFP values that would indicate bridging therapy (200, 300 or 400 ng/mL); therefore, it is preferable to rely on the criteria of a French AFP model score > 2. Other single indications for bridging therapy include a tumor diameter greater than 3 cm, more than one tumor, and having an AFP slope greater than 15 ng/mL per month or > 50 ng/mL for three months during strict monitoring while on the WL. When considering the inclusion of patients on the WL who do not meet the MC, it is mandatory to determine their eligibility for downstaging therapy prior to inclusion. The upper limit for this therapy could be one lesion up to 8 cm, 2-3 lesions with a total tumor diameter up to 8 cm, or a total tumor volume of 115 cm 3 . Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future the WL should take into account the recently described HCC model for end-stage liver disease, which considers hepatic function, HCC size and the number and the log of AFP values. This formula has been calibrated with the survival data of non-HCC patients and produces a dynamic and more accurate assessment model.

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“…Extended criteria [9,10,11] have aimed to improve the selection of appropriate LT recipients among patients with advanced HCC; however, most of these classifications are also primarily based on morphological characteristics rather than on assessments of tumor aggressiveness and have failed to be generally accepted. Tumor biology has been shown to correlate with clinicopathological variables including tumor differentiation, the presence of microvascular tumor invasion, and α-fetoprotein (AFP) levels [12,13,14,15]. However, only AFP can be easily obtained before LT and thus support patient selection, whereas microvascular invasion and tumor grading cannot be reliably assessed prior to the recipient hepatectomy [16].…”

Section: Introductionmentioning

confidence: 99%

Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Ανδρέου¹,

Bahra²,

Guel³

et al. 2015

Eur Surg Res

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Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates. Methods: Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed. Results: Multivariate analysis in the entire cohort identified DNA index >1.5 (p < 0.0001), α-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p < 0.0001) was the only predictor of worse overall survival in multivariate analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of worse overall survival. Consequently, patients beyond the Milan criteria with a combined favorable DNA index ≤1.5 and AFP ≤200 ng/ml had a median survival (147 months) comparable to that of patients within the Milan criteria. Conclusions: DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.

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Impact of Preoperative α‐Fetoprotein Level on Disease‐Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Abstract: This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.

Cited by 15 publications

References 64 publications

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future

Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

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