Silva TF, Loschi TM, Boteon APCS, Boteon YL. Imaging-based assessment of sarcopenia in liver transplant candidates: A systematic review. World J Gastroenterol 2025; 31(43): 112076 [DOI: 10.3748/wjg.v31.i43.112076]
Corresponding Author of This Article
Yuri L Boteon, MD, PhD, FACS, Professor, Transplant Centre, Hospital Israelita Albert Einstein, 627/701 Albert Einstein Avenue, Sao Paulo 05652-900, Brazil. yuri.boteon@einstein.br
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Systematic Reviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Thaynara Flosi Silva, Thais Mellato Loschi, Amanda P C S Boteon, Yuri L Boteon, Transplant Centre, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil
Thaynara Flosi Silva, Yuri L Boteon, Faculdade Israelita de Ciências da Saúde Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo 05652-900, Brazil
Author contributions: Boteon YL, Boteon APCS, and Silva TF conceived the idea and designed the study; Silva TF and Loschi TM performed the literature search and analyzed the data; Silva TF and Boteon YL drafted the manuscript; Boteon APCS and Boteon YL performed the critical revision of the manuscript for intellectual content, and supervision of the study process. All authors reviewed the draft, contributed to editing and approved the final manuscript version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yuri L Boteon, MD, PhD, FACS, Professor, Transplant Centre, Hospital Israelita Albert Einstein, 627/701 Albert Einstein Avenue, Sao Paulo 05652-900, Brazil. yuri.boteon@einstein.br
Received: July 17, 2025 Revised: September 23, 2025 Accepted: October 23, 2025 Published online: November 21, 2025 Processing time: 126 Days and 18.8 Hours
Abstract
BACKGROUND
Sarcopenia is prevalent among patients with end-stage liver disease (ESLD) and is associated with adverse outcomes both before and after liver transplantation (LT). Accurate assessment of muscle mass is essential for effective risk stratification and optimization of transplant outcomes.
AIM
To identify imaging modalities used to assess sarcopenia in ESLD patients awaiting LT, and evaluate the clinical utility of each technique in predicting waitlist mortality, length of hospital stay, and post-transplant survival.
METHODS
A systematic search was conducted in PubMed, MEDLINE, EMBASE, and Scopus for studies published between May 2015 and May 2025. Eligible studies included original research evaluating sarcopenia using imaging techniques in ESLD patients listed for LT. Due to heterogeneity in study design, diagnostic criteria, and outcomes, data were synthesized qualitatively.
RESULTS
A total of 17 studies met the inclusion criteria, encompassing modalities such as computed tomography (CT), magnetic resonance imaging, dual-energy X-ray absorptiometry, and ultrasound. CT at the third lumbar vertebra level was most frequently used, exhibiting consistent prognostic values for pre- and post-transplant outcomes. However, considerable variability in cutoff values and sarcopenia definitions was observed. Emerging evidence also supports the prognostic relevance of muscle quality indicators, including muscle attenuation and fat infiltration.
CONCLUSION
CT and magnetic resonance imaging are the most robust imaging methods for sarcopenia diagnosis in patients with ESLD. Standardized diagnostic criteria incorporating muscle quality metrics are essential for improving prognostic accuracy and guiding clinical decision making in LT candidates. Such integration would also support the development of unified frameworks for sarcopenia assessment in transplantation practice.
Core Tip: Sarcopenia is a major prognostic factor in patients with end-stage liver disease awaiting liver transplantation. This systematic review highlights computed tomography and magnetic resonance imaging as the most accurate modalities for assessing skeletal muscle mass, especially at the third lumbar vertebra level. Despite this predictive value, the lack of standardized diagnostic criteria and cutoff values limits clinical application. This study emphasizes the emerging role of muscle quality indicators and calls for international consensus to improve risk stratification, guide clinical decision making, and enhance transplant outcomes.
Citation: Silva TF, Loschi TM, Boteon APCS, Boteon YL. Imaging-based assessment of sarcopenia in liver transplant candidates: A systematic review. World J Gastroenterol 2025; 31(43): 112076
Liver transplantation (LT) is the only treatment with curative potential for end-stage liver disease (ESLD)[1]. Sarcopenia, a condition affecting 30%-70% of patients with ESLD, is highly prevalent among LT candidates and represents a significant challenge in clinical management[2]. Sarcopenia is a progressive muscle disorder characterized by concurrent reductions in muscle quantity, overall muscle strength, and muscle strength relative to size (i.e., specific muscle strength)[3]. Initially characterized as an age-related decline[4], sarcopenia is now recognized in other populations, including individuals with chronic diseases, physical inactivity, and malnutrition[5,6]. Affected patients exhibit markedly reduced survival rates, with sarcopenia associated with a 1.58-fold increase in post-LT mortality risk, underscoring its strong prognostic value in this population[7,8]. Diagnosis centers on a combination of imaging-based assessments of muscle mass and tests of muscle strength and/or physical performance[7,9].
Despite its recognized prognostic value, the lack of consensus on optimal diagnostic criteria and imaging techniques for assessing sarcopenia in patients with ESLD remains a major barrier to effective clinical management. Several imaging modalities, including ultrasonography (US)[10-12], computed tomography (CT)[13,14], magnetic resonance imaging (MRI)[15], and dual-energy X-ray absorptiometry (DXA)[16], are used to evaluate body composition in chronic liver disease. Compared with strength or physical performance tests, imaging-derived muscle mass measurements are less influenced by acute illness or cognitive impairment, rendering them more suitable for objective clinical assessments[17].
Thus, identifying the most effective imaging modalities for evaluating sarcopenia, and elucidating any correlations with clinically meaningful outcomes, is essential to improving patient care and transplant prognosis. This study aims to identify imaging methods for evaluating sarcopenia in patients with ESLD awaiting LT and evaluate the clinical utility of each method in predicting outcomes such as waitlist mortality, length of hospital stay, and post-transplant survival.
MATERIALS AND METHODS
This systematic review was conducted in accordance with the PRISMA guidelines[18]. No review protocol was registered prior to initiation.
Literature search strategy and data sources
PubMed, MEDLINE, EMBASE, and Scopus were searched using the keyword “sarcopenia” in combination with the free-text terms “end-stage liver disease”, “radiologic evaluation”, “ultrasonography”, “computed tomography”, “magnetic resonance imaging”, and “photon absorptiometry”. Only studies published within the last 10 years (between May 2015 and May 2025) were included. The search was completed in May 2025. The complete search strategy for one database is outlined in Supplementary Table 1.
Study screening and selection
Two authors (Flosi TS and Loschi TM) independently screened and selected studies using an Excel spreadsheet. There were no discrepancies in study selection. Titles outside the scope of this review were excluded. Abstracts were then evaluated, and those deemed irrelevant were excluded. The remaining articles were assessed in full-text form for eligibility. The selection process is illustrated in Figure 1.
Figure 1 Study flow diagram of study selection for the systematic review of imaging methods used to diagnose sarcopenia in patients with end-stage liver disease awaiting liver transplantation.
Following literature search titles were screened. The selected abstracts were read, and duplicate articles, non-clinical studies, or reports unrelated to the review’s objective were excluded. Seventeen studies met the inclusion criteria and were included in the final synthesis.
Eligibility criteria
The inclusion criteria were as follows: Studies evaluating sarcopenia in patients with ESLD who were candidates for LT; studies using imaging modalities to assess sarcopenia; and articles written and published in English. The exclusion criteria were as follows: Studies involving patients with early- or intermediate-stage liver disease, or those not eligible for LT; studies assessing sarcopenia using non-imaging methods; opinion articles, reviews, editorials, letters, and comments; and articles not written in English.
Data extraction and outcome measures
The following data were extracted from each included study: First author, year of publication, study design, country of origin/ethnicity, number of participants, age and sex distribution, and etiology of liver disease. Imaging modalities, acquisition protocols, cutoff values, timing of imaging, sarcopenia prevalence, and associations with clinical outcomes were also analyzed. Primary outcomes included survival rates, post-transplant mortality, length of hospital and intensive care unit (ICU) stay, bacterial infections, and hospital costs. Studies were critically evaluated based on design, methodology, and reported outcomes.
Study quality and certainty of evidence
Study quality was assessed using the Newcastle-Ottawa Scale (NOS)[19], an adapted version of which was applied to cross-sectional studies, considering selection, comparability, and outcome domains[20]. Studies with a score of over seven points were deemed high quality; greater emphasis was placed on findings from these studies. Overall confidence in the evidence was based on study quality and the consistency of results, although no formal grading system was applied. No assumptions or data simplifications were made.
