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The prognostic value of sarcopenia in acute-on-chronic liver failure: a systematic review and meta-analysis

BMC Gastroenterology volume 25, Article number: 300 (2025) Cite this article

Abstract

Background

Sarcopenia is prevalent in patients with chronic liver diseases, especially in cirrhosis patients. While sarcopenia is identified as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains unclear. This systematic review with meta-analysis aimed to explore the prognostic value of sarcopenia in ACLF patients.

Methods

A comprehensive online literature search was performed in Medline (via PubMed), Web of Science, Embase, and Cochrane Library, and eligible studies were screened according to the predetermined criteria. The quality of the included studies was assessed by using the revised Cochrane Collaboration Risk of Bias Tool for randomized-control studies and the Newcastle-Ottawa Quality Assessment Scale for observational studies. Available outcomes measured by odds ratio (OR), hazard ratio (HR), and risk ratio (RR) with a 95% confidence interval (CI) were extracted and further included in the meta-analysis. Stata (version 18.0) was used for all statistical analyses.

Results

Nine studies were included in further analysis. The pooled prevalence of sarcopenia was 53.3% (95% CI: 53.26 − 71.23%). The presence of sarcopenia was positively associated with 28-day mortality (HR = 2.11, 95% CI: 1.50–2.95, p < 0.001, I2 = 0.0%; OR = 2.73, 95% CI: 1.37–5.42, p = 0.004, I2 = 0.0%), 90-day mortality (HR = 1.66, 95% CI: 1.13–2.46, p = 0.01, I2 = 72.3%), and overall mortality (HR = 1.81, 95% CI: 1.30–2.51, p < 0.01, I2 = 0.0%). When using continuous variables to describe sarcopenia, a 1-unit increase in these indicators was almost significantly related to reduced 90-day mortality (HR = 0.98, 95% CI: 0.95-1.00, p = 0.052, I2 = 0.0%) and significantly associated with lower 1-year post-transplantation mortality (HR = 0.91, 95% CI: 0.85–0.98, p = 0.012, I2 = 32.7%).

Conclusion

Current evidence illustrates that sarcopenia is an unfavorable factor for both short- and long-term prognosis. More studies are needed to validate these findings in the future.

Peer Review reports

Introduction

Acute-on-chronic liver failure (ACLF) is a critical and life-threatening clinical syndrome that originated from chronic liver diseases (CLDs) and is characterized by the rapid decline of liver function and often accompanied with some severe complications such as jaundice, hepatorenal syndrome, and hepatic encephalopathy in a short period [1]. The main etiologies were different in that alcohol-related liver disease and bacterial infection occupy the majority in Western countries, as well as hepatitis B virus infection is the most common in Asia-Pacific regions [2]. ACLF is associated with a high risk of short-term mortality, with 25% and 40% in 28- and 90-day mortality rates, respectively [3]. Liver transplantation (LT) is the only curative treatment, however, due to the lack of liver donors, high cost, immune suppression, and post-LT complications (e.g., allograft dysfunction, infection, and biliary leak), ACLF-related death still poses a large burden [4, 5]. The prognosis prediction is crucial for ACLF, and some models have been developed to help clinicians with prognosis evaluation and guide donor liver allocation, such as the Model for End-stage Liver Disease [MELD] and MELD-Na. However, these models lack parameters to reflect the nutrition and physical status, which is vital but often ignored in ACLF risk assessment and treatment [6, 7]. A novel prognostic indicator associated with malnutrition and physical frailty is an urgent need.

Sarcopenia, a term derived from the Greek ‘sarco’(flesh) and ‘penia’(deficiency), is defined as a “progressive and generalized skeletal muscle disorder involving the accelerated loss of skeletal muscle mass and function”, and is a hallmark of malnutrition [8, 9]. The current consensuses of sarcopenia all consider low muscle mass as the central diagnostic criterion [10]. The prevalence of sarcopenia is extremely high in the population with CLDs [8, 11]. Recently, a large number of studies all indicated that the presence of sarcopenia related to poor clinical outcomes in various liver diseases (e.g., non-alcohol fatty liver disease, cirrhosis, and liver cancer) [11,12,13,14]. The prevalence of sarcopenia ranges from 30–70% in cirrhosis patients, who are at high risk of ACLF [1, 15] However, the prognostic value of sarcopenia in the ACLF population has only been evaluated in some cohort or case-control studies, and the conclusion is underexplored.

