Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre-and post-liver transplantation. The pathogenesis of sarcopenia is multifactorial and results from an imbalance between protein synthesis and breakdown. Nutritional, metabolic, and biochemical abnormalities seen in chronic liver disease alter whole body protein homeostasis. Hyperammonemia, increased autophagy, proteasomal activity, lower protein synthesis, and impaired mitochondrial function play an important role in muscle depletion in cirrhosis. Factors including cellular energy status, availability of metabolic substrates (e.g., branched-chain amino acids), alterations in the endocrine system (insulin resistance, circulating levels of insulin, insulin-like growth factor-1, corticosteroids, and testosterone), cytokines, myostatin, and exercise are involved in regulating muscle mass. A favored atrophy of type II fasttwitch glycolytic fibers seems to occur in patients with cirrhosis and sarcopenia. Identification of muscle biological abnormalities and underlying mechanisms is required to plan clinical trials to reverse sarcopenia through modulation of specific mechanisms. Accordingly, a combination of nutritional, physical, and pharmacological interventions might be necessary to reverse sarcopenia in cirrhosis. Moderate exercise should be combined with appropriate energy and protein intake, in accordance with clinical guidelines. Interventions with branched chain amino acids, testosterone, carnitine, or ammonia-lowering therapies should be considered individually. Various factors such as dose, type, duration of supplementations, etiology of cirrhosis, amount of dietary protein intake, and compliance with supplementation and exercise should be the focus of future large randomized controlled trials investigating both prevention and treatment of sarcopenia in this patient population.

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Malnutrition is a common complication in patients with end‐stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre‐ and post‐LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre‐LT sarcopenia, pre‐LT sarcopenic obesity (SO), post‐LT sarcopenia, and post‐LT SO were 14%‐78%, 2%‐42%, 30%‐100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre‐LT sarcopenia is associated with higher wait‐list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre‐ and post‐LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD.

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Background Identifying children at malnutrition risk on admission to hospital is considered best practice; however, nutrition screening in pediatric populations is not common. The aim of this study was to determine which screening tool is able to identify children with malnutrition on admission to hospital. Methods A nurse administered 2 pediatric nutrition screening tools, Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) and Pediatric Nutrition Screening Tool (PNST) to patients admitted to medicine and surgery units (n = 165). The Subjective Global Nutritional Assessment (SGNA) was then completed by a dietitian, blinded to the results of the screens. Sensitivity, specificity, and κ were calculated for both screening tools against the SGNA. A receiver operating characteristic (ROC) curve assessed alternate cutoffs for each tool. Length of hospital stay (LOS) was used to assess prospective validity. Results Using the recommended cutoffs, the sensitivity of STRONGkids was 89%, specificity 35%, and κ 0.483. The sensitivity of PNST was 58%, specificity 88%, and κ 0.601. Using adjusted cutoffs, PNST's sensitivity improved to 87%, specificity 71%, and κ 0.681, and STRONGkids specificity improved to 61%, sensitivity 80%, and κ 0.5. Children identified at nutrition risk had significantly longer LOS (P < 0.05). Conclusion This study showed neither tool was appropriate for clinical use based on published cutoffs. By adjusting the cutoffs using ROC curve analysis, both tools improved overall agreement with the SGNA without significantly impacting the prospective validity. PNST with adjusted cutoffs is the most appropriate for clinical use in this population.

Summary Background Recent advances in evaluation of body composition show body mass index to be inadequate in differentiating between body compartments in cirrhosis. Given the limitations of body mass index, body composition evaluation using computed tomography has been increasingly used as a non‐invasive clinical tool with prognostic value. Another factor influencing prognosis includes sex‐specific differences in body composition that are seen in cirrhosis. Aim To review current knowledge regarding the frequency and clinical implications of abnormal body composition features in cirrhosis. Methods We searched PubMed database and limited the literature search to full‐text papers published in English. Studies using inappropriate landmarks or demarcation of body composition components on computed tomography images were eliminated. Results Sarcopenia is a well established factor affecting morbidity and mortality in cirrhosis. Other important body composition components that have been overlooked thus far include subcutaneous adipose tissue and visceral adipose tissue. Female patients with cirrhosis and low subcutaneous adiposity have a higher risk of mortality, whereas male patients with high visceral adiposity have a higher risk of hepatocellular carcinoma and recurrence following liver transplantation. Increased adipose tissue radiodensity has been associated with risk of decompensation and mortality. Conclusions Further evaluation of body composition abnormalities may help with development of targeted therapeutic strategies and improve outcome in patients with cirrhosis. Moreover, recognition of these abnormalities could improve prioritisation for liver transplantation as our current method based solely on liver function might lead to risk misclassification.

SummaryBackgroundVitamin D deficiency has been implicated in the outcome of chronic liver disease.AimTo determine the frequency of severe vitamin D deficiency in autoimmune hepatitis (AIH), assess its association with treatment non‐response, and evaluate the relationship between vitamin D status and liver‐related mortality and need for transplantation.MethodsTwo hundred and nine patients were evaluated by liver tissue examination at presentation. Serum vitamin D levels were determined, and serum levels <25 nmol/L (10 ng/mL) were considered severely deficient. Treatment non‐response was defined as non‐normalised aspartate aminotransferase/alanine aminotransferase and immunoglobulin G levels during conventional immunosuppressive therapy. Univariate and multivariate analyses were performed using binary logistic regression and Cox proportional hazards model.ResultsThe mean vitamin D level was 60 ± 38 nmol/L (range, 3‐263 nmol/L), and 42 patients (20%) had severe vitamin D deficiency. Treatment non‐response was more common in patients with severe vitamin D deficiency than in patients without (59% vs 41%, P = 0.04). Severe vitamin D deficiency was also independently associated with a higher risk of developing cirrhosis (HR 3.40; 95% CI 1.30‐8.87, P = 0.01) and liver‐related mortality or requirement for liver transplantation (LT; HR 5.26, 95% CI, 1.54‐18.0, P = 0.008). Patients with persistent severe deficiency following vitamin D supplementation continued to have poor outcomes.ConclusionsSevere vitamin D deficiency is associated with treatment non‐response, progression to cirrhosis, and liver‐related death or need for LT. Severe vitamin D deficiency is a prognostic biomarker in AIH.

Cirrhosis is the most common indication for liver transplantation (LT) worldwide. Malnutrition is present in at least two-thirds of patients with cirrhosis awaiting LT. It negatively impacts survival, quality of life, and the ability to respond to stressors, such as infection and surgery. Muscle wasting or sarcopenia is the most objective feature of chronic protein malnutrition in cirrhosis, and this condition is associated with increased morbidity and mortality before and after LT. In addition to its objectivity, muscularity assessment with cross-sectional imaging studies is a useful marker of nutritional status in LT candidates, as sarcopenia reflects a chronic decline in the general physical condition, rather than acute severity of the liver disease. Despite the high prevalence and important prognostic role, malnutrition and sarcopenia are frequently overlooked because standards for nutritional assessment are lacking and challenges such as fluid retention and obesity are prevalent. In this review, current diagnostic methods to evaluate malnutrition, including muscle abnormalities in cirrhosis, are discussed and current knowledge regarding the incidence and clinical impact of malnutrition in cirrhosis and its impact after LT are presented. Existing and potential novel therapeutic strategies for malnutrition in cirrhosis are also discussed, emphasizing the treatment of muscle wasting in the LT candidate in an effort to improve survival while waiting for LT and to reduce morbidity and mortality after LT.Liver Transplantation 23 1451-1464 2017 AASLD.