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 fast-twitch 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.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Up to one third of individuals with NAFLD will develop nonalcoholic steatohepatitis (NASH), which ...is associated with progression to cirrhosis and is rapidly becoming the leading indication for liver transplantation. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass, strength, and function. It is observed in up to 60% of patients with end‐stage liver disease and portends a poor prognosis. Recent studies have shown that sarcopenia is a novel risk factor for developing NAFLD. Pathophysiological mechanisms relating sarcopenia and NASH may include insulin resistance (IR) and increased inflammation. IR leads to accumulation of triglycerides in both muscle tissue and the liver. It also exacerbates proteolysis and leads to muscle depletion. Chronic inflammation leads to liver injury and progression of fibrosis. The inflammatory milieu also stimulates protein catabolism. Viewing skeletal muscle as an endocrine organ that secretes various salutary myokines may help us understand its role in the development of steatosis. A better understanding of the pathophysiology will aid in developing physical and pharmacological therapeutic interventions. In this review, we will explore the complex inter‐relationships between sarcopenia and NASH. We will discuss the impact of sarcopenia in patients with NASH and therapeutic options for the management of sarcopenia. (Hepatology 2017;66:2055–2065)
Sarcopenia is a common complication of cirrhosis and is defined as a progressive and generalized loss of skeletal muscle mass, strength, and function. Sarcopenia is associated with poor prognosis and ...increased mortality. How sarcopenia and muscle wasting relate to such poor outcomes requires looking beyond the overt muscle loss and at this entity as a systemic disease that affects muscles of vital organs including cardiac and respiratory muscles. This review explores the pathophysiological pathways and mechanisms that culminate in poor outcomes associated with sarcopenia. This provides a launching pad to identify potential targets for therapeutic intervention and optimization to improve patient outcomes.
Abstract Introduction Dysphagia, or swallowing impairment, is a growing concern in dementia and can lead to malnutrition, dehydration, weight loss, functional decline, and fear of eating and drinking ...as well as a decrease in quality of life (QOL). Objective The aim of this article is to do a systematic review of the literature to determine the patterns of swallowing deficits in different types of dementia and to look at the usefulness of different diagnostic and management strategies. Methods An electronic literature search was done using five electronic databases from 1990 to 2011. One thousand and ten records were identified and 19 research articles met the inclusion criteria. These studies were heterogeneous in design and methodology, type of assessment and outcomes, so only descriptive analysis (narrative reporting) was possible. Results Prevalence of swallowing difficulties in patients with dementia ranged from 13 to 57%. Dysphagia developed during the late stages of frontotemporal dementia (FTD), but it was seen during the early stage of Alzheimer's dementia (AD). Limited evidence was available on the usefulness of diagnostic tests, effect of postural changes, modification of fluid and diet consistency, behavioral management and the possible use of medications. Use of Percutaneous Endoscopic Gastrostomy (PEG) tubes in advanced dementia, did not show benefit with regards to survival, improvement in QOL, or reduction in aspiration pneumonia. Significant gaps exist regarding the evidence for the evaluation and management of dysphagia in dementia.
Sarcopenia and frailty are commonly encountered in patients with end‐stage liver disease and are associated with adverse clinical outcomes, including decompensation and wait‐list mortality. The ...impact of these entities in patients with differing disease etiologies has not been elucidated. We aim to ascertain the change in their prevalence over time on the wait list and determine their impact on hospitalization, delisting, and wait‐list survival, specifically for patients with nonalcoholic steatohepatitis (NASH) and alcoholic liver disease (ALD). Adult patients who were evaluated for their first liver transplant from 2014 to 2016 with a primary diagnosis of NASH (n = 136) or ALD (n = 129) were included. Computed tomography scans were used to determine the presence of sarcopenia and myosteatosis. Frailty was diagnosed using the Rockwood frailty index. Patients with NASH had a significantly lower prevalence of sarcopenia (22% versus 47%; P < 0.001) but a significantly higher prevalence of frailty (49% versus 34%; P = 0.03) when compared with patients with ALD at the time of listing. In patients with NASH, sarcopenia was not associated with adverse events, but a higher frailty score was associated with an increased length of hospitalization (P = 0.05) and an increased risk of delisting (P = 0.02). In patients with ALD, univariate analysis showed the presence of sarcopenia was associated with an increased risk of delisting (P = 0.01). In conclusion, sarcopenia and frailty occur with differing prevalence with variable impact on outcomes in wait‐listed patients with NASH and ALD.
Background
Skeletal muscle is known to play a role in hepatic encephalopathy. Fatty infiltration of the muscle (myosteatosis) and muscle mass depletion (sarcopenia) are frequent complications of ...cirrhosis.
