MoRAaL Score: Clinical Application in Hepatocellular Carcinoma and Liver Transplantation
The MoRAaL (Model of Recurrence After Liver transplant) score is a validated prognostic tool used to predict tumor recurrence risk in patients with hepatocellular carcinoma (HCC) undergoing liver transplantation, particularly for those beyond the Milan criteria, using preoperative biomarkers to guide patient selection and post-transplant surveillance strategies. 1, 2
Primary Clinical Applications
Patient Selection for Liver Transplantation
The MoRAaL score identifies HCC patients beyond Milan criteria who may still benefit from liver transplantation, with patients scoring ≤314.8 achieving 5-year recurrence-free survival of 66.3% and overall survival of 82.6%, comparable to within-Milan criteria patients 1
The score uses two readily available serum biomarkers: protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP), providing objective measures of tumor biology that the Milan criteria lack 1, 2
Patients with MoRAaL scores >314.8 have significantly worse outcomes, with a 5.29-fold higher risk of recurrence and 2.59-fold higher risk of death compared to low-score patients 1
Risk Stratification Models
The MoRAaL system exists in three validated versions, each serving distinct clinical timepoints:
Pre-MORAL Score (Preoperative Assessment)
- Incorporates three preoperatively available factors: neutrophil-lymphocyte ratio (NLR) ≥5, AFP >200 ng/mL, and tumor size >3 cm 2
- Assigns points based on hazard ratios: NLR ≥5 (6 points), AFP >200 (4 points), size >3 cm (3 points), with total scores ranging 0-13 points 2
- Demonstrates superior predictive accuracy with c-statistic of 0.82 compared to Milan criteria's 0.63 for predicting recurrence 2
- High-risk patients (maximum score) have 5-year recurrence-free survival of only 17.9% versus 98.6% for low-risk patients 2
Post-MORAL Score (Postoperative Assessment)
- Uses four postoperative pathologic factors: grade 4 HCC (5.6-fold increased risk), vascular invasion (2.0-fold risk), size >3 cm (3.2-fold risk), and number >3 tumors (1.8-fold risk) 2
- Achieves c-statistic of 0.87, outperforming both Milan criteria and the pre-MORAL score for recurrence prediction 2
Combo-MORAL Score (Combined Assessment)
- Integrates both pre- and post-operative factors to achieve the highest predictive accuracy with c-statistic of 0.91 2
- Provides the most comprehensive risk stratification for long-term surveillance planning 2
Clinical Decision Algorithm
Step 1: Initial Evaluation
- Calculate pre-MORAL score using NLR, AFP, and imaging-determined tumor size before listing for transplantation 2
- For patients beyond Milan criteria with pre-MORAL ≤314.8 and no extrahepatic metastasis, proceed with transplant evaluation 1
- For patients with pre-MORAL >314.8, consider alternative treatments or downstaging protocols before transplantation 2
Step 2: Post-Transplant Assessment
- Calculate post-MORAL score using explant pathology (tumor grade, vascular invasion, size, number) 2
- Patients with high post-MORAL scores require intensified surveillance protocols given elevated recurrence risk 2
Step 3: Surveillance Stratification
- Low combo-MORAL patients: standard surveillance intervals may be appropriate 2
- High combo-MORAL patients: consider shortened surveillance intervals and earlier intervention for suspected recurrence 2
Important Clinical Caveats
Comparison with Milan Criteria
- Within-Milan patients with high MoRAaL scores demonstrate 2.56-fold higher recurrence risk compared to beyond-Milan patients with low MoRAaL scores, highlighting that tumor biology matters more than size/number alone 1
- The MoRAaL score provides objective biological assessment that Milan criteria lack, as Milan relies solely on anatomic tumor burden 1, 2
Validation and Reliability
- The score maintains consistent discriminant function across internal validation (c-index 0.87) and external validation (c-index 0.84) cohorts 1
- The MoRAaL score correlates significantly with explant histology, confirming its biological validity 1
Limitations to Consider
- The score was developed and validated in living donor liver transplantation cohorts, primarily from Korean centers, so applicability to deceased donor transplantation requires consideration 1
- The 314.8 cutoff represents the 75th percentile value in the derivation cohort and may require institutional validation 1
- Patients must have no extrahepatic metastasis for the score to be applicable, as this represents an absolute contraindication regardless of score 1
Distinction from Other Scoring Systems
The MoRAaL score should not be confused with moral injury assessment tools (MISS-HP) used in healthcare worker wellbeing research, which measure psychological distress from ethical conflicts 3, 4, 5
The MoRAaL score is also distinct from the SOFA score (Sequential Organ Failure Assessment), which evaluates multi-organ dysfunction in critically ill septic patients rather than cancer recurrence risk 6, 7, 8