Sarcopenic obesity in patients awaiting liver transplant: Unique challenges for nutritional recommendations

Sarcopenic obesity increases the risk of mortality in patients with liver disease awaiting liver transplantation and in the post-transplant period.Nutrition recommendations for individuals with sarcopenia differ from recommendations for patients with obesity or sarcopenic obesity.While these nutrition guidelines have been established in non-cirrhotic patients,established guidelines for liver transplant candidates with sarcopenic obesity are lacking.In this paper,we review existing literature on sarcopenic obesity in patients with chronic liver disease and address opportunities to improve nutritional counseling in patients awaiting liver transplantation.

Sarcopenic obesity:recent consensus and clinical implications in patients with chronic liver disease

Sarcopenia and obesity are two major public health concerns,particularly in the elderly population.These conditions have a significant impact on both the individual’s health and quality of life.Sarcopenia is defined as a loss of muscle mass,strength,and function physiologically present with aging,while obesity is an excessive accumulation of body fat.While these conditions are often considered separately,there is growing recognition that they frequently coexist,may synergistically enhance one another,leading to an increased risk of various chronic diseases and mortality.Sarcopenic obesity(SO)is the term utilized to define the simultaneous occurrence of sarcopenia and obesity(1).Since recently,the lack of common diagnostic criteria for SO has made it difficult to diagnose and manage this condition effectively.

Proposal of definition and diagnostic criteria for sarcopenic obesity by ESPEN and EASO

In the last decade,many investigators including us have reported the negative impact of preoperative sarcopenia or low skeletal muscle mass on outcomes after surgery including hepato-biliary-pancreatic(HBP)surgery such as liver transplantation,liver surgery,biliary surgery,and pancreatic surgery(1-5).In addition to low skeletal muscle mass,the abnormality of body compositions,decreased muscle quality and visceral obesity,has been clarified to be also negatively associated with poor outcomes after HBP surgery(2-5).Consequently,it was easily supposed that co-existence of sarcopenia and obesity,called sarcopenic obesity(SO),had more strong negative impact on outcomes.Actually,not a few studies have demonstrated negative clinical impact of SO on outcomes after HBP surgery using various definitions for SO(6-10).We reported that patients with SO,defined by low skeletal muscle mass with high visceral fat to subcutaneous fat ratio evaluated by preoperative computed tomography(CT)image,had significant worse survival than non-sarcopenia patients and patients with sarcopenia only after liver transplantation,hepatic resection,and pancreatic resection(6-9).

Sarcopenic obesity in liver disease: Handling both sides of the penny

Skeletal muscle and fat tissue show distinct pathophysiological roles and pivotal functions.The culmination of muscle wasting and fat accumulation represents an opposite terminal of each state.Specifically,this situation has been designated as sarcopenic obesity.However,sarcopenic obesity still lacks a unanimous definition,diagnostic criteria,and generalized modalities for assessment in the context of versatile liver diseases.Moreover,the underpinning mechanisms by which a combination of abnormal skeletal muscle and fat tissue leads to the progression of liver disease and impairs health‐related consequences are still elusive.Additionally,the interplay between skeletal muscle and fat,and the driving factors that shift different body compositions are not well understood.Therefore,in this review,we discuss skeletal muscle and fat components,with the purpose of conceptualization,as well as interpret their roles in liver diseases.We focus on the definitions,diagnostic criteria,and currently available measurements for sarcopenic obesity in the literature.We comprehensively discuss recent data and evidence regarding the potential role of sarcopenic obesity in the development and progression of numerous liver diseases and associated conditions,including nonalcoholic fatty liver disease,chronic viral hepatitis,cirrhosis,and liver transplantation.Furthermore,explicit information related to the pathogenesis of sarcopenic obesity from basic research is also provided in this narrative review.Finally,we discuss,from the clinical perspective of view,how to manage sarcopenic obesity using nutritional,physical,and pharmacological methods.

Metabolic-associated fatty liver disease and sarcopenia:A double whammy

The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

Approaching the Sarcopenic Patient with Nonalcoholic Steatohepatitis-related Cirrhosis

Sarcopenia is a well-known complication of chronic liver disease(CLD),and it is almost always observed in patients with cirrhosis,at least in those with decompensated disease.Since nonalcoholic fatty liver disease(NAFLD),recently renamed metabolic dysfunction-associated steatotic liver disease(MASLD),is becoming the leading cause of end-stage liver disease,a new scenario characterized by the frequent coexistence of NAFLD,obesity,and sarcopenia is emerging.Although it is not yet resolved whether the bidirectional relationship between sarcopenia and NAFLD subtends causal determinants,it is clear that the interaction of these two conditions is associated with an increased risk of poor outcomes.Notably,during the course of CLD,deregulation of the liver-muscle-adipose tissue axis has been described.Unfortunately,owing to the lack of properly designed studies,specific therapeutic guidelines for patients with sarcopenia in the context of NAFLD-related CLD have not yet been defined.Strategies aimed to induce the loss of fat mass together with the maintenance of lean body mass seem most appropriate.This can be achieved by properly designed diets integrated with specific nutritional supplementations and accompanied by adequate physical exercise.Future studies aiming to add to the knowledge of the correct assessment and approach to sarcopenia in the context of NAFLD-related CLD are eagerly awaited.

Sarcopenia and non-alcoholic fatty liver disease:Is there a relationship?A systematic review

AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) in adult patients with sarcopenia.METHODS Randomized clinical trials,cross-sectional or cohort studies including adult patients(over 18 years) with sarcopenia were selected.The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients.In the screening process,44 fulltext articles were included in the review and 41 studies were excluded.RESULTS Three cross-sectional studies were included.The authors attempted to perform a systematic review,but due to the differences between the studies,a qualitative synthesis was provided.The diagnosis of NAFLD was made by non-invasive methods(image methods or any surrogate markers) in all three evaluated studies.All the studies suggested that there was an independent association between sarcopenia and NAFLD.CONCLUSION Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.