Moderate ascites identifies patients with low model for end-stage liver disease scores awaiting liver transplantation who have a high mortality risk

Abstract

Donor livers are offered to patients with the highest risk of death. How ascites could inform risk models to reduce liver transplant wait-list mortality is unclear. All adult candidates for primary liver transplantation for cirrhosis without exception points who were registered with the Organ Procurement and Transplantation Network from 2005 to 2007 composed our study cohort. Using Cox models and advanced discriminative metrics and paying attention to geographic disparities, we evaluated the additional risk discrimination of moderate ascites over that of the Model for End-Stage Liver Disease (MELD) or the Model for End-Stage Liver Disease plus serum sodium (MELD-Na) alone for the prediction of 90-day wait-list mortality. Additional analyses examined lower mortality risk candidates and those listed in high-demand, low-supply United Network for Organ Sharing regions in which accounting for ascites may most significantly affect wait-list mortality. Between 2005 and 2007, 18,124 subjects were listed for liver transplantation. Mortality was higher in patients with moderate ascites (15.4% versus 6.0%, P < 0.0001), and this risk persisted despite adjustments for MELD (hazard ratio = 1.58, 95% confidence interval = 1.42-1.76) and MELD-Na (hazard ratio = 1.42, 95% confidence interval = 1.28-1.58). The effect of moderate ascites was more prominent with a MELD score <21 (equal to 4.7 MELD units) or with a MELD-Na score <21 (equal to 3.5 MELD-Na units). Wait-list mortality was higher in patients with moderate ascites who were listed in high-demand, limited-supply regions (25.8% versus 17.5% at 1 year, P < 0.01). With the addition of moderate ascites, there was improvement in the overall risk model, particularly with a MELD score <21, as measured by the C index and integrated discrimination improvement. Moderate ascites informed risk prediction, particularly with a MELD score <21 and in high-demand, limited-supply regions. Under the MELD system, the presence of moderate ascites should prompt clinicians to consider strategies to expand access to transplantation, such as the use of extended donor liver grafts.

Figure 1

Kaplan Meier Curves of Survival by Degree of Ascites. Increasing volume of ascites was associated with increased mortality risk.

Figure 2

90-day Mortality Risk in Patients with and without Moderate Ascites. (a) In the presence of moderate ascites, mortality was increased across the MELD spectrum especially when MELD was less than 21. An additional 4.7 MELD units would adjust for the observed increase in mortality. (b) Mortality was similarly elevated across the MELDNa spectrum. In the presence of moderate ascites, an additional 3.5 MELDNa units would adjust for the observed increase in mortality.

Figure 2

90-day Mortality Risk in Patients with and without Moderate Ascites. (a) In the presence of moderate ascites, mortality was increased across the MELD spectrum especially when MELD was less than 21. An additional 4.7 MELD units would adjust for the observed increase in mortality. (b) Mortality was similarly elevated across the MELDNa spectrum. In the presence of moderate ascites, an additional 3.5 MELDNa units would adjust for the observed increase in mortality.

Figure 3

90-day Mortality Risk across Serum Sodium in Patients with and without Moderate Ascites. Moderate ascites is independently associated with mortality independent of serum sodium, especially among those with normal serum sodium.