Abstract

Background: Adolescents constitute a unique waitlist cohort that is distinct from younger children and adults. MELD 3.0, which was developed and validated in an adult population of liver transplant candidates with chronic liver disease, improves upon MELD-Na, incorporating sex and albumin as additional variables, updating coefficients, and adding relevant interactions. MELD 3.0 is proposed to replace MELD-Na in the current liver allocation system for both adult and adolescents aged 12-17. We evaluated the predictive performance of MELD-Na and MELD 3.0 for 90-day waitlist mortality risk among adolescent liver transplant registrants.

Methods: New waitlist registrations for liver transplant among individuals aged 12-17 and aged 18-25 for comparison were identified using OPTN data from Nov 17 2004 to Dec 31 2021. MELD 3.0 was calculated by: 1.33 (if female) + 4.56*log_e(bilirubin) + 0.82*(137-Na) – 0.24*(137-Na)*log_e(bilirubin) + 9.09*log_e(INR) + 11.14*log_e(creatinine) + 1.85*(3.5-albumin) – 1.83*(3.5-albumin)*log_e(creatinine) + 6. Adolescents aged 12-17 were granted the 1.33 points regardless of sex, as proposed by the OPTN, as differences in muscle mass and thus creatinine between sexes are not established in this age group. The predictive performance was assessed using a time-dependent concordance (c) statistic, with a c-statistic closer to 1 signifying a model with better discrimination between individuals that did or did not experience the outcome (death). Survival was estimated using Kaplan-Meier methods and Cox regression, with censoring at the time of liver transplant.

Results: There were 1,315 eligible listings for candidates aged 12-17, and 1,856 aged 18-25. Registrants aged 12-17 were more likely to be female (52.5% v 48.8%, p=0.04) and to have a diagnosis of biliary atresia or genetic disease (p<0.01), compared to registrants aged 18-25. Registrants aged 18-25 were more likely to have a diagnosis of viral hepatitis or other cholestatic disease, ascites, or encephalopathy (p<0.01). The median MELD-Na at listing was lower among registrants 12-17 (14 v 18, p<0.01), as was median MELD 3.0 (16 v 19, p<0.01), compared to registrants 18-25. Overall, 90-day survival in the adolescent group was 97.1%, compared to 95.3% for those aged 18-25 (log-rank p 0.014). In the Cox regression analysis, MELD 3.0 was associated with an increased hazard of mortality (HR 1.23, 95% CI 1.17-1.28) in adolescents. Among registrants aged 12-17, the c-statistic for 90-day waitlist survival using MELD 3.0 was 0.911, compared with 0.891 using MELD-Na (p=0.10).

Conclusion: The predictive performance of MELD 3.0 in adolescent liver transplant registrants was robust with a c-statistic of 0.911 for 90-day waitlist mortality. While MELD 3.0 was initially validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplant.