Malnutrition, defined as deficiency, excess, or imbalance of nutrients, is a common complication in patients with liver disease, especially those with cirrhosis. Malnutrition may present as an isolated micronutrient deficiency, such as zinc deficiency, and it commonly presents as frailty and/or sarcopenia in patients with advanced liver disease. Patients with cirrhosis and/or alcohol-associated hepatitis should be assessed for malnutrition because it adversely affects patient outcomes including mortality, as well as waitlist and posttransplant outcomes among liver transplant candidates. The prevalence of malnutrition varies based on the method of assessment and disease severity, being higher in those with advanced liver disease. Among stable outpatients with cirrhosis, counseling should be done to eat small frequent meals, a night-time snack between 7 PM and 10 PM, and 2 or more cups of coffee daily. In selected patients with metabolic dysfunction-associated steatohepatitis, vitamin E 800 IU/d should be provided. Among hospitalized patients with cirrhosis, nutritional supplementation preferably by enteral route should be implemented in those with poor oral intake of daily requirements of proteins and/or calories. Protein intake should not be restricted including patients with decompensated cirrhosis and hepatic encephalopathy. A vegetable source of protein seems to be better tolerated than an animal source of protein in patients with hepatic encephalopathy. Branched chain amino acids augment the efficacy of lactulose and rifaximin in the treatment of hepatic encephalopathy. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the auspices of the American College of Gastroenterology Practice Parameters Committee.

With the advancement of world population aging, age-related sarcopenia (SP) imposes enormous clinical burden on hospital. Clinical research of SP in non-geriatric wards has not been appreciated, necessitating further investigation. However, observational studies are susceptible to confounders. Mendelian randomization (MR) can effectively mitigate bias to assess causality.

To investigate the correlation between SP and comorbidities in orthopedic wards, and subsequently infer the causality, providing a theoretical basis for developing strategies in SP prevention and treatment.

Logistic regression models were employed to assess the correlation between SP and comorbidities. The MR analysis was mainly conducted with inverse variance weighted, utilizing data extracted from the UK and FinnGen biobank (Round 9).

In the cross-sectional analysis, SP exhibited significant associations with malnutrition (P = 0.013) and some comorbidities, including osteoporosis (P = 0.014), body mass index (BMI) (P = 0.021), Charlson Comorbidity Index (CCI) (P = 0.006). The MR result also provided supporting evidence for the causality between SP and hypertension, osteoporosis and BMI. These results also withstood multiple sensitivity analyses assessing the validity of MR assumptions.

The result indicated a significant association between SP and BMI, CCI, malnutrition, and osteoporosis. We highlighted that SP and comorbidities deserved more attention in non-geriatric wards, urging further comprehensive investigation.

Sarcopenia and metabolic dysfunction associated steatotic liver disease (MASLD) are closely intertwined. Sarcopenia, traditionally a disease of the older adult and chronic disease population, has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD. They share similar risk factors of insulin resistance and physical inactivity. Given similar pathophysiology along the liver-muscle axis, sarcopenia has been studied as a risk factor for MASLD, and vice versa. Current research suggests a bidirectional relationship. Given the chronicity of MASLD as a chronic inflammatory liver disease, it can break down muscle mass and lead to sarcopenia, while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver. However, for the longest time, a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes. A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study. However, no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet. Future studies are needed to reach a consensus and reduce diagnostic variation. With similar pathophysiology and shared risk factors between the two diseases, future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

Sarcopenia is common in patients with liver cirrhosis and is an independent predictor of multiple clinical outcomes. Most studies to date have used a static assessment of sarcopenia. However, there is very limited data evaluating the temporal course of muscle area in cirrhosis. To bridge this gap in clinical studies, we performed a longitudinal analysis to evaluate the impact of changes in sarcopenia for cirrhotic patients.