Effect measures
Due to the descriptive nature of this study, pooled effect estimates were not calculated. Where reported, measures of association, such as hazard ratios, odds ratios, and correlation coefficients, were presented as described in the original studies.
Synthesis methods
Qualitative synthesis was conducted due to the heterogeneity in study design, diagnostic approaches to sarcopenia, and outcome reporting of the included studies. Data were extracted and organized into text and summary tables outlining population characteristics, sarcopenia assessment methods (imaging modalities, cutoff values, timing), prevalence, and clinical outcomes. The synthesis followed the framework proposed by Popay et al[21], which involves descriptive summarization, exploration of relationships among findings, and evaluation of evidence strength and consistency. This method ensures structured, transparent interpretation of findings without statistical pooling. Variations in imaging techniques (CT, DXA, MRI, US) and sarcopenia definitions were identified as key sources of heterogeneity. Results are presented narratively and supported by tabular data.
RESULTS
A total of 17 articles met the inclusion criteria for this study. Figure 1 summarizes the screening process. The sample sizes of the included studies ranged from 18 to 469 participants, with mean patient ages varying between 52 and 59.6 years. The most frequent indications for LT were chronic viral hepatitis (hepatitis B and/or C virus), representing 30%-35% of cases, and alcohol-related liver disease, accounting for 20%-30%. Metabolic dysfunction-associated steatotic liver disease comprised 10%-12%. Autoimmune and cholestatic diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) accounted for 10%-15%. Hepatocellular carcinoma was the indication in 15%-20% of recipients; however, there may have been overlap with cirrhotic etiologies. Cryptogenic cirrhosis and other unspecified causes comprised 5%-10%. Less common indications included acute liver failure (5%-7%) and retransplantation (5%). Rare causes such as human immunodeficiency virus-related disease, drug toxicity, and cholangiocarcinoma were reported sporadically and together represented < 3% of cases. Pediatric etiologies such as hepatoblastoma were not represented, consistent with the exclusively adult populations analyzed. Regarding methodological quality, two studies were rated as moderate quality (NOS scores < 7), 2 as good quality, and 13 as high quality (NOS scores ≥ 7) (Supplementary Table 2). A graphical overview of the study quality appraisal is provided in Supplementary Figure 1. Detailed characteristics of all included studies are presented in Table 1.
Table 1 Summary of study design, participant demographics, and methodological quality (Newcastle-Ottawa scale score) for the 17 studies.
Imaging methods for assessing sarcopenia in patients with ESLD
Several imaging modalities were employed to assess skeletal muscle mass in patients with ESLD, with CT the most frequently used. CT was utilized in 13 of the 17 studies[22-38], predominantly at the third lumbar vertebra (L3) level, to quantify the skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle area, and muscle attenuation (MA). The most frequently adopted SMI cutoff values were < 50 cm2/m2 for males and < 39 cm2/m2 for females, although some studies used alternative thresholds (e.g., 48.9 cm2/m2 or sex-specific quartiles). PMI cutoffs also varied; for example, one study defined sarcopenia as < 5.1 cm2/m2 for males and < 4.3 cm2/m2 for females.
DXA was used in three studies[22,29,36], with indices such as the appendicular lean mass index (ALMI) or SMI applied. Typical cutoffs were < 7.26 kg/m2 for males and between < 5.45 kg/m2 and < 5.5 kg/m2 for females. US was employed in two studies[22,26], targeting specific muscle groups such as the vastus lateralis, quadriceps, and upper/Lower limbs. Despite its accessibility, US is limited by operator dependence and technique variability.
MRI was used in two studies[24,26]. One study employed whole-body segmentation and muscle fat infiltration indices; the other incorporated 31P magnetic resonance spectroscopy to assess intramyocellular pH and adenosine triphosphate metabolism. One study also applied bioelectrical impedance spectroscopy, using cutoffs of ≤ 8.50 kg/m2 for males and ≤ 5.75 kg/m2 for females. Overall, CT remains the gold standard due to its routine use and established prognostic cutoffs. A complete overview of imaging techniques and diagnostic thresholds is provided in Table 1. The relative distribution of modalities across the included studies is illustrated in Supplementary Figure 2.
Waitlist mortality
Five studies investigated the association between sarcopenia and mortality in patients on the LT waiting list[25,29,30,34,35]. Sarcopenia prevalence ranged from 22%-50%, depending on the diagnostic method and cutoff used. Four of the five studies reported a significant association between sarcopenia and increased mortality. An increase of 1 cm2/m2 in SMI was associated with a 5% reduction in mortality risk[25], and a 1 kg/m2 increase in ALMI linked to a 22% reduction[29]. Sex-specific analyses demonstrated that low SMI significantly predicted mortality in both males and females; PMI was predictive only in females[34]. However, one study found no significant association between PMI and waitlist mortality, indicating that PMI may not be a reliable surrogate for total muscle mass in this context[35]. These findings highlight sarcopenia as a key prognostic factor in patients with ESLD awaiting LT and support the incorporation of standardized imaging-based assessments in clinical practice (Table 2).
Table 2 Association between sarcopenia and waitlist mortality in end-stage liver disease: Summary of prevalence rates, effect measures, and outcomes from studies evaluating the impact of sarcopenia on waitlist mortality among patients with end-stage liver disease.
HR per 1 cm2/m2 increase = 0.95 (95%CI: 0.92-0.98), P < 0.001, meaning a 5% risk reduction per unit increase in SMI; lower SMI indicates higher mortality risk
HR per 1 kg/m2 increase in ALMI = 0.78 (95%CI: 0.62-0.98), P = 0.03. Indicates a 22% reduction in waitlist mortality risk with each unit increase in ALMI; sarcopenia is associated with increased risk
Female: Both low SMI and PMI significant; male: Low SMI significant and PMI not significant
HR
Sarcopenia defined by SMI was significantly associated with increased waitlist mortality in both male (HR = 2.46, 95%CI: 1.38-4.39; P = 0.002) and female (HR = 2.05, 95%CI: 1.00-4.21; P = 0.05). Sarcopenia defined by PMI was significantly associated with mortality in females (HR = 2.47; 95%CI: 1.24-4.95; P = 0.01), but not in males (HR = 0.85; P = 0.09)
Six studies investigated the relationship between sarcopenia and post-transplant survival[23,27,31-33,38]. Sarcopenia prevalence prior to transplantation varied from 22%-61%, depending on the diagnostic criteria and assessment timing. Most studies reported a significant association between sarcopenia (or perioperative muscle mass loss) and poorer post-transplant survival. For instance, sarcopenia defined by psoas muscle area (PMA) was linked to lower short- and long-term survival rates[27]. Similarly, a large perioperative reduction in SMI was significantly associated with decreased survival[31]. One study did not find a significant association between sarcopenia and survival but identified abnormal muscle metabolism and myosteatosis as stronger predictors of long-term outcome[32]. Male patients with sarcopenia exhibited significantly higher post-transplant mortality, even after adjustment for confounders[38]. These results emphasize the importance of evaluating both muscle quantity and quality when assessing post-transplant prognosis in patients with ESLD (Table 3).
Table 3 Association between sarcopenia and post-transplant survival in end-stage liver disease: Summary of sarcopenia prevalence, statistical associations, and survival outcomes reported in studies assessing post-liver transplantation prognosis in end-stage liver disease patients.
Myosteatosis predicted worse survival: 3 months (72% vs 95%), 1 year (63% vs 90%), 5 years (54% vs 84%), P = 0.001. SMI decreased post-LT but was not associated with survival
Sarcopenia, defined by psoas muscle area (cutoffs: < 1561 mm2 for male, < 1464 mm2 for female), was associated with lower post-LT survival, 1-year survival 59% vs 94%, and 5-year survival 54% vs 80% (log-rank P < 0.001)
1 year pre-LT: 77.8%. Pre-LT: 98.6%. Post-LT: 100%
Significant
HR
A large preoperative decrease in SMI (ΔSMI ≤ -30%) was significantly associated with reduced post-LT survival, HR = 0.284 (95%CI: 0.102-0.789), P = 0.016
Male with sarcopenia had significantly higher post-LT mortality at 1 and 3 years. Sarcopenia was independently associated with increased risk of mortality after adjustment for MELD and liver disease etiology (univariable HR = 3.65, 95%CI 1.29-10.28, P = 0.01; multivariable HR = 4.39, P = 0.007)
Two studies evaluated the association between sarcopenia and the length of ICU and hospital stays in patients with ESLD undergoing LT[28,36]. Sarcopenia prevalence ranged from 15%-28%, depending on sex and the body composition assessment method employed (CT or DEXA). One study found that patients in the lowest SMI quartile were significantly more likely to experience prolonged hospital stays (> 3 weeks); MA was not significantly associated with the length of ICU/hospital stay[28]. The second study reported that reduced upper limb lean mass as measured by DEXA was inversely associated with ICU and hospital stay duration in men. Sarcopenia as defined by ALMI cutoffs did not show a significant association with these outcomes[36]. These findings suggest that specific muscle composition parameters, particularly those reflecting muscle quality and regional lean mass distribution, may be more sensitive indicators of postoperative resource utilization in LT recipients (Table 4).
