Measurements matter: Assessing outcomes in “lean” patients with nonalcoholic fatty liver disease awaiting liver transplantation

Nonalcoholic fatty liver disease (NAFLD) is among the most common and fastest rising indication for liver transplantation.¹ These patients are often older with more acquired comorbidities. Accordingly, challenges to their transplant candidacy, waitlist survival, and posttransplant outcomes can include their obesity, sarcopenia, and overall frailty. Managing these issues is frequently a paradox, especially in patients we ask to lose weight but increase muscle mass. If we define our goals for such interventions by weight alone, we may be missing the point.

In this issue of Liver Transplantation, Ochoa‐Allemant and colleagues present a study of waitlist and posttransplant outcomes of lean patients with NAFLD.² The authors used the United Network for Organ Sharing (UNOS) database to determine the association between body mass index (BMI) and waitlist removal and death as well as weight changes while on the waiting list and the association with all‐cause mortality and graft failure. Overall, they found that lean patients (those with a normal BMI [18.5–24.9 kg/m²]) suffered 26% greater waitlist removal compared with patients with Class I obesity (BMI, 30–34.9 kg/m²). Those who stayed lean while on the waiting list had a 61% higher all‐cause mortality rate and 57% greater graft loss rate than stable patients who were obese. Patients who can gain weight (BMI increase >3 kg/m²) had lower all‐cause mortality and graft failure compared with those who were stable.

These results must be taken in the context of the information available in the UNOS database. Metrics such as weight and BMI are available, but an objective assessment of frailty is not (yet). Interestingly, those with a normal BMI were more likely to have ascites and had worse overall functional status (a subjective assessment of the amount of assistance a patient requires) compared with patients with Class I obesity. This suggests that this group of patients with a normal BMI had lower proportional muscle mass and were frailer than their obese counterparts.

This study adds to our collective knowledge by further shining a light on the concept of frailty and its critical importance to patient survival on the liver transplantation waiting list and its connection to posttransplant outcomes. We should be cautious, however, to extrapolate these data on patients on the waiting list with a normal BMI or who are lean who also have ascites and decreased functional status and apply them to patients with NAFLD with a normal BMI; that is, the “lean” patient with precirrhosis NAFLD is not necessarily the “lean” patient on the waiting list with decompensated NAFLD.

In July 2022, stakeholders from around the world met in Chicago, IL, to determine if the medical profession could agree on a better name for NAFLD. There is a need for better nomenclature than a “non” disease using terminology that is accurate and not stigmatizing to patients, such as the terms “fatty” and “alcoholic” are for many. In the same spirit, we should strive for a more accurate term than lean. Although we understand that lean in this context means not overweight or obese, a normal BMI is what we really mean. However, should we use BMI at all to describe a population of patients with decompensated cirrhosis? What does BMI really tell us in the patient with edema or ascites? What does BMI mean in the clinical setting of sarcopenia? Lai and colleagues have used the liver frailty index to show that worsening frailty is associated with death or delisting for all patients with cirrhosis independent of the baseline Model for End‐Stage Liver Disease–Sodium score.³ This metric, although composed of some self‐reported/subjective components,⁴ gives us better granularity and insight into patient frailty than “normal BMI” or the descriptor “lean” and should be the metric for liver transplantation outcomes research moving forward. In sum, the crux of what Ochoa‐Allemant and colleagues are really telling us is that frailty is the true risk factor for poor waitlist and posttransplant outcomes in patients with NAFLD, but we lack the appropriate objective metric to analyze this patient characteristic in current administrative datasets.