Dataset Information

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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Publications

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:ImportanceAccurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured.ObjectiveTo externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models.Design, setting, and participantsA retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020.Main outcomes and measuresThe primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome.ResultsOf 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0.Conclusions and relevanceThis study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.

Project description: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. 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. 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. 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.

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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