The optimal imaging diagnostic method of sarcopenia in liver transplantation: an unresolved issue

Liver cirrhosis is the end stage of multiple liver diseases with a high morbidity and mortality. Complications related to cirrhosis, including variceal bleeding, ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy, have been widely recognized (1-3). However, malnutrition, another common complication, has not been fully recognized in clinical practice. Indeed, classical prognostic models, such as Child-Turcotte-Pugh and model for end-stage liver disease (MELD), are lacking an objective assessment of malnutrition in cirrhotic patients (4-6).

Depletion in skeletal muscle mass, also known as sarcopenia, is a feature of malnutrition (7). Sarcopenia is a prognostic factor independently of the MELD score in patients waiting for liver transplantation (8). Recently, a meta-analysis by van Vugt et al. (9) showed that sarcopenia was associated with increased mortality on the liver transplantation waiting list (pooled hazard ratio =1.72, P=0.05) and after liver transplantation (pooled hazard ratio =1.84, P=0.02). Studies also found that sarcopenia impaired the quality of life, increased the incidence of complications, and worsened the outcome following liver transplantation (10).

Until now, several different imaging tools, such as computed tomography (CT), magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DEXA), ultrasonography (US), and approaches for measuring sarcopenia have been developed for evaluating skeletal muscle mass in patients waiting for liver transplantation. In this present editorial for the special issue, we briefly reviewed the findings of studies using different imaging tools and approaches.

CT

Total psoas muscle area (TPMA)

Englesbe et al. (11) measured the TPMA at the level of the fourth lumbar vertebrae (L4). A total of 163 liver transplant recipients were included. Cox regression analysis showed that TPMA was significantly associated with post-transplantation mortality (when TPMA decreased 1,000 mm², hazard ratio =3.7, P<0.0001). Masuda et al. (12) measured the TPMA at the level of the third lumbar vertebrae (L3). A total of 204 liver transplant recipients were included. The diagnostic criteria for sarcopenia were defined: TPMA <800 cm² in male and <380 cm² in female. Multivariate analysis showed that only sarcopenia was an independent prognostic factor (hazard ratio =2.06, P=0.047).

Skeletal muscle index (SMI)

Montano-Loza et al. (13) measured skeletal muscle area (SMA) at the L4 level. Skeletal muscle index (SMI) was calculated using the formula: SMI = SMA/height². A total of 112 cirrhotic patients were included. The diagnostic criteria for sarcopenia were defined: SMI <52.4 cm²/m² in male and <38.5 cm²/m² in female. The results showed that sarcopenia was significantly associated with higher mortality (hazard ratio =2.11, P=0.02). Similarly, Tandon et al. (14) also measured SMA at the same level and calculated SMI in 142 liver transplant recipients. The diagnostic criteria for sarcopenia were the same as that by Montano-Loza et al. The results also showed that sarcopenia was a significant risk factor for mortality (hazard ratio =2.36, P=0.009).

Transversal psoas muscle thickness (TPMT)

Durand et al. (8) used the TPMT/height for evaluating sarcopenia in 562 patients waiting for liver transplantation. The results showed that TPMT/height might be a prognostic factor for waiting list mortality independently of MELD score.

MRI

In the study by Praktiknjo et al. (15), fat-free muscle area (FFMA) was measured by MRI and TPMT was measured by CT in 116 patients who had undergone transjugular intrahepatic portosystemic shunt (TIPS) placement. The results showed that patients with sarcopenia diagnosed by FFMA had a significantly worse 3-year survival. FFMA was significantly increased after TIPS procedure.

DEXA

In a study by Belarmino et al. (16), appendicular skeletal muscle mass (ASM) was measured by using DEXA in 144 male cirrhotic patients. Appendicular skeletal muscle index (ASMI) was calculated using the formula: ASMI = ASM/height². Nondominant handgrip strength (ND-HGS) was measured by using a digital dynamometer. The diagnostic criteria for sarcopenia were defined as follows: ASMI ≤7 kg/m² and ND-HGS ≤25 kg. Kaplan-Meier survival curve showed that sarcopenia was significantly associated with worse prognosis (P<0.001).