Table 4 Association between sarcopenia and intensive care unit/hospital length of stay in end-stage liver disease: Summary of effect measures and findings from studies assessing the relationship between sarcopenia and the duration of intensive care unit and hospital stays in liver transplant candidates.
SMI: Significant with hospital stay; not significant with ICU stay. MA: Not significant
OR
Length of ICU stay > 3 days was not significantly associated with SMI (OR = 1.44; 95%CI: 0.48-4.36; P = 0.518) or MA (OR = 0.45; 95%CI: 0.15-1.27; P = 0.155). Total hospital stays > 3 weeks was significantly associated with higher SMI (OR = 0.21; 95%CI: 0.06-0.73; P = 0.014), but not with MA (OR = 0.41; 95%CI: 0.13-1.27; P = 0.122)
Upper limb lean mass: Significant (male), not significant (female); sarcopenia (APLM cutoffs): Not significant
τb
Upper limb lean mass was inversely associated with ICU stay (τb = -0.090, P = 0.015) and hospital stay (τb = -0.10, P = 0.0078). Sarcopenia based on gender-specific cutoffs showed no significant association with length of ICU or hospital stays
This systematic review identified considerable heterogeneity in imaging modalities, diagnostic thresholds, and clinical applications used to assess sarcopenia in patients with ESLD awaiting LT. Despite methodological differences, most studies confirmed that sarcopenia, particularly when assessed using CT at L3, is associated with increased waitlist mortality, poorer post-transplant survival, and longer hospital stays. These findings underscore the prognostic relevance of muscle mass assessment and the need for standardized, imaging-based diagnostic criteria to improve risk stratification and clinical management of this population.
Sarcopenia, a progressive and generalized loss of skeletal muscle mass and function, is highly prevalent in patients with ESLD[39-41]. CT and MRI are considered the gold standard modalities for skeletal muscle mass evaluation in this context. Their capacity to differentiate muscle from fat and other soft tissues enables precise quantification of body composition[9,42]. Most studies in this review utilized CT, particularly at L3, to calculate indices such as SMI, PMI, and MA. This anatomical landmark is extensively validated, as the cross-sectional area of muscle at L3 strongly correlates with total skeletal muscle mass[43].
The L3 SMI, calculated by normalizing the total muscle area at this level to the body surface area (cm2/m2), was the most frequently applied parameter. Cutoff values of < 50 cm2/m2 for males and < 39 cm2/m2 for females were frequently used to define sarcopenia in transplant candidates[25]; however, variations reflecting population-specific characteristics were observed. For example, the Japanese Society of Hepatology recommends lower thresholds (SMI < 42 cm2/m2 for males and < 38 cm2/m2 for females)[44], highlighting the importance of tailored diagnostic criteria.
Several studies utilized the isolated PMA at L3 as an alternative metric. The PMA has gained popularity due to its simplicity and clinical feasibility; in some studies, it demonstrated superior post-transplant survival predictive value compared with more complex indices[27]. However, the findings of this review indicate limitations to PMI/PMA in certain contexts; one study, for example, reported no significant associations between PMI and waitlist mortality[35], raising questions about its generalizability as a sarcopenia marker.
Other imaging techniques such as DXA, bioelectrical impedance analysis (BIA), and US were used less frequently and showed mixed results. DXA, applied in three studies, provided reasonable lean body mass estimates with established thresholds (e.g., ALMI < 7.26 kg/m2 for males); however, its clinical utility may be limited by accessibility. US and BIA offer advantages in terms of cost and the lack of exposure to radiation; however, their lower precision, especially with the fluid shifts and edema common in cirrhosis, limits their standalone reliability[11,45,46]. Accordingly, these modalities may be better suited to longitudinal monitoring or resource-limited settings where CT or MRI are not feasible.
