Consilience in sarcopenia of cirrhosis

Abstract

Cirrhosis is the consequence of progression of many forms of necro-inflammatory disorders of the liver with hepatic fibrosis, hepatocellular dysfunction, and vascular remodeling. Reversing the primary hepatic disorder, liver transplantation, and controlling the complications are the major management goals. Since the former options are not available to the majority of cirrhotics, treating complications remains the mainstay of therapy. Sarcopenia and/or cachexia is the most common complication and adversely affects survival, quality of life, development of other complications of cirrhosis, and outcome after liver transplantation. With the increase in number of cirrhotic patients with hepatitis C and nonalcoholic fatty liver disease, the number of patients waiting for a liver transplantation is likely to continue to increase above the currently estimated 72.3/100,000 population. One of the critical clinical questions is to determine if we can treat sarcopenia of cirrhosis without transplantation. No effective therapies exist to treat sarcopenia because the mechanism(s) of sarcopenia in cirrhosis is as yet unknown. The reasons for this include the predominantly descriptive studies to date and the advances in our understanding of skeletal muscle biology and molecular regulation of atrophy and hypertrophy not being translated into the clinical practice of hepatology. Satellite cell biology, muscle autophagy and apoptosis, and molecular signaling abnormalities in the skeletal muscle of cirrhotics are also not known. Aging of the cirrhotic and transplanted population, use of mTOR inhibitors, and the lack of definitive outcome measures to define sarcopenia and cachexia in this population add to the difficulty in increasing our understanding of hepatic sarcopenia/cachexia and developing treatment options. Recent data on the role of myostatin, AMP kinase, impaired mTOR signaling resulting in anabolic resistance in animal models, and the rapidly developing field of nutriceuticals as signaling molecules need to be evaluated in human cirrhotics. Finally, the benefits of exercise reported in other disease states with sarcopenia may not be safe in cirrhotics due to the risk of gastrointestinal variceal bleeding due to an increase in portal pressure. This article focuses on the problems facing both muscle biologists and hepatologists in developing a comprehensive approach to sarcopenia in cirrhosis.

Effect of pretreatment psoas muscle mass on survival for patients with unresectable pancreatic cancer undergoing systemic chemotherapy

“…In general, skeletal muscle mass is regulated depending on the balance between protein synthesis and protein catabolism (12). Sarcopenia, defined as decreased skeletal muscle mass (DSMM) and muscle strength, has become a relevant clinical feature for understanding the effects of aging on clinical outcomes (13).…”

“…Sarcopenia is a commonly observed disorder in aged populations and is associated with disability, functional decline and frailty (13,14). Age-associated sarcopenia is defined as primary sarcopenia, whilst advanced malignancies, as well as chronic inflammatory diseases including renal, heart and liver diseases, can be the causes of secondary sarcopenia (12)(13)(14)(15)(16). Severe underlying diseases can lead to sarcopenia and cachexia, which involves body weight loss and muscle wasting.…”

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

“…Sarcopenia is a commonly observed disorder in aged populations and is associated with disability, functional decline and frailty (19,20). Generally, skeletal muscle mass is regulated depending on the balance between protein synthesis and protein breakdown (21). Patients with HCC often have underlying liver cirrhosis (LC), and skeletal muscle loss is a major characteristic of protein energy malnutrition in patients with LC (22,23).…”

“…Age-associated sarcopenia is defined as primary sarcopenia, whereas LC is one of the causes of secondary sarcopenia (19,22,23). Although commonly observed, malnutrition is frequently underdiagnosed or overlooked, and it is poorly characterized in patients with HCC and LC complications (21)(22)(23). In addition, to the best of our knowledge, although sarcopenia has been reported to be an adverse predictor in patients with HCC who may have a potential for curative therapy such as surgical resection, as well as in patients with several malignancies other than HCC, there have been no studies regarding the impact of sarcopenia on clinical outcomes in patients with HCC undergoing sorafenib therapy (18,(24)(25)(26)(27).…”

Protein Recommendations for Older Adults with Cirrhosis: A Review

“…It has been shown that 7.2-8.6% of older adult women consume protein levels below 0.66 g/kg/d and approximately 10-25% of older adults consume less than the recommended dietary allowance of protein of 0.8 g/kg/d [31] . After the age of 50 there is a 1% loss of muscle mass per year [9] . In addition, decreased physical activity and bed rest associated with hospitalization are very common in older adulthood and cirrhosis and contribute to loss of muscle mass [32] .…”