Adult patients with clinically diagnosed liver cirrhosis who underwent at least 2 abdominal computed tomography (CT) scans in the hospital were enrolled. The interval between the two abdominal scans was 6 ± 1 months. Patients were categorized into persistent non-sarcopenia, new-onset sarcopenia, sarcopenia to non-sarcopenia, and persistent sarcopenia based on changes in sarcopenia. Kaplan-Meier method and Log-rank tests were used to separately compare unadjusted survival curves by different statuses of sarcopenia. Cox regression analysis was performed to assess the associations between different states of sarcopenia and overall mortality. The association between persistent non-sarcopenia and new-onset sarcopenia was analyzed by multivariate logistic regression analysis.

A total of 307 patients were included for analysis. At the second assessment, 10.10% (31/307) patients were new-onset sarcopenia, 27.69% (85/307) with persistent sarcopenia status, while 13.03% (40/307) patients with sarcopenia developed non-sarcopenia and 49.19% (151/307) with persistent non-sarcopenia status. The overall survival rate was significantly lower in the persistent sarcopenia and new-onset sarcopenia than in the non-sarcopenia group and sarcopenia to non-sarcopenia group (p < 0.001). Persistent sarcopenia (HR 5.799, 95%CI 1.563-21.521, p = 0.009) and new onset sarcopenia (HR 5.205, 95%CI 1.482-18.282, p = 0.010) were identified as poor prognostic factors for cirrhotic patients. The etiology of cirrhosis and the initial skeletal muscle mass were independent risk factors for new-onset sarcopenia.

Sarcopenia is a dynamically changing process in patients with cirrhosis. Persistent and new-onset sarcopenia were independently and robustly associated with overall survival.

The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.

This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.

The optimal cut-off values of L3-SMI were 39.50 cm 2 /m 2 for male patients and 33.06 cm 2 /m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P  = 0.012).

This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical decisions regarding patients' eligibility for critical care and transplantation. This, in turn, can guide the development of an individualized treatment plan for each patient with cirrhosis, with a focus on prioritizing exercise, proper nutrition, and appropriate treatment of hepatic complications as the primary lines of treatment. In this review, we aim to explore the topic of frailty in liver diseases, with a particular emphasis on pathophysiology, clinical assessment, and discuss strategies for preventing frailty through effective treatment of hepatic complications. Furthermore, we explore novel assessment and management strategies that have emerged in recent years, including the use of wearable technology and telemedicine.

As our population ages, the number of elderly patients with advanced chronic liver disease (ACLD) will increase. In this review we explore risk factors for liver injury, noninvasive assessment of liver disease, complications of cirrhosis, and management of frailty and sarcopenia in the older patient with ACLD.

Multiple guidelines regarding ACLD have been updated over the past few years. New cutoffs for FIB-4 and NAFLD (MASLD - Metabolic Dysfunction Associated Steatotic Liver Disease) fibrosis scores for elderly patients are being validated. Older patients with MASLD benefit from caloric restriction, exercise programs, and GLP-1 agonists. Patients with ACLD need to be screened for alcohol use disorder with modified scoring systems, and if positive, benefit from referral to chemical dependency programs. Carvedilol and diuretics may safely be used in the elderly for portal hypertension and ascites, respectively, with careful monitoring. Malnutrition, frailty, sarcopenia, and bone mineral disease are common in older patients with ACLD, and early intervention may improve outcomes. Early identification of ACLD in elderly patients allows us to manage risk factors for liver injury, screen for complications, and implement lifestyle and pharmacological therapy to reduce decompensation and death. Future studies may clarify the role of noninvasive imaging in assessing liver fibrosis in the elderly and optimal interventions for nutrition, frailty, sarcopenia, bone health in addition to reevaluation of antibiotic prophylaxis for liver conditions with rising antibiotic resistance.

Reduced muscle mass is linked to poor outcomes in both inpatients and outpatients, highlighting the importance of muscle mass assessment in clinical practice. However, laboratory methods to assess muscle mass are not yet feasible for routine use in clinical practice because of limited availability and high costs.