Therefore, we performed this systematic review and meta-analysis to calculate the prevalence of sarcopenia in ACLF and further assess the association between the presence of sarcopenia and ACLF.

Methods

Basic information

The meta-analysis was conducted and reported following the most recent Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines [16, 17]. The protocol was registered online in PROSPERO (registration ID: CRD42024594319, more information can be accessed via https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=594319).

Search strategy and selection criteria

Two researchers (SH and YW) independently and comprehensively searched Medline (via PubMed), Web of Science, Embase, and the Cochrane Library from inception to inception to November 13, 2024. The entire search terms were as follows: (sarcopenia OR skeletal muscle index OR muscle mass OR muscle strength OR muscle depletion OR muscle insufficiency) AND (ACLF OR acute-on-chronic liver failure OR chronic liver failure OR acute-on-chronic liver failure OR end-stage liver disease OR hepatic failure OR liver failure). The language of the included studies was limited to English.

The inclusion criteria were as follows: (i) case-control studies or retrospective and prospective cohort studies that reported the prognostic value of sarcopenia in ACLF; (ii) a clear definition of sarcopenia and ACLF; and (iii) data on mortality risk of sarcopenia in ACLF.

The exclusion criteria were as follows: (i) case report or case series consisting of fewer than 10 patients, narrative review, systematic review, and conference abstracts that duplicate original research findings; (ii) studies that did not define sarcopenia and ACLF clearly; (iii) studies that did not report direct outcomes.

Study outcomes

The primary outcome is the prevalence of sarcopenia in ACLF patients and the association between sarcopenia presence and mortality. Secondary outcomes are the association of sarcopenia (according to specific definitions and as a continuous value at CT measurement) with mortality and other clinical outcomes (e.g., cirrhosis incidence).

Data extraction and quality assessment

The following data from the individual studies were extracted: (i) basic information, including the first author, publication year, country, enrollment date, study design, sample size, and follow-up duration; (ii) sarcopenia definition and cut-off points; (iii) ACLF etiology, ACLF diagnosis criteria; (iv) available outcomes (odds ratio [OR], hazard ratio [HR], and risk ratio [RR]). If the outcomes were not reported directly in texts, GetData Graph Digitizer (version 2.26) would be used to extract data from figures [18]. Two researchers (SH and ZL) independently extracted the data, and disagreements were resolved by consensus with the third author (HZ). We used the revised Cochrane Collaboration Risk of Bias Tool (RoB 2) to evaluate the quality of randomized-control studies and the Newcastle-Ottawa Quality Assessment Scale (NOS) for the observational studies, where scores of 1 to 3, 4 to 6, and 7 to 9 were considered low, medium, and high quality, respectively [19, 20]. Two authors (SH and GS) independently assessed the quality of studies and disagreements were resolved by discussion.

Statistical analysis

Data analysis was performed using Stata software (version 18.0). The prevalence of sarcopenia was pooled as binomial proportions with 95% CIs after the Freeman-Tukey double arcsine transformation; differences between groups were tested using the random effects meta-regression method. The survival outcomes were characterized by OR, HR, or RR and related 95% confidence interval (CI). We used Q and I2 statistics to identify the internal heterogeneity among studies. The choice of fixed effects model or random effects model was determined by using the guidelines by Tufanuru et al. [21]. Regarding the publication bias, we used Egger’s test and Begg’s test for measurement. A two-sided p-value < 0.05 was defined as a statistical difference. When no meta-analysis could be conducted, we only described the study results.

