Leveraging Frailty to Mitigate Sex-Based Disparities in Access to Liver Transplant

Abstract

For patients with end-stage liver disease (ESLD), liver transplant is the only life-saving therapy. Given the ongoing organ shortage, a Model for End-stage Liver Disease (MELD)-based allocation was introduced in 2002 to ensure that the sickest patients were offered transplant first. MELD is a calculation based on objective laboratory data, including serum creatinine level, associated with 90-day mortality among patients with ESLD. Despite the goal of defining an objective, equitable measure of disease severity, MELDbased allocation inadvertently introduced sex-based disparities in liver transplant, with women experiencing higher wait list mortality and lower likelihood of transplant compared with men. 1 These sex-based disparities may be the result of including serum creatinine level as a measure of renal dysfunction in MELD. Importantly, serum creatinine level has been demonstrated to vary significantly based on differences in muscle mass, and not surprisingly, women tend to have lower serum creatinine levels than men, despite having the same measured kidney function (measured glomerular filtration rate). Attempts to account for this biological difference in MELD-based allocation (eg, substituting measured glomerular filtration rate for serum creatinine level) have not been widely embraced, because they would require additional testing beyond simple blood draws and be difficult to update in real time. 2 The search for alternative measures that can be easily incorporated into existing allocation algorithms is greatly needed. Frailty may be the answer. It has been identified as a risk factor for wait list mortality and is associated with declining lean body mass. 3

Frailty and mini dental implants

“…Again, if 1–2 criteria are met, then there is intermediate frailty, and if three or more are met, then there is a diagnosis of frailty 5,6 . Women with cirrhosis have a higher frailty rate than men with similar disease severity 7,8 . There are other criteria to be used to diagnose frailty, but there is no agreed‐upon standard.…”

“… 5 , 6 Women with cirrhosis have a higher frailty rate than men with similar disease severity. 7 , 8 There are other criteria to be used to diagnose frailty, but there is no agreed‐upon standard.…”

Correcting the sex disparity in MELD-Na

“…To equalize the 90-day without-transplant survival rate based on our 3.2.1 above, women had their MELD-Na score shifted according to Table 3. There are some scores for women under MELD-Na-Shift which cannot be obtained, because after shifting there are no longer any women at that MELD-Na score (e.g., 16).…”

“…There have been recent calls to develop and study policy changes to mitigate sex disparities in liver transplantation 15,16 . An early approach was to correct serum creatinine based on the modification of diet in renal disease (MDRD) formula for estimated GFR (eGFR) 7 .…”

“…There have been recent calls to develop and study policy changes to mitigate sex disparities in liver transplantation. 15,16 An early approach was to correct serum creatinine based on the modification of diet in renal disease (MDRD) formula for estimated GFR (eGFR). 7 This resulted in 65% of women having an increase of 2 or 3 points under the MDRD correction, but unfortunately this correction to MELD was no better than MELD at predicting 3-, 6-, 9-, or 12-month mortality for women, 10 with similar results in subsequent studies of this approach.…”