A key clinical implication of this study is the impact of sarcopenia on waitlist and post-transplant outcomes. Multiple studies confirmed that low muscle mass is an independent predictor of mortality prior to transplantation, with even small increases in SMI or ALMI significantly reducing mortality risk[25,29]. Post transplant, sarcopenia was consistently associated with lower survival rates, with perioperative muscle loss linked to poor outcomes in some studies[31,38]. Interestingly, one study suggested that abnormal muscle metabolism and fat infiltration (i.e., myosteatosis) may be stronger predictors than muscle mass alone[32]. This aligns with growing evidence that muscle quality, not merely quantity, is essential to understanding patient frailty and resilience. Two studies reported that sarcopenia, particularly when evaluated using regional metrics such as upper limb lean mass, may influence the length of ICU and hospital stay[28,36]. This highlights the potential role of body composition analysis in forecasting healthcare resource utilization, postoperative recovery, and rehabilitation needs.
Despite these insights, significant methodological inconsistencies across the included studies limit comparability and generalizability. Sarcopenia definitions, imaging techniques, and muscle groups analyzed varied widely. Additional heterogeneity arises from the cutoff values applied to define sarcopenia. Studies using the widely adopted thresholds of < 50 cm2/m2 for males and < 39 cm2/m2 for females[25,34] consistently reported strong associations between waitlist mortality and post-transplant survival. Alternative definitions such as the lower thresholds by the Japanese Society of Hepatology (< 42 cm2/m2 and < 38 cm2/m2) and quartile-based cutoffs often yielded different prevalence estimates, and, in some cases, attenuated associations with outcomes[30,35]. Similarly, PMI thresholds had a less consistent prognostic value, with some cohorts reporting significant associations only in females[34] and others finding no predictive value[35]. This underscores the critical impact of threshold choice on prevalence estimates and prognostic performance, and reinforces the need for consensus definitions validated across populations. This heterogeneity hampers cross-study interpretation and limits the translation of findings to clinical practice. There is a clear need for international consensus guidelines to standardize imaging protocols, measurement sites, diagnostic thresholds, and reporting formats for sarcopenia assessment in liver disease[47].
Beyond methodological heterogeneity, there exist intrinsic limitations of imaging-based sarcopenia assessment. First, sarcopenia only partially captures the broader construct of frailty, which encompasses muscle strength, physical performance, and other domains not measurable by imaging. As a result, reliance on cross-sectional muscle indices may underestimate functional impairment in some patients. Second, locoregional and interethnic variations in muscle mass distribution and body composition complicate the generalizability of diagnostic thresholds. For example, cutoffs validated in Asian cohorts (e.g., the Japanese Society of Hepatology criteria) are typically lower than those applied in Western populations, reflecting anthropometric differences. Finally, the choice of indices (SMI, ALMI, PMA) can significantly alter prevalence estimates and prognostic associations. SMI at L3 remains the most validated metric; simpler measures such as PMA may fail to capture total muscle mass or muscle quality, limiting comparability across studies. These limitations highlight the need for the integration of imaging data with functional assessments, and the development of population-specific reference standards through international consensus efforts.
This study has further limitations from a methodological perspective. The protocol was not prospectively registered in PROSPERO or elsewhere, which may reduce transparency and reproducibility despite strict adherence to PRISMA guidelines. Moreover, the search was restricted to four major bibliographic databases (PubMed, MEDLINE, EMBASE, Scopus), without the inclusion of grey literature, trial registries, or conference abstracts. This may have introduced publication bias, as negative/null results are less likely to appear in indexed journals. While this strategy ensured consistency and focus on peer-reviewed data, future reviews should incorporate additional sources to improve comprehensiveness and reduce potential bias.
It is important to note that while methodological quality varied across the included studies, most were rated as high quality (13 of 17 studies with NOS ≥ 7). Accordingly, the narrative synthesis placed greater emphasis on these studies when interpreting prognostic associations between sarcopenia and outcomes. Findings from moderate-quality studies were included for completeness but should be interpreted cautiously. Weighting the conclusions toward the strongest evidence increased confidence that the observations, particularly the impact of CT-assessed sarcopenia at L3 on waitlist mortality and post-transplant survival, were valid and clinically meaningful. This study underscores the growing importance of muscle quality metrics such as density (via CT attenuation), fat infiltration (myosteatosis), and metabolic markers (via spectroscopy) as more sensitive outcome predictors. Future research should aim to validate composite sarcopenia measures incorporating structural and functional muscle attributes.
