12. Frailty and Sarcopenia in the Selection of Candidates for Liver Transplantation

Christopher J. Sonnenday¹

(1)

Department of Surgery, University of Michigan, Ann Arbor, MI, USA

Christopher J. Sonnenday

Email: csonnend@umich.edu

Keywords

Liver 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

Measurement

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 [6]. 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., [4] 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.

One challenge particularly relevant to the liver transplant candidate pool is the lack of validated frailty measurement tools in the acutely ill and/or inpatient setting. Acute illness, exacerbated by hepatic encephalopathy and other metabolic derangements, can undermine the ability to produce reliable measurements of frailty such as grip strength, chair stands, or walking speed. In this setting, there may be a greater role for clinician-derived subjective measurement scales such as the Karnofsky Performance Status (KPS) for more acute risk stratification. However, such measures only offer reliable prediction of short-term outcomes (inhospital outcomes, risk for readmission) and may not offer any longitudinal value in the end-stage liver disease population where frequent readmissions and acute decompensation episodes are common. It may be reasonable for individual centers to adopt a battery of tools to assess frailty across different settings and patient populations, such as LFI, KPS, ADLs/IADLs, and 6-minute walk test. There is value in choosing a consistent and parsimonious number of tools to assess frailty, such that providers become familiar with the interpretation of individual values and their changes over time in different patients and clinical scenarios (Table 12.1).

Table 12.1

Select frailty measurement tools in candidates for liver transplantation

Tool	Advantages in liver transplant population	Estimated time for assessment	Populations studied	Criteria for high frailty
Karnofsky Performance Score	Intuitive to clinicians and patients Applicable even to critically ill patients Low cost Fast	<10 seconds	Inpatient Outpatient	0–40
ADLs/IADLs	Patient reported No cost Well-associated with outcomes across patient populations	3–4 minutes	Inpatient Outpatient	Difficulty with ≥2 ADLs
Liver frailty index	Objective, performance based Applicable to outpatient setting Easy to perform	<10 minutes	Outpatient	≥4.5
6-minute walk test	Objective, performance based Continuous scale No specialized equipment	~6 minutes	Outpatient	<250 m