New models to enhance the assessment of mortality risk in low model for end‐stage liver disease patients: “Objectifying” the subjective

Currently, approximately 3000 patients per year are removed from listing for liver transplantation (LT) in the United States because of the severity of their medical illness or death. In part, this outcome is a result of how health-care providers identify and manage the most suitable candidates before LT. Implemented in 2002, the Model for End-Stage Liver Disease (MELD) score is the current instrument broadly used to riskstratify and prioritize patients for the need for LT. Although reasonably successful in predicting shortterm mortality in all wait-listed patients, it may not adequately capture or identify high-mortality-risk subgroups with lower MELD scores. In this issue of Liver Transplantation, Wedd et al. seek to better characterize these potentially underserved populations, namely, patients with MELD scores 20 who have a higher than expected mortality risk. In particular, the authors examine a host of variables among 41 case subjects matched to 66 case controls with equivalent low MELD scores and other associated features. One key variable is “cirrhotic stage 1-5,” which was defined previously by D’Amico et al. but is conceptually new to the field: (1) cirrhosis without varices or ascites, (2) varices without bleeding, (3) variceal bleeding without ascites, (4) ascites with or without nonbleeding varices, and (5) ascites with variceal bleeding. Wedd et al. conclude that an increasing cirrhotic stage was the key variable associated with liver-related death more than other factors in this low-MELD cohort. This type of cirrhotic staging formally resurrects some level of subjectivity in our modern risk assessment, which traditionally was a concern with the Child-Turcotte-Pugh (CTP) score initially devised in the 1970s for reasons other than LT determination. The CTP score is limited by the following: (1) the explicitly subjective nature of 2 of the 5 parameters (ie, severity of ascites and encephalopathy); (2) the ceiling effect, which placed patients with greatly altered “objective” laboratory values into similar classes; and (3) the focus on a snapshot of disease, such as ascites improvement and subsequent CTP score reduction, which perhaps erroneously implied a reduced mortality risk. Indeed, in 1998, such concerns prompted the hybridization of the CTP score with patient location to create status levels (1, 2A, 2B, and 3) as the main instrument of risk assessment. Although this policy did reduce wait-list mortality, it was eventually plagued by the vagaries and potential wrongdoings of location placement. Ultimately, the transplant community had to develop a more purely objective system of risk assessment. This led directly to the implementation of the MELD score. However, there are persistent concerns with respect to the appropriateness of the objective parameters, the potential for interassay variability and manipulation, and, as mentioned previously, the underserving of lowscore, high-risk patients. Tinkering with the MELD score itself has thus persisted either through exception points [eg, for well-staged hepatocellular carcinoma (accepted)] or through modification of the equation itself (in testing). Examples of the latter include (1) serum sodium (MELD-Na), (2) integrated age and sodium (iMELD), (3) changes in the MELD score over time (DMELD), and (4) the alteration of the coefficients alone