Regístrese
Buscar en
Annals of Hepatology
Toda la web
Inicio Annals of Hepatology Association between sarcopenia and hepatic encephalopathy: A systematic review a...
Journal Information
Share
Share
Download PDF
More article options
Visits
23
Concise reviews
DOI: 10.1016/j.aohep.2019.06.007
Open Access
Available online 16 August 2019
Association between sarcopenia and hepatic encephalopathy: A systematic review and meta-analysis
Visits
23
Karn Wijarnpreechaa,b, Monia Werlangb, Panadeekarn Panjawatananc, Paul T. Kronerb, Wisit Cheungpasitpornd, Frank J. Lukensb, Surakit Pungpapongb, Patompong Ungpraserte,
Corresponding author
p.ungprasert@gmail.com

Corresponding author at: 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand.
a Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA
b Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
c Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
d Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA
e Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
This item has received
23
Visits

Under a Creative Commons license
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (3)
Show moreShow less
Tables (1)
Table 1. Main characteristics of the studies included in this meta-analysis.
Additional material (2)
Abstract

Studies have suggested that the presence of sarcopenia in patients with cirrhosis could be a predisposing risk factor for hepatic encephalopathy. This systematic review and meta-analysis were conducted to summarize all available evidence on this relationship. A systematic review was carried out in Medline and EMBASE database through December 2018 to identify studies that recruited patients with cirrhosis from any causes and collected data on the presence of minimal or overt hepatic encephalopathy as well as sarcopenia. All study designs (case–control, cohort and cross-sectional studies) were eligible for the meta-analysis. Odds ratio (OR) and 95% confidence interval (CI) were extracted from the included studies and were pooled together using random-effect, generic inverse variance method of DerSimonian and Laird. Five cross-sectional studies with a total of 1,713 patients met our eligibility criteria and were included into the meta-analysis. We found a significantly higher risk of both mild and overt hepatic encephalopathy among cirrhotic patients with sarcopenia when compared with cirrhotic patients without sarcopenia with the pooled OR of 3.34 (95% CI: 1.68–6.67; I2=37%) and 2.05 (95% CI: 1.28–3.29; I2=61%), respectively. This systematic review and meta-analysis demonstrated a significant association between sarcopenia and hepatic encephalopathy among patients with cirrhosis.

Keywords:
Sarcopenia
Frailty
Hepatic encephalopathy
Meta-analysis
Full Text
1Introduction

Hepatic encephalopathy is one of the most important complications of chronic liver disease that is found in approximately 40% of cirrhotic patients [1]. It is caused by hyperammonemia which is a consequence of liver dysfunction and porto-systemic shunt [2]. The reported inpatient mortality rate of hepatic encephalopathy is as high as 15% [3]. Known precipitating factors for exacerbation of hepatic encephalopathy include infection, gastrointestinal bleeding, diuretic overdose, electrolyte imbalance and constipation [4,5].

Sarcopenia is a syndrome of decreased muscle mass, strength and function [6]. It is commonly seen in patients with chronic diseases, including liver cirrhosis [7–10]. Interestingly, the presence of sarcopenia may serve as a predisposing factor for hepatic encephalopathy among patients with cirrhosis as muscle is involved in ammonia disposal process by converting ammonia into glutamine, which is subsequently excreted by the kidneys [11–15]. Therefore, muscle wasting can contribute to impairment of ammonia detoxification, leading to hyperammonemia and hepatic encephalopathy [16]. In fact, significant association between sarcopenia and risk of hepatic encephalopathy has been observed by several clinical studies although the true magnitude of the risk remains unclear because the reported relative risk varied considerably across the studies, possibly due to difference in patient population and methods used to identify sarcopenia and hepatic encephalopathy [11–15]. This systematic review and meta-analysis were conducted with the aims to shed more light into this possible relationship by identifying all relevant studies and summarizing their results together.

2Methods2.1Information sources and search strategy

A systematic literature review of MEDLINE and EMBASE database was carried out by reviewing all indexed articles through December 2018 to identify all original studies that investigated the association between sarcopenia and hepatic encephalopathy. The systematic literature review was independently conducted by three investigators (K.W., P.P., and P.U.) using the search strategy that included the terms for “sarcopenia”, “frailty”, “muscle atrophy”, “hepatic encephalopathy” as described in online supplementary data 1. No language limitation was applied. A manual search for additional potentially applicable studies using references of selected included articles was also performed. This meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement which is provided as online supplementary data 2.

2.2Selection criteria

Studies that were eligible for this meta-analysis needed to recruit patients with cirrhosis from any causes and collected data on the presence of minimal or overt hepatic encephalopathy as well as sarcopenia. All study designs, including case–control, cross-sectional and cohort studies, were eligible for this meta-analysis. The association between hepatic encephalopathy and sarcopenia needed to be investigated and odds ratios (ORs) and 95% confidence intervals (CIs) or sufficient raw data to calculate those ratios were provided. Inclusion was not limited by study size. When more than one study utilizing the same database/cohort was available, the study with the most comprehensive data/analyses was included.

Retrieved articles were independently reviewed for their eligibility by the same three investigators (K.W., P.P., and P.U.). Disagreement was resolved by conference with all investigators. The modified Newcastle-Ottawa scale as described by Herzog et al. was used for quality assessment of the included studies [17]. The scale evaluated quality of cross-sectional study based on seven factors, including representativeness of sample, sample size, non-respondent rate, ascertain of the exposure, comparability of the two groups, assessment of the outcome and statistical test.

2.3Data abstraction

A structured information collection form was used to retrieve the following data from each study: title of the study, name of the first author, study design, year of publication, year of the study, country where the study was conducted, number of subjects, demographics of subjects, methods used to diagnose sarcopenia and hepatic encephalopathy (both overt and minimal hepatic encephalopathy), adjusted effect estimates with 95% CI and covariates that were adjusted in the multivariable analysis.

To ensure the accuracy, this data extraction process was independently performed by two investigators (K.W. and P.P.) and was reviewed by the senior investigator (P.U.).

2.4Statistical analysis

Data analysis was performed using the Review Manager 5.3 software from the Cochrane Collaboration (London, United Kingdom). Adjusted point estimates from each study were consolidated by the generic inverse variance method of DerSimonian and Laird, which assigned the weight of each study for the pooled analysis based on its variance (higher weight is given to study with lower variance) [18]. Random-effect model, rather than fixed-effect model, was used as the assumption of fixed-effect model that all studies, regardless of study design and background population, should give rise to the same result, is not true in almost all circumstances. Cochran's Q test and I2 statistic were used to determine the between-study heterogeneity. A value of I2 of 0–25% represents insignificant heterogeneity, 26–50% represents low heterogeneity, 51–75% represents moderate heterogeneity and more than 75% represents high heterogeneity [19]. If sufficient number of studies is identified, evaluation for publication bias will be performed using visualization of funnel plot.

3Results

A total of 6,085 potentially eligible articles were identified using our search strategy (2,295 articles from Medline and 3,790 articles from EMBASE). After exclusion of 1,913 duplicated articles, 4,172 articles underwent title and abstract review. Four-thousand and one hundred and forty-nine articles were excluded at this stage since they were case reports, case series, correspondences, review articles, in vitro studies, animal studies or interventional studies, leaving 23 articles for full-text review. Fourteen of them were excluded after the full-length review as they did not report the outcome of interest while three articles were excluded since they were descriptive studies without comparative analysis. A total of six cross-sectional studies [11–15] met the eligibility criteria. However, two studies [11,19] utilized the same database and only the study with more comprehensive data [19] was included into the meta-analysis to avoid double-counting of the same patients. Finally, five cross-sectional studies with 1,713 participants were included into the final analysis [11–15]. The literature review process is shown in Fig. 1. The characteristics and quality appraisal of the included studies are presented in Table 1. It should be noted that the inter-rater agreement for the quality assessment using the modified Newcastle-Ottawa scale was high with the kappa statistics of 0.72.

Fig. 1.

Literature review process.

(0.35MB).
Table 1.

Main characteristics of the studies included in this meta-analysis.

Study  Merli et al. [14]  Hanai et al. [13]  Nardelli et al. [15]  Bhanji et al. [11]  Engelmann et al. [12] 
Country  Italy  Japan  Italy  Canada  Germany 
Study design  Cross-sectional study  Cross-sectional study  Cross-sectional study  Cross-sectional study  Cross-sectional study 
Year  2013  2017  2017  2018  2018 
Sample size  248  120  46  675  624 
Participants  Consecutive cirrhotic patients hospitalized at Sapienza University of Rome Hospital, Italy, from June 2009 to December 2011 were prospectively recruited.All participants underwent neurocognitive and nutritional assessment.  Cirrhotic patients seen at Gifu University Hospital, Japan, between March 2013 and April 2016 were identified from medical record review. Only patients underwent tests for MHE and nutritional status were included.  Consecutive cirrhotic patients Sapienza seen at University of Rome Hospital, Italy, were prospectively recruited.All participants underwent CT scan of muscle and neurocognitive assessment.  Cirrhotic patients assessed for liver transplantation at the University of Alberta Hospital, Canada between January 2000 and May 2014 were identified from medical record review. Only patients who underwent CT scan for muscle assessment were included.  Cirrhotic patients aged 18 years and older assessed for liver transplantation at the University Hospital Leipzig, Germany between March 2001 and September 2014 were identified from medical record. Only patients who underwent CT scan for muscle assessment were included. 
Diagnosis of sarcopenia  Sarcopenia was diagnosed by measurement of MAMC (<5th percentile for general population matched age and sex)  Sarcopenia was diagnosed based on ASMI (<7.0kg/m2 in men and <5.7kg/m2 in women)  Sarcopenia was diagnosed based on sex-specific SMI cut-offs  Sarcopenia was diagnosed based on CT scan showing L3 skeletal muscle index of <50cm2/m2 in men and <39cm2/m2 in women  Sarcopenia was diagnosed based on PSMI (<22.38cm/m2 in men and <19.23cm/m2 in women) 
Diagnosis of HE  OHE was diagnosed clinically by applying the West Haven criteriaMHE were diagnosed by PHES (score <−4)  MHE was diagnosed using NP-test system (abnormal test results >2/4 subtests)  MHE was diagnosed using PHES test (score ≤−4)  Diagnosis of OHE was based on medical record of history of admission for confusion/disorientation attributed to HE and/or treated with lactulose/rifaximin  Diagnosis of OHE was based on review of medical records. 
Confounder adjusted in multivariate analysis  N/A  Presence of esophageal varices, Child-Pugh score, INR, ammonia level, BCAA level and BCAA supplementation  N/A  Alcohol cirrhosis, MELD score, ascites and serum sodium  N/A 
Quality assessment (Newcastle-Ottawa scale)a  Selection: 4Comparability: 1Outcome: 3  Selection: 3Comparability: 2Outcome: 3  Selection: 4Comparability: 1Outcome: 3  Selection: 3Comparability: 2Outcome: 3  Selection: 3Comparability: 1Outcome: 3 

Abbreviations: MHE: minimal hepatic encephalopathy; OHE: overt hepatic encephalopathy; HE: hepatic encephalopathy; MAMC: mid-arm-muscle-circumference; HGS: handgrip strength; PHES: Psychometric Hepatic Encephalopathy Score; CT: computed tomography; MELD: Model for End-Stage Liver Disease; ASMI: appendicular skeletal muscle mass index; NP-test: neuropsychiatric test; INR: international normalized ratio; BCAA: branched chain amino acids; SMI: skeletal muscle index; PSMI: paraspinal muscle index.

a

Selection includes representativeness of sample, sample size, non-respondent rate and ascertain of the exposure; comparability includes control of confounders; outcome includes assessment of the outcome and statistical test.

3.1Association between sarcopenia and minimal hepatic encephalopathy

We found a significantly increased risk of minimal hepatic encephalopathy among patients with sarcopenia with the pooled OR of 3.34 (95% CI, 1.68–6.67), as demonstrated in Fig. 2. The between-study heterogeneity was low with an I2 of 37%.

Fig. 2.

Forest plot of the association between sarcopenia and minimal hepatic encephalopathy.

(0.13MB).
3.2Association between sarcopenia and overt hepatic encephalopathy

We found a significantly increased risk of overt hepatic encephalopathy among patients with sarcopenia with the pooled OR of 2.05 (95% CI, 1.28–3.29), as demonstrated in Fig. 3. The between-study heterogeneity was moderate with an I2 of 61%.

Fig. 3.

Forest plot of the association between sarcopenia and overt hepatic encephalopathy.

(0.16MB).
3.3Evaluation for publication bias

Evaluation for publication bias using funnel plot could not be performed due to the limited number of the included studies.

4Discussion

Sarcopenia is common among patients with cirrhosis because of several contributing factors. The major factor is malnutrition as a result of physiological and anatomical changes associated with end stage liver disease such as ascites causing early satiety, elevated inflammatory cytokines affecting appetite, abnormal gut motility and poor nutrient absorption due to portal hypertension [20–22]. Patients with cirrhosis are also in hypermetabolic state and have a decreased capacity of glucoeneogenesis, which would lead to muscle breakdown to mobilize energy and muscle amino acids [23]. In addition, some specific etiologies of chronic liver disease are associated with the increased risk of sarcopenia. For instance; alcoholic cirrhosis, especially when associated with active alcoholism and poverty, can lead to poor diet and macro- and micronutrients deficiencies [21]; chronic viral hepatitis can lead to a state of chronic inflammation, resulting in decreased appetite [21,23]; elevated insulin resistance in NAFLD could impair the uptake of glucose and subsequently trigger gluconeogenesis via muscle breakdown [20].

The current systematic review and meta-analysis found that the presence of sarcopenia in patients with cirrhosis is associated with an approximately two-fold and three-fold increased risk of overt and minimal hepatic encephalopathy, respectively. This observation suggests that the presence of sarcopenia may adversely affect the outcome of cirrhosis. The most plausible explanation for this increased risk lies in the metabolic function of skeletal muscle as it can convert ammonia into glutamine, which can then be excreted by the kidneys [24]. This is an important alternative pathway for ammonia homeostasis when liver function is impaired. In sarcopenic patients, because of the lack of muscle mass, this compensatory mechanism is decreased or absent and, thus, increase the risk of hyperammonemia and hepatic encephalopathy [25].

Nonetheless, due to the cross-sectional nature of the primary studies, it is also possible that the observed association may have a reverse cause-and-effect direction. It is possible that hyperammonemia, the main underlying etiology of hepatic encephalopathy, could predispose cirrhotic patients to sarcopenia by promoting muscle autophagy and reducing muscle protein synthesis [26–28]. In fact, a study in patients with cirrhosis has demonstrated that once hyperammonemia was reversed, a significant recovery in the rate of protein synthesis was observed [29].

Although the quality of the included studies was high as reflected by the high modified Newcastle-Ottawa scores and the literature review process was thorough, we acknowledge that this study has some limitations and the results should be interpreted with caution. First, we could not assess for the presence of publication bias due to the limited number of the included studies. Therefore, publication bias in favor of studies with positive association may have been presented. Second, as discussed earlier, all of the included studies were cross-sectional in nature, leaving the uncertainty in the direction of the cause-and-effect. Last, between-study heterogeneity was not low in the meta-analysis of overt hepatic encephalopathy which may jeopardize the validity of the pooled result. The difference in patient population (some studies included all cirrhotic patients whereas some studies included only cirrhotic patients evaluated for liver transplantation) and methods used to identify sarcopenia and hepatic encephalopathy were probably responsible for this variation in effect size. Unfortunately, further analysis, such as subgroup analysis and meta-regression, to explore this between-study heterogeneity could not be performed due to the limited number of included studies.