This work aims to review the literature on muscle mass prediction by anthropometric equations in adults or older people.

The following databases were searched for observational studies published until June 2022: MEDLINE, Embase, Scopus, SPORTDiscus, and Web of Science.

Of 6437 articles initially identified, 63 met the inclusion criteria for this review. Four independent reviewers, working in pairs, selected and extracted data from those articles.

Two studies reported new equations for prediction of skeletal muscle mass: 10 equations for free-fat mass and lean soft tissue, 22 for appendicular lean mass, 7 for upper-body muscle mass, and 7 for lower-body muscle mass. Twenty-one studies validated previously proposed equations. This systematic review shows there are numerous equations in the literature for muscle mass prediction, and most are validated for healthy adults. However, many equations were not always accurate and validated in all groups, especially people with obesity, undernourished people, and older people. Moreover, in some studies, it was unclear if fat-free mass or lean soft tissue had been assessed because of an imprecise description of muscle mass terminology.

This systematic review identified several feasible, practical, and low-cost equations for muscle mass prediction, some of which have excellent accuracy in healthy adults, older people, women, and athletes. Malnourished individuals and people with obesity were understudied in the literature, as were older people, for whom there are only equations for appendicular lean mass.

PROSPERO registration number CRD42021257200.

Frailty is a decline in functional reserve across multiple physiological systems. A key component of frailty is sarcopenia, which denotes a loss of skeletal muscle mass and impaired contractile function that ultimately result in physical frailty. Physical frailty/sarcopenia are frequent and contribute to adverse clinical outcomes before and after liver transplantation. Frailty indices, including the liver frailty index, focus on contractile dysfunction (physical frailty), while cross-sectional image analysis of muscle area is the most accepted and reproducible measure to define sarcopenia. Thus, physical frailty and sarcopenia are interrelated. The prevalence of physical frailty/sarcopenia is high in liver transplant candidates and these conditions have been shown to adversely impact clinical outcomes including mortality, hospitalisations, infections, and cost of care both before and after transplantation. Data on the prevalence of frailty/sarcopenia and their sex- and age-dependent impact on outcomes are not consistent in patients on the liver transplant waitlist. Physical frailty and sarcopenic obesity are frequent in the obese patient with cirrhosis, and adversely affect outcomes after liver transplantation. Nutritional interventions and physical activity remain the mainstay of management before and after transplantation, despite limited data from large scale trials. In addition to physical frailty, there is recognition that a global evaluation including a multidisciplinary approach to other components of frailty (e.g., cognition, emotional, psychosocial) also need to be addressed in patients on the transplant waitlist. Recent advances in our understanding of the underlying mechanisms of sarcopenia and contractile dysfunction have helped identify novel therapeutic targets.

With the development of many international guidelines, research on sarcopenia has increased rapidly, showing that sarcopenia is predictive of adverse outcomes, including increased mortality and impaired mobility, in patients with cirrhosis. The purpose of this article is to review the current evidence concerning the epidemiology, diagnosis, management and predictive value of sarcopenia on the prognosis of patients with cirrhosis.

Sarcopenia is a frequent and lethal complication of cirrhosis. Currently, abdominal computed tomography imaging is the most commonly used method to diagnose sarcopenia. In clinical practice, assessing muscle strength and physical performance, such as by measuring handgrip strength and gait speed, is of increasing interest. In addition to the necessary pharmacological therapy, adequate intake of protein, energy and micronutrients, as well as regular moderate-intensity exercise, can help to minimize sarcopenia. Sarcopenia has been shown to be a strong predictor of prognosis in patients with severe liver disease.

A global consensus is needed on the definition and operational parameters for the diagnosis of sarcopenia. Further research should focus on developing standardized screening, management and treatment protocols for sarcopenia. Adding sarcopenia to existing models may better exploit the effect of sarcopenia on prognosis in patients with cirrhosis, which should be investigated further.

Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.

Sarcopenia is an underdiagnosed and understudied complication of cirrhosis, especially in patients not undergoing liver transplantation.

To evaluate the prevalence and prognostic impact of radiological sarcopenia in non-transplanted cirrhotic patients.

Longitudinal retrospective study including cirrhotic patients explored by an abdominal CT scan, over a period of 6 years, in a single gastroenterology department in Tunisia. Sarcopenia was defined according to transversal psoas muscle thickness normalized to height (TPMT/h) in the sagittal CT slice. Two groups were defined: Group 1 with sarcopenia (TPMT/h <16.8mm/m); and Group 2 without sarcopenia (TPMT/h ≥16.8mm/m).

Seventy patients were included (mean age=62 years). The mean MELD score was 12.81 and the mean TPMT/h of 13.56 mm/m. Forty-four patients were sarcopenic (63%). When included, the 2 groups' baseline characteristics were comparable except for women predominance and refractory ascites in group 1. After an average of 21-month follow-up, sarcopenia was associated with a higher number of complications per patient (p=0.013) and a longer average hospital stay duration per patient (p=0.001). Overall survival was significantly decreased in sarcopenic patients (p=0.035). Survival rates at 6 months, 1 year, and 2 years were respectively 42%, 30%, and 24% in Group 1 versus 67%, 40%, and 27% in Group 2. Sarcopenia was an independent factor of mortality in multivariate analysis (OR=2.5; 95% IC [1.02-6.16]; p=0.045).

Sarcopenia is frequent and an independent poor prognostic factor in cirrhosis. TPMT/h is an easy and often available method for sarcopenia diagnosis.

Sarcopenia leads to complications (infections, hepatic encephalopathy and ascites) and poor overall survival in patients with cirrhosis, in which the phenotypic presentation is loss of muscle mass. This study aimed to reveal the metabolic profile and identify potential biomarkers in cirrhotic patients with hepatitis B virus and muscle mass loss.

Twenty decompensated cirrhotic patients with HBV and muscle mass loss were designated Group S; 20 decompensated cirrhotic patients with HBV and normal muscle mass were designated Group NS; and 20 healthy people were designated Group H. Muscle mass loss was defined as the skeletal muscle mass index less than 46.96 cm²/m² for males and less than 32.46 cm²/m² for females. Gas chromatography-mass spectrometry was used to explore the distinct metabolites and pathways in the three groups.

Thirty-seven metabolic products and 25 associated metabolic pathways were significantly different in the Group S patients from Group NS patients. Strong predictive value of 11 metabolites (inosine-5'-monophosphate, phosphoglycolic acid, D-fructose-6-phosphate, N-acetylglutamate, pyrophosphate, trehalose-6-phosphate, fumaric acid, citrulline, creatinine, (r)-3-hydroxybutyric acid, and 2-ketobutyric acid) were selected as potential biomarkers in Group S patients compared with Group NS patients. Two pathways may be associated with loss of muscle mass in patients with liver cirrhosis: amino acid metabolism and central carbon metabolism in cancer.

Seventy differential metabolites were identified in patients who have liver cirrhosis and loss of muscle mass compared with patients who have cirrhosis and normal muscle mass. Certain biomarkers might distinguish between muscle mass loss and normal muscle mass in HBV-related cirrhosis patients.

Sarcopenia is strongly associated with poor outcome in cirrhosis. There are little prospective data that sarcopenia influences outcomes in critically ill cirrhotics (CICs). Computed tomography (CT) is the gold standard for sarcopenia assessment in the intensive care unit (ICU), as it is independent of hydration status.

This study aims to assess the prevalence of sarcopenia and study its impact on clinical outcomes in CICs.