Results

Search results and study selection

The study selection process was performed following the PRISMA flow diagram (Fig. 1). Eventually, nine articles covering 10 cohorts with 2,324 patients were included for further analysis [6, 22,23,24,25,26,27,28,29]. In particular, Mangana et al. investigated the outcomes with two separate baselines [27]. To maximize the sample size, two cohorts were considered to be contained in this study.

Fig. 1
figure 1

Flow chart of study retrieval

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Characteristics of the included studies

We enrolled nine cohort studies (seven retrospective cohorts and two prospective cohorts), and most of them (88.9%, 8/9) were single-center research. Six studies were conducted in Asia [6, 23,24,25,26, 29], two in Europe [22, 27], and one in South America [28]. The main etiologies for ACLF were alcohol, virus, and autoimmune. The diagnosis of ACLF was based on APASL criteria and EASL-CLIF criteria. Then, three approaches were utilized to define sarcopenia, consisting of the criteria by the Japanese Society of Hepatology (skeletal muscle index at the level of the third lumbar vertebra [L3-SMI] < 42 cm2/m2 in men and < 38 cm2/m2 in women) [30] (used by [6, 26]), the criteria by Carey et al. endorsed by EASL and AASLD (L3-SMI < 50 cm2/m2 for men and < 39 cm2/ m2 for women) [31] (used by [25, 27,28,29]), and the criteria by Kong et al. (L3-SMI ≤ 40.2 cm2/m2 in men and ≤ 31.6 cm2/m2 in women) [32] (used by [24]). Then, Artru et al. and Bai et al. used transversal right psoas muscle thickness at the umbilical level/height (TPMT/height), psoas muscle index (PMI), and L3-SMI as continuous variables to reflect sarcopenia, respectively [22, 23]. Most studies were evaluated to be considered as high quality by NOS score. The details of the nine articles and their corresponding quality assessment results are shown in Table 1 and S1.

Table 1 Characteristics of eligible studies in the meta-analysis
Full size table

Prevalence of sarcopenia in ACLF

The prevalence of sarcopenia in ACLF ranges from 12.17 to 92.86% in nine enrolled studies, and the pooled prevalence was 53.3% (95% CI: 53.26 − 71.23%) (Fig. 2). Significant heterogeneity was observed (I2 = 98.8%, p < 0.001).

Fig. 2
figure 2

The pooled prevalence of sarcopenia in ACLF patients

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Prognostic value of sarcopenia in ACLF

The presence of sarcopenia was positively associated with 28-day mortality (hazard ratio [HR] = 2.11, 95% CI: 1.50–2.95, p < 0.001, I2 = 0.0%; odds ratio [OR] = 2.73, 95% CI: 1.37–5.42, p = 0.004, I2 = 0.0%) [6, 27, 29], 90-day mortality (HR = 1.66, 95% CI: 1.13–2.46, p = 0.01, I2 = 72.3%) [6, 24, 26], and overall mortality (HR = 1.81, 95% CI: 1.30–2.51, p < 0.01, I2 = 0.0%) [28, 29] (Fig. 3A-D). When the indicators of sarcopenia were used as continuous variables, a 1-unit increase in these indicators was almost significantly related to reduced 90-day mortality (HR = 0.98, 95% CI: 0.95-1.00, p = 0.052, I2 = 0.0%) and significantly related to lower 1-year post-LT mortality (HR = 0.91, 95% CI: 0.85–0.98, p = 0.012, I2 = 32.7%) (Fig. 4A, B).

Fig. 3
figure 3

The association between the presence of sarcopania and (A) 28-day mortality; (B) 90-day mortality; (C) 1-year mortality; (D) 28-day mortality (measured by odds ratio)

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Fig. 4
figure 4

The association between sarcopenia valued by continuous variables and (A) 90-day mortality; (B) 1-year post-LT mortality

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Other outcomes

Some outcomes could not be included in further meta-analysis. The sarcopenia presence is related to higher 1-year mortality (HR = 1.81, 95% CI: 1.29–2.54, p < 0.01) [29]. When considering sarcopenia as a continuous variable, a 1-unit increase of the indicator for sarcopenia is associated with lower 1-year cirrhosis incidence (OR = 0.95, 95% CI: 0.93–0.97, p = 0.028) [23], but is not significantly related to 28-day mortality (HR = 1.008, 95% CI: 0.977–1.039, p = 0.630) [26].