In summary, this study demonstrated a significant association between hepatic encephalopathy and sarcopenia among patients with cirrhosis. Further investigations are still required to determine whether this association is causal and the role of management of sarcopenia among patients with cirrhosis in clinical practice.AbbreviationsOR

odds ratio

CI

confidence interval

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

NAFLD

non-alcoholic fatty liver disease

Authors’ contributions

All authors had access to the data and a role in writing the manuscript.

Wijarnpreecha K, acquisition of data, analysis and interpretation of data, drafting the articles, final approval; Werlang M, acquisition of data, drafting the articles, final approval; Panjawatanan P, acquisition data, interpretation the data, final approval; Kroner PT, interpretation the data, revising the article, final approval; Cheungpasitporn W, acquisition of data, interpretation of data, final approval; Lukens FJ, Pungpapong S, interpretation the data, revising the article, final approval; Ungprasert P, conception and design of the study, critical revision, final approval.

Funding

None declared.

Conflict of interest

We do not have any financial or non-financial potential conflicts of interest.

Appendix A
Supplementary data

The following are the supplementary data to this article:

References
[1]
P. Amodio, F. Del Piccolo, E. Petteno, D. Mapelli, P. Angeli, R. Iemmolo, M. Muraca, et al.
Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients.
J Hepatol, 35 (2001), pp. 37-45
[2]
A. Hadjihambi, N. Arias, M. Sheikh, R. Jalan.
Hepatic encephalopathy: a critical current review.
Hepatol Int, 12 (2018), pp. 135-147
[3]
M. Stepanova, A. Mishra, C. Venkatesan, Z.M. Younossi.
In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009.
Clin Gastroenterol Hepatol, 10 (2012), pp. 1034-1410
[4]
H. Vilstrup, P. Amodio, J. Bajaj, J. Cordoba, P. Ferenci, K.D. Mullen, K. Weissenborn, et al.
Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.
Hepatology, 60 (2014), pp. 715-735
[5]
W. Bleibel, A.M. Al-Osaimi.
Hepatic encephalopathy.
Saudi J Gastroenterol, 18 (2012), pp. 301-309
[6]
E. Marty, Y. Liu, A. Samuel, O. Or, J. Lane.
A review of sarcopenia: enhancing awareness of an increasingly prevalent disease.
[7]
V.A. Souza, D. Oliveira, S.R. Barbosa, J. Correa, F.A.B. Colugnati, H.N. Mansur, N. Fernandes, et al.
Sarcopenia in patients with chronic kidney disease not yet on dialysis: analysis of the prevalence and associated factors.
PLOS ONE, 12 (2017), pp. e0176230
[8]
H. Trierweiler, G. Kisielewicz, T. Hoffmann Jonasson, R. Rasmussen Petterle, C. Aguiar Moreira, V. Zeghbi Cochenski Borba.
Sarcopenia: a chronic complication of type 2 diabetes mellitus.
Diabetol Metab Syndr, 10 (2018), pp. 25
[9]
G. Kim, S.H. Kang.
Prognostic value of sarcopenia in patients with liver cirrhosis: a systematic review and meta-analysis.
PLOS ONE, 12 (2017), pp. e0186990
[10]
C.I. Li, T.C. Li, W.Y. Lin, C.S. Liu, C.C. Hsu, C.A. Hsiung, C.Y. Chen, et al.
Combined association of chronic disease and low skeletal muscle mass with physical performance in older adults in the Sarcopenia and Translational Aging Research in Taiwan (START) study.
BMC Geriatr, 15 (2015), pp. 11
[11]
R.A. Bhanji, C. Moctezuma-Velazquez, A. Duarte-Rojo, M. Ebadi, S. Ghosh, C. Rose, A.J. Montano-Loza.
Myosteatosis and sarcopenia are associated with hepatic encephalopathy in patients with cirrhosis.
[12]
