Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases

Supported by the American Association for the Study of Liver Diseases. Dr. Lai is partially supported by R01 AG059183 and R21 AG067554. Srinivasan Dasarathy is partially supported by NIH RO1 GM119174; RO1 DK113196; P50 AA024333; RO1 AA021890; 3U01AA026976 ‐ 03S1; UO1 AA 026976; R56HL141744;UO1 DK061732; 5U01 DK062470‐17S2. Potential conflict of interest: Dr. Lai received grants from Axcella and Lipocine. Dr. Bernal advises Versantis. Purpose and Scope of This Practice Guidance This is the first American Association for the Study of Liver Diseases (AASLD) practice guidance on the management of malnutrition, frailty, and sarcopenia in patients with cirrhosis. This guidance represents the consensus of a panel of experts after a thorough review and vigorous debate of the literature published to date, incorporating clinical experience and common sense to fill in the gaps when appropriate. Our goal was to offer clinicians pragmatic recommendations that could be implemented immediately in clinical practice to target malnutrition, frailty, and sarcopenia in this population. This AASLD guidance document differs from AASLD guidelines, which are supported by systematic reviews of the literature, formal rating of the quality of the evidence and strength of the recommendations, and, if appropriate, meta‐analysis of results using the Grading of Recommendations Assessment Development and Evaluation system. In contrast, this guidance was developed by consensus of an expert panel and provides guidance statements based on formal review and analysis of the literature on the topics, with oversight provided by the AASLD Practice Guidelines Committee at all stages of guidance development. The AASLD Practice Guidelines Committee chose to perform a guidance on this topic because a sufficient number of randomized controlled trials (RCTs) were not available to support the development of a guideline. Definitions of Malnutrition, Frailty, and Sarcopenia and Their Relationship in Patients With Cirrhosis Cirrhosis is a major predisposing condition for the development of malnutrition, frailty, and sarcopenia. Multiple, yet complementary, definitions of these conditions exist in the published domain outside of the field of hepatology; but consensus definitions have not yet been established by the AASLD for patients with cirrhosis. Furthermore, there has been ambiguity related to operationalization of these constructs in clinical practice. To address this, we offer definitions of the theoretical constructs of malnutrition, frailty, and sarcopenia as commonly represented in all populations, partnered with operational definitions, developed by consensus, to facilitate pragmatic implementation of these constructs in clinical practice as applied to patients with cirrhosis (Table 1). Malnutrition is a clinical syndrome that results from “an imbalance (deficiency or excess) of nutrients that causes measurable adverse effects on tissue/body form (body shape, size, composition) or function, and/or clinical outcome.”(1) Key to this definition is the recognition that malnutrition represents a spectrum of nutritional disorders across the entire range of body mass index (BMI)—from underweight to obese. By this definition, malnutrition leads to adverse physical effects, which, in patients with cirrhosis, are commonly manifested phenotypically as frailty or sarcopenia. Frailty has most commonly been defined as a clinical state of decreased physiologic reserve and increased vulnerability to health stressors, a definition that has its roots in the field of geriatrics.(2) However, the weight of evidence available to date in patients with cirrhosis has focused predominantly on one component of frailty: physical frailty. Although this representation deviates somewhat from the classic “geriatric” definition of frailty as a global construct, physical frailty represents clinical manifestations of impaired muscle contractile function that are commonly reported by patients with cirrhosis such as decreased physical function, decreased functional performance, and disability. Sarcopenia has been defined by the European Working Group on Sarcopenia as “a progressive and generalized skeletal muscle disorder associated with an increased likelihood of adverse outcomes including falls, fractures, disability, and mortality,” combining both muscle mass and muscle strength or muscle performance in its definition.(3) However, the majority of studies in patients with cirrhosis have investigated sarcopenia using measures of muscle mass alone. Therefore, based on the evidence available to date on patients with cirrhosis, we have developed a consensus definition for operationalization of sarcopenia in patients with cirrhosis as the phenotypic manifestation of loss of muscle mass. Table 1 - Definitions for the Theoretical Constructs of Malnutrition, Frailty, and Sarcopenia and Consensus‐Derived Operational Definitions Applied to Patients with Cirrhosis Construct Theoretical Definitions Operational Definitions Malnutrition A clinical syndrome that results from deficiencies or excesses of nutrient intake, imbalance of essential nutrients, or impaired nutrient use( 4 ) An imbalance (deficiency or excess) of nutrients that causes measurable adverse effects on tissue/body form (body shape, size, composition) or function and/or clinical outcome( 1 ) Frailty A clinical state of decreased physiologic reserve and increased vulnerability to health stressors( 2 ) The phenotypic representation of impaired muscle contractile function Sarcopenia A progressive and generalized skeletal muscle disorder associated with an increased likelihood of adverse outcomes including falls, fractures, disability, and mortality( 3 ) The phenotypic representation of loss of muscle mass Although we have, for the purposes of this guidance, developed separate operational definitions for malnutrition, frailty, and sarcopenia, we acknowledge that these three constructs are interrelated and in practice are often recognized simultaneously in an individual patient. For example, a patient with cirrhosis who presents to clinic with severe muscle wasting might be described as “malnourished,” “frail,” and “sarcopenic,” each descriptor conveying similar information about the patient’s poor clinical condition and prognosis. Despite the overlap of these three constructs in clinical practice, there is value in understanding each as a separate entity as well as the relationship the three in to and for these we a for this relationship 1). are a number of that to malnutrition in patients with cirrhosis, which is to at the phenotypically as frailty and/or sarcopenia. 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