In this prospective observational study, CICs admitted to the liver ICU were enrolled, if meeting inclusion (age 18-70 years, abdominal CT scan within three months before ICU admission) and exclusion criteria (survival likely to be <24 h, coexisting chronic diseases). Clinical, hemodynamic, biochemical, and nutritional parameters, including length of stay (LOS), duration of mechanical ventilation (MV), development of new-onset infections (NOI), incidence of new-onset acute kidney injury (AKI), and overall survival, were recorded. CT images at the L3 level were analyzed using Slice-O-Matic V4.3 software to assess the skeletal muscle index (SMI) expressed as skeletal muscle area (cm²)/height (m²). Sarcopenia was defined if SMI was <50 cm²/m² - males and <39 cm²/m² - females. Data were analyzed using SPSS version 22.

Altogether 111 patients (M-83.8%; age 48.4±11.3 years; etiology: Alcohol - 56 [50.5%], non-alcoholic steatohepatitis - 27 [24.3%], viral - 12 [10.8%], and others - 16 [14.4%]; Child-Turcotte-Pugh - 11.9±1.8; model for end-stage liver disease - 27.8±7.3; sequential organ failure assessment - 10.5±4.1; APACHE - 23±8; and MV - 54 [48.6%]) were enrolled. Of these, 76 (68.5%) were sarcopenic and 35 (31.5%) non-sarcopenic. Sarcopenic CICs had higher overall mortality (72.4%) compared to non-sarcopenics (40%) (P=0.001, OR [95% CI] - 3.93 [1.69-9.12]), and higher prevalence of sepsis at ICU admission (53.9% vs. 31.4%, P=0.027, OR [95% CI] - 1.7 [1.0-2.92]) than non-sarcopenics. LOS, duration of MV, incidence of NOI, and development of new-onset AKI were comparable between groups. Multivariate binary logistic regression showed that sarcopenia, sepsis, and APACHE II score were independently associated with mortality.

Two-thirds of CICs have sarcopenia at ICU admission, making them 1.7 times more susceptible to sepsis and increasing the risk of mortality by almost 4-fold in the ICU.

Almost 70% of patients with chronic liver disease admitted to the ICU have low muscle mass (sarcopenia). The presence of sarcopenia per se makes them highly prone to infections and increases the chances of death by almost 4-fold; thus, highlighting the importance of nutrition optimization in this patient group.

Ammonia is a cytotoxic molecule generated during normal cellular functions. Dysregulated ammonia metabolism, which is evident in many chronic diseases such as liver cirrhosis, heart failure, and chronic obstructive pulmonary disease, initiates a hyperammonemic stress response in tissues including skeletal muscle and in myotubes. Perturbations in levels of specific regulatory molecules have been reported, but the global responses to hyperammonemia are unclear. In this study, we used a multiomics approach to vertically integrate unbiased data generated using an assay for transposase-accessible chromatin with high-throughput sequencing, RNA-Seq, and proteomics. We then horizontally integrated these data across different models of hyperammonemia, including myotubes and mouse and human muscle tissues. Changes in chromatin accessibility and/or expression of genes resulted in distinct clusters of temporal molecular changes including transient, persistent, and delayed responses during hyperammonemia in myotubes. Known responses to hyperammonemia, including mitochondrial and oxidative dysfunction, protein homeostasis disruption, and oxidative stress pathway activation, were enriched in our datasets. During hyperammonemia, pathways that impact skeletal muscle structure and function that were consistently enriched were those that contribute to mitochondrial dysfunction, oxidative stress, and senescence. We made several novel observations, including an enrichment in antiapoptotic B-cell leukemia/lymphoma 2 family protein expression, increased calcium flux, and increased protein glycosylation in myotubes and muscle tissue upon hyperammonemia. Critical molecules in these pathways were validated experimentally. Human skeletal muscle from patients with cirrhosis displayed similar responses, establishing translational relevance. These data demonstrate complex molecular interactions during adaptive and maladaptive responses during the cellular stress response to hyperammonemia.