C. Engelmann, S. Schob, I. Nonnenmacher, L. Werlich, N. Aehling, S. Ullrich, T. Kaiser, et al.
Loss of paraspinal muscle mass is a gender-specific consequence of cirrhosis that predicts complications and death.
Aliment Pharmacol Ther, 48 (2018), pp. 1271-1281
[13]
T. Hanai, M. Shiraki, S. Watanabe, T. Kochi, K. Imai, A. Suetsugu, K. Takai, et al.
Sarcopenia predicts minimal hepatic encephalopathy in patients with liver cirrhosis.
[14]
M. Merli, M. Giusto, C. Lucidi, V. Giannelli, I. Pentassuglio, V. Di Gregorio, B. Lattanzi, et al.
Muscle depletion increases the risk of overt and minimal hepatic encephalopathy: results of a prospective study.
Metab Brain Dis, 28 (2013), pp. 281-284
[15]
S. Nardelli, B. Lattanzi, S. Torrisi, F. Greco, A. Farcomeni, S. Gioia, M. Merli, et al.
Sarcopenia is risk factor for development of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt placement.
Clin Gastroenterol Hepatol, 15 (2017), pp. 934-936
[16]
B. Lattanzi, D. D’Ambrosio, M. Merli.
Hepatic encephalopathy and sarcopenia: two faces of the same metabolic alteration.
J Clin Exp Hepatol, 9 (2019), pp. 125-130
[17]
R. Herzog, M.J. Alvarez-Pasquin, C. Diaz, J.L. Del Barrio, J.M. Estrada, A. Gil.
Are healthcare workers’ intentions to vaccinate related to their knowledge, beliefs and attitudes? A systematic review.
BMC Public Health, 13 (2013), pp. 154
[18]
R. DerSimonian, N. Laird.
Meta-analysis in clinical trials.
Control Clin Trials, 7 (1986), pp. 177-188
[19]
J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman.
Measuring inconsistency in meta-analyses.
[20]
K. Cheung, S.S. Lee, M. Raman.
Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies.
Clin Gastroenterol Hepatol, 10 (2012), pp. 117-125
[21]
E.T. Tsiaousi, A.I. Hatzitolios, S.K. Trygonis, C.G. Savopoulos.
Malnutrition in end stage liver disease: recommendations and nutritional support.
J Gastroenterol Hepatol, 23 (2008), pp. 527-533
[22]
J. Dasarathy, N. Alkhouri, S. Dasarathy.
Changes in body composition after transjugular intrahepatic portosystemic stent in cirrhosis: a critical review of literature.
Liver Int, 31 (2011), pp. 1250-1258
[23]
T. Kachaamy, J.S. Bajaj, D.M. Heuman.
Muscle and mortality in cirrhosis.
Clin Gastroenterol Hepatol, 10 (2012), pp. 100-102
[24]
C. Lucero, E.C. Verna.
The role of sarcopenia and frailty in hepatic encephalopathy management.
Clin Liver Dis, 19 (2015), pp. 507-528
[25]
S.W. Olde Damink, R. Jalan, D.N. Redhead, P.C. Hayes, N.E. Deutz, P.B. Soeters.
Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS.
Hepatology, 36 (2002), pp. 1163-1171
[26]
G. Marino, G. Kroemer.
Ammonia: a diffusible factor released by proliferating cells that induces autophagy.
Sci Signal, 3 (2010), pp. pe19
[27]
J. Qiu, C. Tsien, S. Thapalaya, A. Narayanan, C.C. Weihl, J.K. Ching, B. Eghtesad, et al.
Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis.
Am J Physiol Endocrinol Metab, 303 (2012), pp. E983-E993
[28]
J. Qiu, S. Thapaliya, A. Runkana, Y. Yang, C. Tsien, M.L. Mohan, A. Narayanan, et al.
Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-kappaB-mediated mechanism.
Proc Natl Acad Sci U S A, 110 (2013), pp. 18162-18167
[29]
A. Kumar, G. Davuluri, R.N.E. Silva, M. Engelen, G.A.M. Ten Have, R. Prayson, N.E.P. Deutz, et al.
Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis.
Hepatology, 65 (2017), pp. 2045-2058
Copyright © 2019. Fundación Clínica Médica Sur, A.C.
Article options
Tools
Supplemental materials
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.