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Pre-transplant alpha-fetoprotein is associated with post-transplant hepatocellular carcinoma recurrence mortality.

ABSTRACT: BACKGROUND:Although liver transplantation may potentially cure hepatocellular carcinoma (HCC), the risk of HCC recurrence is 8%-20% at five years post-transplant. Pre-transplant alpha-fetoprotein (AFP) is a predictor of HCC recurrence, but it is unknown if pre-transplant AFP also predicts survival in patients with recurrence. METHODS:We performed a retrospective cohort study using the United Network for Organ Sharing (UNOS) database between 2002 and 2016. We identified adult transplant recipients with HCC recurrence after liver transplantation for HCC and used Cox regression to compare patient survival among different maximum pre-transplant AFP levels. RESULTS:The cohort (N = 1164) was primarily male, white, and with hepatitis C liver disease. The median time to HCC recurrence was 11.6 months (interquartile range 6.1-26.3). In Cox regression analysis, increasing pre-transplant AFP was associated with poorer survival when adjusting for age, pre-transplant model for end-stage liver disease (MELD), and time to HCC recurrence. For example, patients with pre-transplant AFP ?500ng/mL had a 1.6-fold higher risk of death versus those with AFP ?20ng/mL (P < 0.001). CONCLUSION:Pre-transplant AFP is independently associated with survival in patients with HCC recurrence. These findings further contextualize the importance of pre-transplant AFP in liver transplantation and may improve prognostication for patients with HCC recurrence.

SUBMITTER: Mahmud N

PROVIDER: S-EPMC6635076 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Pre-transplant alpha-fetoprotein is associated with post-transplant hepatocellular carcinoma recurrence mortality.

Mahmud Nadim N John Binu B Taddei Tamar H TH Goldberg David S DS

Clinical transplantation 20190625 7

<h4>Background</h4>Although liver transplantation may potentially cure hepatocellular carcinoma (HCC), the risk of HCC recurrence is 8%-20% at five years post-transplant. Pre-transplant alpha-fetoprotein (AFP) is a predictor of HCC recurrence, but it is unknown if pre-transplant AFP also predicts survival in patients with recurrence.<h4>Methods</h4>We performed a retrospective cohort study using the United Network for Organ Sharing (UNOS) database between 2002 and 2016. We identified adult trans ...[more]

PMID: 31177570

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Project description:BackgroundThis study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after curative resection in the prognosis of patients with hepatocellular carcinoma (HCC) and to develop a novel pre- to postoperative AFP ratio nomogram to predict recurrence free survival (RFS) for HCC patients after curative resection.MethodsA total of 485 pathologically confirmed HCC patients who underwent radical hepatectomy from January 2010 to December 2018 were retrospectively analyzed. The independent prognostic factors of hepatocellular carcinoma were identified by multivariate COX proportional model analysis, and the nomogram model was constructed. The receiver operating characteristic and the C-index were used to evaluate the accuracy and efficacy of the model prediction, the correction curve was used to assess the calibration of the prediction model, and decision curve analysis was used to evaluate the clinical application value of the nomogram model.ResultsA total of 485 HCC patients were divided into the training cohort (n = 340) and the validation cohort (n = 145) by random sampling at a ratio of 7:3. Using X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training cohort was 0.8. In both cohorts, the relapse-free survival of patients with an AFP ratio <0.8 (high-risk group) was significantly shorter than in those with an AFP ratio ≥0.8 (low-risk group) (P < 0.05). An AFP ratio <0.8 was an independent risk factor for recurrence of HCC after curative resection. Based on the AFP ratio, BCLC stage and cirrhosis diagnosis, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 3-, and 5-year RFS was 0.719, 0.690, and 0.708 in the training cohort and 0.721, 0.682, and 0.681 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability.ConclusionThe AFP ratio was a reliable biomarker for tumor recurrence. This easy-to-use AFP ratio-based nomogram precisely predicted tumor recurrence in HCC patients after curative resection.

Project description:INTRODUCTION:serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. METHODS:between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ?15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan-Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. RESULTS:a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. CONCLUSION:N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.

Dataset Information

Pre-transplant alpha-fetoprotein is associated with post-transplant hepatocellular carcinoma recurrence mortality.

Publications

Pre-transplant alpha-fetoprotein is associated with post-transplant hepatocellular carcinoma recurrence mortality.

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