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Muscle loss and cirrhosis

Kamyar Kalantar-Zadeh, Connie M Rhee, Jason Chou, S Foad Ahmadi, Jongha Park, Joline Lt Chen, Alpesh N Amin
Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in the elderly...
March 2017: KI Reports
Rahima A Bhanji, Elizabeth J Carey, Liu Yang, Kymberly D Watt
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 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...
April 8, 2017: Clinical Gastroenterology and Hepatology
Jayshil J Patel, Craig J McClain, Menaka Sarav, Jill Hamilton-Reeves, Ryan T Hurt
Diseases leading to critical illness induce proteolysis resulting in muscle wasting and negative nitrogen balance. Muscle wasting has been associated with poor intensive care unit (ICU)-related outcomes, including an increased risk for mortality. Acute kidney injury (AKI) represents a common organ dysfunction associated with ICU-related disorders, such as sepsis, trauma, and respiratory failure. AKI and renal replacement therapy lead to amino acid loss. Decompensated liver cirrhosis (DLC) and acute liver failure (ALF) represent more severe forms of liver dysfunction leading to ICU admission...
April 2017: Nutrition in Clinical Practice
Cristina R Bosoi, Mariana M Oliveira, Rafael Ochoa-Sanchez, Mélanie Tremblay, Gabriella A Ten Have, Nicolaas E Deutz, Christopher F Rose, Chantal Bemeur
Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepatic encephalopathy. However, the effects of ammonia are not brain-specific and therefore may also affect other organs and tissues including muscle. The precise pathophysiological mechanisms underlying muscle wasting in chronic liver disease remains to be elucidated...
April 2017: Metabolic Brain Disease
Lindsey L Kennedy, Fanyin Meng, Julie K Venter, Tianhao Zhou, Walker A Karstens, Laura A Hargrove, Nan Wu, Konstantina Kyritsi, John Greene, Pietro Invernizzi, Francesca Bernuzzi, Shannon S Glaser, Heather L Francis, Gianfranco Alpini
Cholestasis is a condition that leads to chronic hepatobiliary inflammation, fibrosis, and eventually cirrhosis. Many microRNAs (miRs) are known to have a role in fibrosis progression; however, the role of miR-21 during cholestasis remains unknown. Therefore, the aim of this study was to elucidate the role of miR-21 during cholestasis-induced biliary hyperplasia and hepatic fibrosis. Wild-type (WT) and miR-21(-/-) mice underwent Sham or bile duct ligation (BDL) for 1 week, before evaluating liver histology, biliary proliferation, hepatic stellate cell (HSC) activation, fibrotic response, and small mothers against decapentaplegic 7 (Smad-7) expression...
December 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Jun Yang, Ya-Li Yu, Yu Jin, Ying Zhang, Chang-Qing Zheng
AIM: To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS: A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type)...
September 7, 2016: World Journal of Gastroenterology: WJG
Nirmala Mavila, Andrew Trecartin, Ryan Spurrier, Yi Xiao, Xiaogang Hou, David James, Xiaowei Fu, Brian Truong, Clara Wang, Gerald S Lipshutz, Kasper S Wang, Tracy C Grikscheit
: Liver disease affects large numbers of patients, yet there are limited treatments available to replace absent or ineffective cellular function of this crucial organ. Donor scarcity and the necessity for immunosuppression limit one effective therapy, orthotopic liver transplantation. But in some conditions such as inborn errors of metabolism or transient states of liver insufficiency, patients may be salvaged by providing partial quantities of functional liver tissue. After transplanting multicellular liver organoid units composed of a heterogeneous cellular population that includes adult stem and progenitor cells, both mouse and human tissue-engineered liver (TELi) form in vivo...
August 30, 2016: Stem Cells Translational Medicine
Rachel A Stern, Srinivasan Dasarathy, Paul E Mozdziak
Increased myostatin expression, resulting in muscle loss, has been associated with hyperammonemia in mammalian models of cirrhosis. However, there is evidence that hyperammonemia in avian embryos results in a reduction of myostatin expression, suggesting a proliferative myogenic environment. The present in vitro study examines species differences in myotube and liver cell response to ammonia using avian and murine-derived cells. Primary myoblasts and liver cells were isolated from embryonic day 15 and 17 chick embryos to be compared with mouse myoblasts (C2C12) and liver (AML12) cells...
February 2017: In Vitro Cellular & Developmental Biology. Animal
Srinivasan Dasarathy, Manuela Merli
Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments...
December 2016: Journal of Hepatology
Aldo J Montano-Loza, Paul Angulo, Judith Meza-Junco, Carla M M Prado, Michael B Sawyer, Crystal Beaumont, Nina Esfandiari, Mang Ma, Vickie E Baracos
BACKGROUND AND AIMS: Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients...
May 2016: Journal of Cachexia, Sarcopenia and Muscle
Anders Rasmussen Rinnov, Peter Plomgaard, Bente Klarlund Pedersen, Lise Lotte Gluud
CONTEXT: Follistatin is a liver-derived inhibitor of the muscle-growth inhibitor myostatin. Reduction in acute follistatin release may help explain muscle loss in liver cirrhosis. OBJECTIVE: The study aimed to investigate the capacity of acute follistatin release in patients with liver cirrhosis compared to healthy control participants. DESIGN, SETTING, AND PARTICIPANTS: To experimentally increase the glucagon-insulin ratio (mimicking the hormonal effect of exercise), we infused glucagon/somatostatin (to inhibit insulin secretion) and compared the acute follistatin increase in eight male cirrhosis patients with eight healthy control participants...
September 2016: Journal of Clinical Endocrinology and Metabolism
Dean P Larner, Stuart A Morgan, Laura L Gathercole, Craig L Doig, Phil Guest, Christopher Weston, Jon Hazeldine, Jeremy W Tomlinson, Paul M Stewart, Gareth G Lavery
Nonalcoholic fatty liver disease (NAFLD) defines a spectrum of conditions from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis and is regarded as the hepatic manifestation of the metabolic syndrome. Glucocorticoids can promote steatosis by stimulating lipolysis within adipose tissue, free fatty acid delivery to liver and hepatic de novo lipogenesis. Glucocorticoids can be reactivated in liver through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme activity. Inhibition of 11β-HSD1 has been suggested as a potential treatment for NAFLD...
September 2016: Endocrinology
Gangarao Davuluri, Dawid Krokowski, Bo-Jhih Guan, Avinash Kumar, Samjhana Thapaliya, Dharmvir Singh, Maria Hatzoglou, Srinivasan Dasarathy
BACKGROUND & AIMS: Increased skeletal muscle ammonia uptake with loss of muscle mass adversely affects clinical outcomes in cirrhosis. Hyperammonemia causes reduced protein synthesis and sarcopenia but the cellular responses to impaired proteostasis and molecular mechanism of l-leucine induced adaptation to ammonia induced stress were determined. METHODS: Response to activation of amino acid deficiency sensor, GCN2, in the skeletal muscle from cirrhotic patients and the portacaval anastomosis (PCA) rat were quantified...
November 2016: Journal of Hepatology
Atsushi Hiraoka, Kojiro Michitaka, Hidetaro Ueki, Miho Kaneto, Toshihiko Aibiki, Tomonari Okudaira, Takamasa Kawakami, Hiroka Yamago, Yoshifumi Suga, Hideomi Tomida, Yuji Miyamoto, Nobuaki Azemoto, Kenichiro Mori, Hideki Miyata, Eiji Tsubouchi, Tomoyuki Ninomiya, Masashi Hirooka, Masanori Abe, Bunzo Matsuura, Yoichi Hiasa
BACKGROUND/AIM: The frequency of sarcopenia, defined as loss of both muscle volume and strength, was analyzed in chronic liver disease (CLD). METHODS AND MATERIALS: From April to September 2015, 807 Japanese CLD patients treated as outpatients were enrolled (67.1±10.0 years, men : women=466 : 341, hepatitis C virus : hepatitis B virus : hepatitis B and C virus : alcohol : other=511 : 134 : 3 : 45 : 114). Sarcopenia was diagnosed when the patient showed muscle volume loss and reduced handgrip strength, whereas those with only muscle volume loss were classified as 'v-presarcopenia' and those with only reduced handgrip strength were classified as 's-presarcopenia'...
August 2016: European Journal of Gastroenterology & Hepatology
Seyed Soheil Saeedi Saravi, Mahmoud Ghazi-Khansari, Shahram Ejtemaei Mehr, Maliheh Nobakht, Seyyedeh Elaheh Mousavi, Ahmad Reza Dehpour
AIM: To explore the role of mammalian target of rapamycin (mTOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition. METHODS: Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon (CCl4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin (2 mg/kg per day). The QTc intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles were isolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system...
May 21, 2016: World Journal of Gastroenterology: WJG
Puneeta Tandon, Gavin Low, Marina Mourtzakis, Laura Zenith, Robert P Myers, Juan G Abraldes, Abdel Aziz M Shaheen, Hina Qamar, Nadia Mansoor, Michelle Carbonneau, Kathleen Ismond, Sumeer Mann, Alshimaa Alaboudy, Mang Ma
BACKGROUND & AIMS: The severe depletion of muscle mass at the third lumbar vertebral level (sarcopenia) is a marker of malnutrition and is independently associated with mortality in patients with cirrhosis. Instead of monitoring sarcopenia by cross-sectional imaging, we investigated whether ultrasound-based measurements of peripheral muscle mass, measures of muscle function, along with nutritional factors, are associated with severe loss of muscle mass. METHODS: We performed a prospective study of 159 outpatients with cirrhosis (56% male; mean age, 58 ± 10 years; mean model for end-stage liver disease score, 10 ± 3; 60% Child-Pugh class A) evaluated at the Cirrhosis Care Clinic at the University of Alberta Hospital from March 2011 through September 2012...
October 2016: Clinical Gastroenterology and Hepatology
L Augusti, L C Franzoni, L A A Santos, T B Lima, M V Ietsugu, K H Koga, S M Moriguchi, L E Betting, C A Caramori, G F Silva, F G Romeiro
Hepatic encephalopathy (HE) is a late complication of liver cirrhosis and is clearly associated with poor outcomes. Chronic liver insufficiency leads to progressive muscle wasting, impairing ammonia metabolism and thus increasing the risk for HE. Given the association between lean mass and adductor pollicis muscle thickness (APMT), it has been used to predict outcome and complications in many conditions, but not yet in cirrhotic patients. Therefore, this article aimed to study the association between HE manifestations and measures related to muscle mass and strength...
August 2016: Metabolic Brain Disease
Ragesh B Thandassery, Aldo J Montano-Loza
Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, malnutrition and muscle wasting (sarcopenia) constitute common complications which negatively impact survival, quality of life, and response to stressors, such as infection and surgery in patients with cirrhosis. Despite the important role that malnutrition and sarcopenia play in the prognosis of patients with cirrhosis, they are frequently overlooked, in part because nutritional assessment can be a difficult task in patients with cirrhosis due to fluid retention and/or overweight...
June 2016: Current Treatment Options in Gastroenterology
Srinivasan Dasarathy
PURPOSE OF REVIEW: Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and occurs in the majority of patients with liver disease. Lower muscle contractile function also contributes to the adverse consequences of sarcopenia. There are no effective therapies to prevent or reverse sarcopenia in liver disease. This review will discuss the advances in diagnosis, pathogenesis, and treatment options for sarcopenia in liver disease. RECENT FINDINGS: Sarcopenia increases mortality and risk of development of other complications of cirrhosis, and worsens postliver transplant outcomes while quality of life is decreased...
May 2016: Current Opinion in Gastroenterology
M Sinclair, P J Gow, M Grossmann, P W Angus
BACKGROUND: Sarcopenia (loss of muscle mass) is common in cirrhosis and is associated with poor outcomes. Current teaching recommends the use of protein supplementation and exercise, however, this fails to address many other factors which contribute to muscle loss in this setting. AIMS: To summarise existing knowledge regarding the aetiology of sarcopenia in cirrhosis, diagnostic modalities and the clinical significance of this condition. In addition to discuss recent research findings that may allow the development of more effective treatments...
April 2016: Alimentary Pharmacology & Therapeutics
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