Purpose
The purposes of the study were to investigate if myosteatosis and sarcopenia are associated with overt hepatic encephalopathy in patients with cirrhosis and to evaluate their impact on mortality.
Methods
A total of 675 cirrhotic patients were studied. Computed tomography scans were used to analyze the skeletal muscle. Hepatic encephalopathy was defined by either a hepatic encephalopathy-related hospitalization and/or taking ammonia-lowering treatment (i.e., lactulose, rifaximin).
Results
Myosteatosis was observed in 348 patients (52%), sarcopenia in 242 (36%), and hepatic encephalopathy in 128 (19%) patients. Both myosteatosis (70 vs. 45%,
p
< 0.001) and sarcopenia (53 vs. 32%,
p
< 0.001) were more frequent in patients with hepatic encephalopathy. By multivariable regression analysis, both myosteatosis and sarcopenia were associated with a higher risk of hepatic encephalopathy, independent of the MELD score (OR 2.25; 95% CI, 1.32–3.85,
p
= 0.003 and OR 2.42; 95% CI, 1.43–4.10,
p
= 0.001, respectively). In univariate Cox proportional hazards analysis, sarcopenia (csHR 2.02; 95% CI, 1.57–2.58,
p
< 0.001), myosteatosis (csHR 1.45; 95% CI, 1.16–2.91,
p
= 0.004), and hepatic encephalopathy (csHR 1.61; 95% CI, 1.20–2.18,
p
= 0.002) were associated with mortality, but only sarcopenia was significant in the multivariable analysis (csHR 2.15; 95% CI, 1.52–3.05,
p
< 0.001).
Conclusions
Myosteatosis and sarcopenia are independently associated with overt hepatic encephalopathy in patients with cirrhosis. The association between hepatic encephalopathy and mortality may be explained at least partially by the presence of sarcopenia. These results identify the importance of muscle mass and suggest therapeutic strategies to attenuate muscle mass loss and improve muscle quality.
Liver transplantation (LT) is the definitive treatment for end‐stage liver disease. Unfortunately, women are disadvantaged at every stage of the LT process. We conducted a literature review to ...increase the understanding of this disparity. Hormonal differences, psychological factors, and Model for End‐Stage Liver Disease (MELD) score inequalities are some pretransplantation factors that contribute to this disparity. In the posttransplantation setting, women have differing risk than men in most major outcomes (perioperative complications, rejection, long‐term renal dysfunction, and malignancy) and assessing the two groups together is disadvantageous. Herein, we propose interventions including standardized criteria for LT referral, using an alternate MELD, education for support of women, and motivating women to seek living donors. Understanding sex‐based differences will allow us to improve access, tailor management, and improve overall outcomes for all patients, particularly women.
Physiologic reserve is an important prognostic indicator. Because of its complexity, no single test can measure an individual’s physiologic reserve. Frailty is the phenotypic expression of decreased ...reserve and portends poor prognosis. Both subjective and objective tools have been used to measure one or more components of physiologic reserve. Most of these tools appear to predict pretransplant mortality, but only some predict posttransplant survival. Incorporation of these measures of physiologic reserve in the clinical and research settings including prediction models are reviewed, and the applicability to patient‐related outcomes are discussed. Commonly used tools, in patients with cirrhosis, that have been associated with clinical outcomes were reviewed. The strength of subjective tools lies in low‐cost, wide availability, and quick assessments at the bedside. A disadvantage of these tools is the manipulative capacity, restricting their value in allocation processes. The strength of objective tests lies in objective measurements and the ability to measure change. The disadvantages include complexity, increased cost, and limited accessibility. Heterogeneity in the definitions and tools used has prevented further advancement or a clear role in transplant assessment. Consistent use of objective tools, including the 6‐minute walk test, gait speed, Liver Frailty Index, or Short Physical Performance Battery, are recommended in clinical and research settings.
Frailty and sarcopenia are common complications of cirrhosis. Frailty has been described as an increased susceptibility to stressors secondary to a cumulative decline in physiologic reserve; this ...decline occurs with aging or is a result of the disease process, across multiple organ systems. Sarcopenia, a key component of frailty, is defined as progressive and generalized loss of skeletal muscle mass and strength. The presence of either of these complications is associated with increased morbidity and mortality, as these are tightly linked to decompensation and increased complication rates. Recognition of these entities is critical. Studies have shown improvement in muscle strength and function lead to reduced mortality, suggesting both frailty and sarcopenia are modifiable risk factors. In this review we outline the prevalence of frailty and sarcopenia in cirrhosis and the impact on clinical outcomes such as decompensation, hospitalization, and mortality. Existing and potential novel therapeutic approaches for frailty and sarcopenia are also reviewed.
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.
PDF
