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

Giard, Jeanne-Marie; Mehta, Neil; Dodge, Jennifer L.; Roberts, John P.; Yao, Francis Y.

doi:10.1097/tp.0000000000002094

Cited by 38 publications

(37 citation statements)

References 22 publications

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“…This AFP 'slope' has been thought to be more reflective of the dynamic nature of tumor biology than just a single value. Giard et al 26 recently looked at 336 patients undergoing OLT for HCC who were within Milan criteria. Nearly all (98%) of the patients had LRT at some time prior to transplant and the AFP slope was estimated by the AFP values during this pretransplant period.…”

Section: Biomarkersmentioning

confidence: 99%

Liver Transplantation Beyond Milan Criteria

Lingiah

Niazi

Olivo

et al. 2020

Journal of Clinical and Translational Hepatology

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, being the fifth most common cancer and the third most common cause of cancer-related mortality. The incidence of HCC has been rising in the USA over the last 20 years. Liver transplantation is an optimal treatment option, as it eliminates HCC as well as the underlying liver disease. The Milan criteria (1 lesion greater than or equal to 2 cm and less than or equal to 5 cm, or up to 3 lesions, each greater than or equal to 1 cm and less than or equal to 3 cm) have been adopted by many transplant societies worldwide as the criteria to determine whether patients with HCC can move forward with liver transplantation. However, many believe that the Milan criteria may be too strict in regard to its size requirements for lesions. This has led to a number of expanded criteria for liver transplantation, concerning both overall size and number of lesions, as well as incorporation of other markers of tumor biology. Tumor markers, such as alphafetoprotein, can also be used to follow treatment of HCC and possibly exclude patients from transplant. HCC presenting beyond Milan criteria can also be down-staged with locoregional therapy. Monitoring response to locoregional therapy and longer wait times after locoregional therapy prior to transplant can serve as surrogate markers of tumor biology as well.

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Section: Biomarkersmentioning

confidence: 99%

Liver Transplantation Beyond Milan Criteria

Lingiah

Niazi

Olivo

et al. 2020

Journal of Clinical and Translational Hepatology

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“…Similarly, Halazun et al showed that AFP responders to LRT (e.g., AFP 200‐1000 ng/mL that decreased to <200 ng/mL with LRT) had significantly better post‐LT outcome than AFP nonresponders. Rising AFP slope of more than 7.5 to 15 ng/mL/month despite LRT also predicts poor post‐LT outcome . Additional serum marker cutoffs associated with inferior post‐LT outcome include AFP‐L3 greater than 35%, des‐γ carboxyprothrombin (DCP) greater than 400 mAU/mL (or 7.5 ng/mL), and neutrophil‐to‐lymphocyte ratio (NLR) greater than 5 (Table ), although these findings require confirmation.…”

Section: Serum Markersmentioning

confidence: 99%

What Are the Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma?

Mehta

Yao

2019

Clinical Liver Disease

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“…Patients with higher baseline IGF-1, had 33% lower chance of liver recurrence and 29% lower rate of death following transplantation. The recurrence of HCC after liver transplant was associated with a poor prognosis, and identification of high-risk groups may allow tailoring of immunosuppression regimens, selection of patients for closer surveillance, or appropriate enrolment in trials of adjuvant therapy, such as sorafenib (45)(46)(47)(48)(49). To the best of our knowledge, we provide the first description of preoperative IGF-1 levels correlation with outcomes following liver transplant in an HCC population.…”

Section: Discussion Discussionmentioning

confidence: 92%

An Observational Study of Circulating Plasma and Serum Insulin-Like Growth Factor 1 as Prognostic Biomarkers in Surgical Hepatocellular Carcinoma Patients

Kaseb¹,

Dima²,

Pestana³

et al. 2019

SGO

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Identification of biomarkers that correlate with prognosis is crucial in hepatocellular carcinoma (HCC) because of the high recurrence rates seen after surgical treatments. Serum levels of α-fetoprotein (AFP) are widely used clinically, but the prognostic value of AFP remains unclear. AFP levels are influenced not only by the presence of HCC but also by the severity of the underlying liver disease. Furthermore, AFP could be normal in up to 30% of HCC patients. Thus, additional biomarkers are needed. Insulin-like growth factors 1 (IGF-1) is a growth factor with dose-dependent proliferation and anabolic effects, and its interaction with IGF-1 receptor (IGF-1R) may promote tumor progression. On the other hand, hepatic synthesis of IGF-1 is significantly reduced due to underlying chronic liver disease in HCC patients, and previous studies demonstrated that circulating IGF-1 is a useful predictor of hepatic reserve in HCC patients. We evaluated circulating IGF-1 and AFP levels in a cohort of HCC patients undergoing liver resection or liver transplantation at a single institution (Fundeni Clinical Institute, Romania). We found that plasma IGF-1 was decreased in HCC patients as compared with healthy individuals, and that plasma IGF-1 was associated with the presence of cirrhosis in HCC patients. In addition, we found that plasma IGF-1 levels were significantly associated with disease-free survival (DFS) and overall survival (OS). This correlation was due to the significant association between higher IGF-1 and more favorable DFS and OS following liver transplantation. Independent validation of this biomarker is warranted in the setting of liver transplantation to confirm and further define the prognostic implications of plasma IGF-1 in HCC patients.

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

Abstract: AFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT.

Cited by 38 publications

References 22 publications

Liver Transplantation Beyond Milan Criteria

Liver Transplantation Beyond Milan Criteria

What Are the Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma?

An Observational Study of Circulating Plasma and Serum Insulin-Like Growth Factor 1 as Prognostic Biomarkers in Surgical Hepatocellular Carcinoma Patients

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