Beyond sarcopenia, additional confounding variables may influence outcomes in LT candidates. Factors such as age, comorbidities (e.g., diabetes, chronic kidney disease), and baseline nutritional status have been shown to modulate sarcopenia severity and post-transplant prognosis[48,49]. Moreover, institutional characteristics, including the volume and experience of the transplant center, impact surgical outcomes and survival, independent of patient-level variables[50]. While most studies included in this study adjusted for model for ESLD or Child-Pugh scores and some clinical covariates, only a few comprehensively accounted for this broader range of potential confounders. Future studies should adopt multivariable models incorporating age, comorbidity burden, nutritional metrics, and center-level factors to more accurately isolate the prognostic role of sarcopenia and enable risk-adjusted comparisons across populations. Finally, while LT reverses liver dysfunction, sarcopenia may persist, or develop de novo, after transplantation[51]. Immunosuppressive therapy, metabolic complications, physical inactivity, and infections may all contribute to this. Post-transplant sarcopenia has been linked to reduced survival[52], emphasizing the need for continued monitoring and targeted interventions throughout the transplant continuum.
Based on the evidence synthesized in this study, we propose that a standardized approach to sarcopenia assessment in LT candidates should prioritize CT or MRI evaluation at the L3 level, given the reproducibility, validation against whole-body muscle mass, and routine availability in this population. The SMI, normalized to height or body surface area, should be the primary diagnostic metric, with sex-specific cutoffs of < 50 cm2/m2 for males and < 39 cm2/m2 for females. These were the most consistently applied thresholds across the included studies and are endorsed by international hepatology and oncology societies. Where CT attenuation data are available, the inclusion of muscle quality measures (e.g., myosteatosis, density) should be encouraged, as they provide prognostic information beyond muscle mass alone. Alternative modalities such as DEXA, BIA, and US may serve as adjuncts in longitudinal monitoring or settings where cross-sectional imaging is unavailable. However, these should not replace CT/MRI as reference methods. Finally, standardized diagnostic criteria should not only incorporate quantitative cutoffs but also report changes over time (e.g., perioperative ΔSMI), as dynamic loss of muscle mass has emerged as a clinically relevant outcome predictor. The adoption of these methodological standards could improve comparability across studies and facilitate the integration of sarcopenia assessment into routine transplant evaluations.
Given the consistent association observed between sarcopenia and increased waitlist mortality[25,29,34], we recommend the incorporation of imaging-based skeletal muscle mass assessments in the evaluation and prioritization of candidates on LT waiting lists. Integration of sarcopenia metrics alongside established scores such as model for ESLD-Na could refine risk stratification, identify high-risk patients who may benefit from timely transplantation, and support more equitable allocation decisions. While further prospective validation is needed, current evidence justifies considering sarcopenia as an adjunct prognostic marker in candidate selection.
In summary, CT and MRI remain the most robust and validated methods for assessing sarcopenia in patients with ESLD. Imaging-based sarcopenia diagnosis provides key prognostic information and should be integrated into pre- and post-transplant evaluations. Standardization of measurement protocols and cutoffs, along with the incorporation of muscle quality metrics, is essential to improving patient care. Future research should focus on longitudinal monitoring, intervention development, and validation of comprehensive diagnostic criteria which capture the multifaceted nature of sarcopenia in LT.
CONCLUSION
Sarcopenia is a highly prevalent and clinically impactful condition in patients with ESLD, with key implications for both pre- and post-transplant outcomes. This systematic review indicates that imaging-based assessment, particularly using CT and MRI at the L3 level, may be the most reliable method currently available for evaluating skeletal muscle mass in this population. However, considerable heterogeneity in diagnostic criteria, measurement techniques, and cutoff values limits comparability across studies and precludes immediate clinical standardization. Future research should focus on prospective validation and the development of international consensus guidelines to harmonize sarcopenia assessment and reporting. Incorporating muscle quality measures, such as fat infiltration and muscle density, may ultimately enhance prognostic accuracy and support more personalized care for LT candidates.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: International Liver Transplantation Society.
