Comparison of Models for Tumor Recurrence after Liver Transplantation for the Patients with Hepatocellular Carcinoma: A Multicenter Long-Term Follow-Up Study

Young Chang, Yuri Cho, Jeong-Hoon Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Dong Hyun Sinn, Bo Hyun Kim, Seoung Hoon Kim, Nam-Joon Yi, Kwang-Woong Lee, Jong Man Kim, Joong-Won Park, Yoon Jun Kim, Jung-Hwan Yoon, Jae-Won Joh, Kyung-Suk Suh, Young Chang, Yuri Cho, Jeong-Hoon Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Dong Hyun Sinn, Bo Hyun Kim, Seoung Hoon Kim, Nam-Joon Yi, Kwang-Woong Lee, Jong Man Kim, Joong-Won Park, Yoon Jun Kim, Jung-Hwan Yoon, Jae-Won Joh, Kyung-Suk Suh

Abstract

Background and aims: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries.

Methods: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model.

Results: The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts.

Conclusions: The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT.

Keywords: MoRAL score; hepatocellular carcinoma; living donor liver transplantation; survival; validation.

Conflict of interest statement

These authors disclose the following: Lee, J.H. reports receiving lecture fee from GreenCross Cell, Daewoong Pharmaceuticals, and Gilead Korea; Yu, S.J. reports lecture fee from Bayer HealthCare Pharmaceuticals; Kim, Y.J. research grants from Bristol-Myers Squibb, Roche, J.W. Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, Samjin Pharmaceuticals, and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals, and Handok Pharmaceuticals; Yoon, J.H., research grants from Bayer HealthCare Pharmaceuticals, Daewoong Pharmaceuticals, and Bukwang Pharmaceuticals. No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1
Kaplan-Meier estimates of cumulative risk of HCC recurrence (A) and overall survival (B) according to the MoRAL score. The low-MoRAL group (shown as a continuous line) was associated with significantly lower risk of HCC recurrence and overall death than the high-MoRAL group (shown as a dashed line).
Figure 1
Figure 1
Kaplan-Meier estimates of cumulative risk of HCC recurrence (A) and overall survival (B) according to the MoRAL score. The low-MoRAL group (shown as a continuous line) was associated with significantly lower risk of HCC recurrence and overall death than the high-MoRAL group (shown as a dashed line).
Figure 2
Figure 2
The ROC curves for 1-year (A), 3-year (B) and 5-year (C) HCC recurrence of the MoRAL score (shown as a continuous line) and the other models (shown as various dashed lines). The AUROCs of the MoRAL score for 1-year, 3-year, and 5-year recurrence risk were significantly higher than those of the other models.
Figure 2
Figure 2
The ROC curves for 1-year (A), 3-year (B) and 5-year (C) HCC recurrence of the MoRAL score (shown as a continuous line) and the other models (shown as various dashed lines). The AUROCs of the MoRAL score for 1-year, 3-year, and 5-year recurrence risk were significantly higher than those of the other models.

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