Variation in intention-to-treat survival by MELD subtypes: All models created for end-stage liver disease are not equal.

Background & aims: Kidney dysfunction is a major determinant of prognosis in patients with decompensated cirrhosis awaiting transplantation. We hypothesized that for identical model for end-stage liver disease (MELD) scores at listing, outcomes before and after liver transplantation may vary if the predominant driver of the MELD score is serum creatinine (Cr) vs. serum bilirubin (Br) or international normalized ratio (INR).

Methods: We evaluated all adult patients registered for liver transplantation (LT) between 2016-2020 and excluded patients receiving MELD exceptions or undergoing dual organ transplantation. Using K-Means clustering analysis, we classified each patient as MELD-Br, MELD-INR or MELD-Cr depending on the dominant variable for their MELD score. The primary outcome was intent-to-treat (ITT) survival, defined as survival within 1 year from listing with or without LT.

Results: MELD scores of LT waitlist registrants were clustered into three subtypes: MELD-Br (n = 13,658), MELD-INR (n = 13,809), and MELD-Cr (n = 12,412). One-year ITT survival rates were 78% (MELD-Br), 75% (MELD-INR), and 65% (MELD-Cr), p <0.01. ITT survival was lower for each MELD subtype for females compared to males (e.g. MELD-Cr: 63% females vs. 67% males, p <0.0001). The MELD-Cr subtype had the highest MELD at listing (MELD-Cr 23.4 vs. MELD-Br 19.2 vs. MELD-INR 21.0) and the largest decline in MELD over 3 months (23% vs. 12% vs. 21%). In adjusted analyses including MELD-Na, MELD-Cr was associated with higher waitlist mortality (hazard ratio 1.339, 95% CI 1.279-1.402) and lower LT rates (hazard ratio 0.688, 95% CI 0.664-0.713) compaed to the other subtypes.

Conclusions: For equivalent listing practices, registrants with the MELD-Cr subtype have lower ITT survival. MELD subtype may serve as a more sophisticated variable for dynamic assessment of mortality risk and to guide organ allocation.

Impact and implications: The model for end-stage liver disease (MELD) score is an excellent predictor of waitlist mortality; however, our work highlights that the driver of a patient's MELD score matters and particularly those driven by elevated creatinine are associated with lower 1-year intent-to-treat survival. The 1-year intent-to-treat survival is also lower for women compared to men within the Cr-dominant subtype. These results are important for physicians and patients undergoing LT evaluation as creatinine may serve as a marker of prognosis and even if creatinine levels improve the prognosis remains poor, necessitating discussion about alternative pathways for transplant. Our work also highlights that the type of kidney injury matters, in that those with acute kidney injury were more likely to die or remain on the waitlist than those with chronic kidney disease within the creatinine-dominant subtype.