12. Frailty and Sarcopenia in the Selection of Candidates for Liver Transplantation
KeywordsLiver transplantationCandidate selectionFrailtySarcopeniaPrehabilitation
Perhaps the greatest responsibility of transplant hepatologists and surgeons is to evaluate and select appropriate candidates for liver transplantation. Deceased organ donors remain a precious resource of limited supply, and every effort must be made to avoid performing futile transplants in patients without the ability to recover and thrive posttransplant. Furthermore, the candidate pool for liver transplantation is becoming increasingly old, with associated comorbidity and debilitation. The median age at transplant in the USA has risen a decade in the past 15 years and will likely cross 60 in the coming years. Furthermore, the rise of alcohol-related liver disease and NASH-related cirrhosis as the leading indications for liver transplantation in the USA has increased the number of candidates with the significant challenges of malnutrition and associated substance abuse and associated obesity and metabolic syndrome, respectively.
In that context, novel tools for candidate selection are needed, particularly those that reflect global health and physiologic reserve. Accumulating evidence has suggested that frailty and sarcopenia may both serve as useful metrics for candidate selection, but application of these tools in a standardized and validated fashion has been limited. It is important to emphasize that frailty and sarcopenia, while often thought of as similar or interchangeable, are distinct metrics with different clinical implications. Frailty is clearly a functional construct, incorporating measures such as walking speed, grip strength, or chair stands that reflect muscle function in addition to muscle mass. Furthermore, frailty measures often include subjective measures of the patient experience, such as self-reported exhaustion, which suggest a patient’s experience of their global health status may also have an impact on clinical outcomes. Given the functional components, frailty measures have typically been applied only to ambulatory outpatients and may not apply to acutely ill inpatient candidates. Sarcopenia measured by imaging modalities offers objective and reproducible data about muscle mass and quality and therefore may be more broadly applicable across patient populations of varying acuity. However, current sarcopenia tools do not offer a functional component and therefore may not fully reflect an individual patient’s clinical presentation. It is best to think of these two metrics as distinct and complementary in the evaluation of candidates for liver transplantation.
Frailty Measures in Transplant Candidate Selection
The impact of frailty on outcomes in surgical candidates, acutely ill patients, and even patients with end-stage organ disease is well-established and fits with clinical intuition. However, frailty measurement has suffered from a lack of validated measurement tools, particularly those studied in specific populations. In general, functional assessments of frailty incorporate direct patient assessment, as opposed to other frailty scores derived from administrative data, patient reporting, or subjective clinician grading (Karnofsky Performance Status [KPS], activities of daily living/instrumental activities of daily living [ADLs/IADLs], clinical frailty score, Braden scale). In liver transplant candidates, a variety of functional measurement tools have been studied including 6-minute walk test, Fried frailty phenotype, the liver frailty index (LFI), short physical performance battery, and cardiopulmonary exercise testing . Of these available tools, the Fried frailty phenotype and the LFI appear to offer the most reliable performance in terms of predictive utility and clinical feasibility. The LFI, as developed and validated by Lai et al.,  has the additional advantages of minimal subjectivity and faster execution in clinical settings and should be the preferred measurement tool in the liver transplant candidate population.
Select frailty measurement tools in candidates for liver transplantation
Advantages in liver transplant population
Estimated time for assessment
Criteria for high frailty
Karnofsky Performance Score
Intuitive to clinicians and patients
Applicable even to critically ill patients
Well-associated with outcomes across patient populations
Difficulty with ≥2 ADLs
Liver frailty index
Objective, performance based
Applicable to outpatient setting
Easy to perform
6-minute walk test
Objective, performance based
No specialized equipment