US

In a study by Tandon et al. (17), a total of 152 cirrhotic patients were included. The diagnostic criteria for sarcopenia were the same as the Montano-Loza’s study. SMI was measured by using CT or MRI and right thigh muscle thickness was measured by using bedside US. The results showed that thigh muscle measured by US positively correlated with SMI.

Conclusions

Sarcopenia is an accurate and sensitive marker for evaluating malnutrition. Regardless of diagnostic methods and criteria, it is an independent prognostic factor in patients waiting for or undergoing liver transplantation. However, it remains uncertain about which imaging tool and method for diagnosing sarcopenia is the most optimal. First, no study compares the prognostic accuracy among CT, MRI, DEXA, and US. Second, MRI and US may avoid the risk of high radiation exposure, but specific methods for measuring sarcopenia based on MRI and US are insufficient. Third, it is not clear which plane and skeletal muscle is more reliable and accurate for reflecting the severity of sarcopenia and therefore for predicting outcomes. Fourth, the software for analyzing the images, such as SlimOmatic, MATLAB, ImageJ, and MITK, are expensive and complicated. A more simple and easy-to-perform method is needed.

Acknowledgements

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Eric M. Yoshida,Trana Hussaini) for the series “Liver Transplantation” published in AME Medical Journal. The article has undergone external peer review.

Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/amj.2018.01.02). The series “Liver Transplantation” was commissioned by the editorial office without any funding or sponsorship. Dr. Qi serves as an Editor-in-Chief of AME Medical Journal. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010;53:397-417. [Crossref] [PubMed]
2. Deng H, Qi X, Guo X. Computed tomography for the diagnosis of varices in liver cirrhosis: a systematic review and meta-analysis of observational studies. Postgrad Med 2017;129:318-28. [Crossref] [PubMed]
3. Wang R, Qi X, Guo X. Quantification of ascites based on abdomino-pelvic computed tomography scans for predicting the in-hospital mortality of liver cirrhosis. Exp Ther Med 2017;14:5733-42. [PubMed]
4. Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646-9. [Crossref] [PubMed]
5. Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000;31:864-71. [Crossref] [PubMed]
6. Peng Y, Qi X, Guo X. Child-Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies. Medicine (Baltimore) 2016;95:e2877 [Crossref] [PubMed]
7. Lee SJ, Janssen I, Heymsfield SB, et al. Relation between whole-body and regional measures of human skeletal muscle. Am J Clin Nutr 2004;80:1215-21. [PubMed]
8. Durand F, Buyse S, Francoz C, et al. Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography. J Hepatol 2014;60:1151-7. [Crossref] [PubMed]
9. van Vugt JL, Levolger S, de Bruin RW, et al. Systematic Review and Meta-Analysis of the Impact of Computed Tomography-Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation. Am J Transplant 2016;16:2277-92. [Crossref] [PubMed]
10. Kalafateli M, Mantzoukis K, Choi Yau Y, et al. Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score. J Cachexia Sarcopenia Muscle 2017;8:113-21. [Crossref] [PubMed]
11. Englesbe MJ, Patel SP, He K, et al. Sarcopenia and mortality after liver transplantation. J Am Coll Surg 2010;211:271-8. [Crossref] [PubMed]
12. Masuda T, Shirabe K, Ikegami T, et al. Sarcopenia is a prognostic factor in living donor liver transplantation. Liver Transpl 2014;20:401-7. [Crossref] [PubMed]
13. Montano-Loza AJ, Meza-Junco J, Prado CM, et al. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 2012;10:166-73, 173.e1.
14. Tandon P, Ney M, Irwin I, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl 2012;18:1209-16. [Crossref] [PubMed]
15. Praktiknjo M, Book M, Luetkens J, et al. Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis. Hepatology 2017; [Epub ahead of print]. [Crossref] [PubMed]
16. Belarmino G, Gonzalez MC, Sala P, et al. Diagnosing Sarcopenia in Male Patients With Cirrhosis by Dual-Energy X-Ray Absorptiometry Estimates of Appendicular Skeletal Muscle Mass. JPEN J Parenter Enteral Nutr 2017;148607117701400 [PubMed]
17. Tandon P, Low G, Mourtzakis M, et al. A Model to Identify Sarcopenia in Patients With Cirrhosis. Clin Gastroenterol Hepatol 2016;14:1473-1480.e3. [Crossref] [PubMed]