Publication bias and sensitivity analysis

Considering the limited number of included articles reporting the related outcomes, we simply calculated the publication bias for 90-day mortality. Egger’s test indicated a significant publication bias (p = 0.021), while Begg’s test didn’t (p = 0.296) (Fig. 5A, B). Then, we performed sensitivity analysis by sequentially omitting each study. After removing each study, Li et al. was observed to be potential a source of heterogeneity (Fig. 6).

Fig. 5
figure 5

Publication bias test based on (A) Egger’s test; (B) Begg’s test

Full size image
Fig. 6
figure 6

Sensitivity analysis for 90-day mortality

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Subgroup analysis and meta-regression

To find the potential source of heterogeneity in 90-day mortality, subgroup analysis, and meta-regression were performed based on different grouping factors. Since the country, study design, ACLF criteria, and etiology were the same in the three included studies, we only completed subgroup analysis according to sarcopenia definition. The different sarcopenia definitions can not explain the heterogeneity with a P-value of 0.425 in meta-regression (Table S2).

Discussion

To our knowledge, this is the first systematic review and meta-analysis to report the prevalence and prognostic value of sarcopenia in ACLF. First, more than half of ACLF patients may suffer from sarcopenia. Second, the presence of sarcopenia is significantly related to a worse prognosis. In addition, continuous variables used to evaluate sarcopenia are also potential prognostic indicators.

Our results were consistent with previous studies focusing on the prognostic significance of sarcopenia in other liver diseases. In CLD patients with different etiologies, sarcopenia is confirmed to be an unfavorable prognosis indicator [11, 33]. An updated meta-analysis including 39 studies reported that the overall prevalence of sarcopenia was 44% (95% CI: 38-50%) in cirrhosis patients, and the presence of sarcopenia (any definition) was an independent predictor of mortality with a HR of 2.07 (95% CI 1.81–2.36), which is similar to previous publications [13, 34]. Then, in the clinical settings of liver transplantation, sarcopenia is associated with higher mortality in both post-LT patients and patients on the waiting list [35, 36]. These findings indicate that sarcopenia is an attractive marker in the population at high risk of ACLF, the sarcopenia monitoring and early intervention may slow disease progression and improve the long-term prognosis [37]. Notably, all these results were stable when considering subgroup analysis based on different etiologies, which further highlighted the universal clinical significance of sarcopenia in the liver disease spectrum. Additionally, liver failure was identified as the primary cause of short-term death in ACLF, whereas the proportion of deaths attributable to septic shock resulting from infection increased in the long term [38, 39]. In our analysis, sarcopenia is related to both worse short- and long-term outcomes, which could be supported by the effect of sarcopenia in these complications [40,41,42]. Particularly, Li et al. reported non-significant results, which may be attributed to the small sample size, potentially introducing heterogeneity. However, this study offers an intriguing perspective that ACLF represents an acute decompensation of liver function in patients with CLDs, typically occurring within 4 weeks. The study suggests that skeletal muscle mass may remain relatively stable during this short period, and the baseline L3-SMI levels are primarily influenced by the CLDs, which means the impact on short-term mortality in ACLF patients is more closely linked to the underlying CLDs than to the L3-SMI [26]. This controversy needs further investigations. Furthermore, the association between sarcopenia and post-LT-related outcomes, such as post-LT survival and graft survival rate, are important in ACLF conditions, since they can provide insights for post-LT recovery and long-term management for ACLF patients [43].

