DOI: 10.1111/liv.13720. EDITORIALS. Insights on clinical relevance of sarcopenia in patients with cirrhosis and sepsis. Skeletal muscle wasting, accompanied ...
DOI: 10.1111/liv.13720
EDITORIALS
Insights on clinical relevance of sarcopenia in patients with cirrhosis and sepsis similar features of infection was observed in sarcopenic and non-
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sarcopenic patients. Frequency and clinical features associated with sepsis has been
Skeletal muscle wasting, accompanied by weakness and poor functional capacity, is a frequent finding in patients with cirrhosis. The term sarcopenia has been established to objectively describe this condition, characterized by progressive and generalized loss of skeletal muscle mass and strength, and has become a topic of prolific exploration in cirrhosis over the last few years. Currently, the evaluation of sarcopenia in patients with cirrhosis appears in over 1500 publications. Low muscle mass and impaired functional capacity of skeletal muscle associates with poor clinical outcomes in patients with cir1-3
rhosis.
Another significant point to declare regarding this feature
is that its association with adverse outcome is independent of the 4
severity of liver disease. Quantitative and reproducible techniques are required to diagnose and study this muscle loss, and these are represented in the literature predominantly by indirect techniques such as anthropometry, and bioelectrical impedance; and direct measurements like computed tomography (CT), and magnetic resonance imaging. The accuracy of indirect assessments such as anthropometry and bioelectrical impedance may be limited by the alterations in fat deposits in the elderly and the presence of fluid retention, which 5
is a frequent complication in patients with cirrhosis. Importantly, CT has been acknowledged as the gold standard for the recognition of low muscle mass by the European Working Group on Sarcopenia in Older People.
6
On the other hand, bacterial infections are a common complication of cirrhosis. Essentially, once infection develops, septic shock, acute renal failure, hepatic encephalopathy and multiorgan failure might follow, which adversely affect survival. In fact, in-hospital mortality of cirrhotic patients with infection is higher than 15%, and 7
infections are responsible for up to 50% of deaths in cirrhosis. 8
In this issue of Liver International, Lucidi et al, provided valuable insight into the relevance of sarcopenia and investigated the prognostic significance of low muscle mass in 74 hospitalized patients with cirrhosis and sepsis. Among anthropometric markers (low muscle mass, fat depletion and decreased muscle strength), only low muscle mass was associated with short-term mortality and the development of complications, such as hyponatremia, and hepatic encephalopathy. Sarcopenia presented in 43% of the patients and
explored in patients with cirrhosis; however, there is paucity in the knowledge related to the clinical implications of bacterial infections in sarcopenic patients with cirrhosis (Table 1). In a study by our group in 112 patients with cirrhosis, sarcopenic patients had a higher risk of sepsis-related mortality, but no significant difference in the risk of liver failure or liver cancer related mortality were found, when compared to non-sarcopenic patients. 2 To our knowledge, at present no other studies exist regarding the association between anthropometric measures and outcomes in patients with cirrhosis and episodes of sepsis, which is an interesting and appreciated contribution of this study. Of note, the study analysed the implications of sarcopenia in relation to the severity of cirrhosis, providing further insight into the issue that the negative effect of sarcopenia on in-hospital mortality was more prominent in patients with mild-to-moderate severity of liver disease (Child-Pugh A-B). Although this study outlines significant contributions to our advancing knowledge of sarcopenia in cirrhosis and its complications in patients with sepsis, some notes of caution are in order. The authors created multivariate Cox regression to find predictors of in-hospital mortality. However, some aspects of this analysis are questionable. It is not possible to judge from the presented Cox results, the reference group for liver disease severity. Whether Child-Pugh class A-B was chosen as the reference group or each class was considered as independent variable needs to be clarified. On the other hand, sarcopenia was an independent factor for short-term mortality, but there might be some interactions between sarcopenia and liver disease severity as no significant difference in in-hospital mortality was observed between sarcopenic and non-sarcopenic patients in Child- Pugh class C, demonstrating the superiority of liver disease severity to sarcopenia in predicting mortality. Moreover, other explanatory variables such as age and gender have not been taken into account in the multivariate model. It was also concluded that sarcopenia caused a negative impact on mortality, yet due to the retrospective nature of the study, this result implies the association, but not necessarily the causality. Also, there would be a greater scientific interest to show probability curves depicting short-term survival. Mid-arm-muscle-circumference (MAMC) is still being debated as a practical prognostic anthropometric measure.9 A previous study identified low muscle mass defined by mid-arm muscle circumference as an independent predictor of survival in hospitalized
Editorial for LIVint-17-01249.R1 “A low muscle mass increases mortality in compensated cirrhotic patients with sepsis” Lucidi et al.
cirrhotic patients.10 Lucidi et al, 8 used MAMC to assess muscle
786 | wileyonlinelibrary.com/journal/liv © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Liver International. 2018;38:786–788.