Specialty type: Gastroenterology and hepatology
Country of origin: Brazil
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade B
Novelty: Grade B, Grade B, Grade C
Creativity or Innovation: Grade B, Grade B, Grade C
Scientific Significance: Grade B, Grade B, Grade C
P-Reviewer: Alnagar A, PhD, United Kingdom; Lee YY, Consultant, FRCS, Lecturer, Singapore; Torun M, MD, PhD, Türkiye S-Editor: Wu S L-Editor: A P-Editor: Yu HG
Kirk B, Cawthon PM, Arai H, Ávila-Funes JA, Barazzoni R, Bhasin S, Binder EF, Bruyere O, Cederholm T, Chen LK, Cooper C, Duque G, Fielding RA, Guralnik J, Kiel DP, Landi F, Reginster JY, Sayer AA, Visser M, von Haehling S, Woo J, Cruz-Jentoft AJ; Global Leadership Initiative in Sarcopenia (GLIS) group. The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).Age Ageing. 2024;53:afae052.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 29][Cited by in RCA: 219][Article Influence: 219.0][Reference Citation Analysis (0)]
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis.Age Ageing. 2019;48:16-31.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 6646][Cited by in RCA: 8216][Article Influence: 1369.3][Reference Citation Analysis (1)]
Moctezuma-Velazquez C, Ebadi M, Bhanji RA, Stirnimann G, Tandon P, Montano-Loza AJ. Limited performance of subjective global assessment compared to computed tomography-determined sarcopenia in predicting adverse clinical outcomes in patients with cirrhosis.Clin Nutr. 2019;38:2696-2703.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 23][Cited by in RCA: 35][Article Influence: 5.8][Reference Citation Analysis (0)]
Popay J, Roberts H, Sowden A, Petticrew M, Arai L, Rodgers M, Britten N, Roen K, Duffy S.
Guidance on the Conduct of Narrative Synthesis in Systematic Reviews: A product from the ESRC Methods Programme. Lancaster, Unite Kingdom: University of Lancaster, 2006.
[PubMed] [DOI] [Full Text]
Molwitz I, Recklies F, Stark M, Horvatits T, Salamon J, Huber S, Fischer L, Adam G, Lohse AW, Sterneck M, Horvatits K. Muscle quality determined by computed tomography predicts short-term and long-term survival after liver transplantation.Sci Rep. 2023;13:7631.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 9][Reference Citation Analysis (0)]
Forsgren MF, Pine S, Harrington CR, Gregory D, Petersson M, Rinella M, Leinhard OD, VanWagner LB. Body composition and muscle composition phenotypes in patients on waitlist and shortly after liver transplant - results from a pilot study.BMC Gastroenterol. 2024;24:356.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 2][Reference Citation Analysis (0)]
Quinlan JI, Dhaliwal A, Williams FR, Allen SL, Choudhary S, Rowlands A, Breen L, Lavery GG, Lord JM, Elsharkawy AM, Armstrong MJ, Greig CA. Impaired lower limb muscle mass, quality and function in end stage liver disease: A cross-sectional study.Exp Physiol. 2023;108:1066-1079.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 1][Cited by in RCA: 8][Article Influence: 4.0][Reference Citation Analysis (0)]
Alconchel F, Martínez-Alarcón L, Nicolás-López T, Khiri F, Febrero B, Cascales-Campos PA, Martínez-Insfran LA, Ríos A, Fernández-Hernández JA, Rodríguez JM, López-López V, Sánchez-Bueno F, Robles-Campos R, Parrilla P, Ramírez P. Psoas Muscle Index Does Not Predict Post-Transplant Outcomes: A Series of 57 Liver Transplant Recipients.Transplant Proc. 2020;52:549-552.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 2][Cited by in RCA: 6][Article Influence: 1.2][Reference Citation Analysis (0)]
van Vugt JLA, Buettner S, Alferink LJM, Bossche N, de Bruin RWF, Darwish Murad S, Polak WG, Metselaar HJ, IJzermans JNM. Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.Transpl Int. 2018;31:165-174.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 45][Cited by in RCA: 47][Article Influence: 5.9][Reference Citation Analysis (0)]
Dajti E, Rodrigues SG, Perazza F, Colecchia L, Marasco G, Renzulli M, Barbara G, Azzaroli F, Berzigotti A, Colecchia A, Ravaioli F. Sarcopenia evaluated by EASL/AASLD computed tomography-based criteria predicts mortality in patients with cirrhosis: A systematic review and meta-analysis.JHEP Rep. 2024;6:101113.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 1][Cited by in RCA: 9][Article Influence: 9.0][Reference Citation Analysis (0)]