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EDITORIAL
TA B L E 1 Clinical studies describing an association between sarcopenia and sepsis in patients with cirrhosis Body composition assessment
Author/Year
Study population
Main finding
Merli et al (2010)18
150 patients with cirrhosis hospitalized to a tertiary-c are
Mid-arm muscle circumference
• Malnutrition was more common in patients with infection. • Protein malnutrition was independent predictors for infections and sepsis. • Sepsis (P = .005; 95% CI, 1.7-21.4) and protein malnutrition (P = .001; 95% CI, 2.8-38.5) increased mortality among patients in the hospital.
Merli et al (2010)19
38 consecutive patients awaiting LT
Mid-arm muscle circumference
• The proportion of the patients with bacterial infection after LT was significantly higher in malnourished patients with depleted muscle.
Montano-Loza et al (2012)2
112 patients with cirrhosis evaluated for LT
CT at the level of the third lumbar vertebrae
• Higher frequency of sepsis-related (22% vs 8%, P = .02) but not liver failure mortality was observed in sarcopenic compared to non-sarcopenic patients.
Masuda et al (2014)20
204 patients within a month before LT
CT-measured Psoas muscle
• Sarcopenia was a novel predictor of mortality and sepsis after LT. • Early enteral nutrition decreased the incidence of postoperative sepsis even in patients with sarcopenia.
CT, Computed tomography scan; LT, liver transplantation.
mass, which showed significant, but weak correlation with CT-
prognostic information to the model for end-s tage liver disease
determined skeletal muscle mass, in a previous work by the same
(MELD) score.
group of researchers11 and others.12 Novel assessments such as
Importantly, whether patients with cirrhosis and sarcopenia
thigh muscle thickness measured by bedside ultrasound strongly
might benefit from antibiotic prophylaxis, same as patients with pre-
associated with sarcopenia in patients with cirrhosis, 3 which might
vious episodes of spontaneous bacterial peritonitis, or patients with
be more appropriate than conventional anthropometrics for mea-
low protein levels in the ascitic fluid with either impaired renal func-
suring lean body mass.13 Actually, MAMC is calculated from mid-
tion, low serum sodium or liver failure,16,17 needs to be established
arm circumference and triceps skinfold thickness, and therefore,
in prospective clinical control trials.
some of the finding associated with low MAMC might be related to
In conclusion, current study by Lucidi et al, 8 emphasizes the
loss of subcutaneous adipose tissue, which has been shown to be
importance of muscularity assessment as part of nutritional
associated with mortality mainly in female patients with cirrhosis.14
screening, to better predict outcomes in patients with cirrhosis.
Last, prevalence of sarcopenia in cirrhosis has been reported to
However, prospective longitudinal studies with larger number of
be between 25% and 70%, with a higher frequency in male patients.15
patients are required to overcome the obstacles in our current
The prevalence of sarcopenia and its association with outcomes de-
understanding of the predictive value of sarcopenia in cirrhosis.
pends on how sarcopenia is defined. In this study, authors compared MAMC values to the fifth percentile of age and gender-matched normal population, derived from the United States National Health and Nutritional Examination Survey (NHANES). In another study, values
C O N FL I C T O F I N T E R E S T The authors do not have any disclosures to report.
of MAMC were compared with the tenth percentile of NHANES to define low muscle mass in patients with cirrhosis evaluated for liver transplantation.11 Generally, the choice of cutoff may be questioned as it has been driven from North American population representing
ORCID Aldo J. Montano-Loza
severe malnutrition in healthy populations. Additional studies are
Maryam Ebadi
needed to determine the utility of MAMC to detect sarcopenia, the ideal cutoff for sarcopenia as a determinant of functional impairment and survival in each gender; racial and ethnic differences also need to
Aldo J. Montano-Loza Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
be studied. Despite these limitations, the findings of this study are intriguing because they suggest that information of a practical and accessible anthropometric measurement can be used objectively, and the finding of sarcopenia by this method might identify cirrhotic individuals who are at high risk of death from sepsis. Sarcopenia, thus joins hyponatremia, hepatic encephalopathy and aetiology of liver disease as supplemental factors that might add short-term
http://orcid.org/0000-0002-2511-7980
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EDITORIAL
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