The interaction between ACLF and sarcopenia has been explored in multiple dimensions. First, portal systemic complications and impaired liver function often result in reduced oral intake, culminating in malnutrition, which is common in CLDs [29]. Second, although a large portion of ACLF cases evolve from cirrhosis, the central pathogenesis in ACLF diverges from cirrhosis in that ACLF is driven by systemic inflammation, which also plays a key role in sarcopenia [2, 44]. The intense systemic inflammation coupled with hyperammonemia incites oxidative stress (OS), fostering a prolonged state of increased catabolic activity. This metabolic imbalance leads to insulin resistance, heightened protein catabolism, and a chronic negative nitrogen balance, all of which increase the susceptibility to muscle atrophy. Then, individuals with ACLF usually exhibit enhanced glycolysis, mitochondrial dysfunction, decreased ATP production, impaired muscle regeneration, and a more accelerated rate of muscle breakdown [29, 45, 46]. Furthermore, glucocorticoid administration due to hepatitis or cirrhosis presents another risk factor for sarcopenia due to the potential of glucocorticoids to induce OS in muscle tissue by activating nuclear transcription factors in the forkhead box O family and exacerbating muscle atrophy [47]. Patients with sarcopenia are at an elevated risk of developing new infections and hepatic encephalopathy due to weakened immune systems, further intensifies ACLF progression, which leads to a vicious cycle [48]. Some potential targets have been reported to be pathogenic factors, such as myostatin, and some proinflammatory cytokines (TNF-α, IL-6, IL-1, and IFN-γ), but their precise effects are still underexploring [6]. In essence, the association between ACLF and sarcopenia is complex, and it is crucial to highlight that the pathogenesis and metabolic alterations in ACLF are distinct from those in cirrhosis. Considering different etiologies of ACLF (e.g., virus, alcohol, autoimmune-related, and metabolic dysfunction), the direction and statistical significance will not change, which was confirmed by some meta-analyses [13, 34]. However, the fundamental mechanisms under different etiologies are distinct. For example, sarcopenia can be induced by a complex and multifaceted virus-host-environment interplay in viral hepatitis, sarcopenia in metabolic dysfunction-associated liver disease or non-alcoholic fatty liver disease is mainly related to metabolic imbalance, while sarcopenia in autoimmune liver disease is relatively underexplored [33, 49,50,51]. Totally speaking, subgroup analyses based on different etiologies are crucial in the future.

The measurement indicators for sarcopenia are various. The criteria based on computed tomography (CT)-evaluated L3-SMI proposed by Carey et al. and Japan Society of Hepatology guideline were the most commonly used [30, 31]. Artru et al. validated the efficacy of PMI and TPMT/height in post-LT ACLF patients and found that using psoas cut-offs underestimates the patients under higher mortality risk [22]. Although the criteria for sarcopenia differ, the impact of sarcopenia on adverse outcomes in ACLF patients has been consistently recognized [26]. In ACLF settings, it is crucial to evaluate factors associated with mortality not only at the time of admission to the intensive care unit (ICU) but also continuously throughout the ICU stay [27]. While frailty is well-defined, its accurate assessment can be challenging in ACLF patients because of the use of sedation or mechanical ventilation or the presence of severe hepatic encephalopathy [27, 52]. Therefore, CT-evaluated sarcopenia emerges a promising tool since it is regularly performed in routine examination for intra-abdominal complications and/or hepatocellular carcinoma. According to the latest EASL guidelines, the assessment of sarcopenia is the strongly recommended tool in the ACLF population [52]. Furthermore, compared to specially defined cut-offs for sarcopenia, using the continuous variables can reflect the dynamic changes, and their values are still unclear. A combined approach incorporating both dichotomized variables and continuous variables to comprehensively measure sarcopenia is potential.

Current evidence has demonstrated that sarcopenia is significantly associated with worse clinical outcomes in acute-on-chronic liver failure (ACLF), although the number of studies remains limited. However, several key future perspectives should be considered. First, early interventions for sarcopenia, including physical exercise and pharmacological therapy, are crucial for patients with ACLF or CLDs [37]. Second, dynamic monitoring of sarcopenia during ACLF progression could provide valuable insights into muscle mass and function, but such monitoring tools still require development and validation. Third, since nutritional status and frailty indicators also play important roles in ACLF, a comprehensive assessment framework integrating sarcopenia, nutritional status, and frailty evaluation holds significant promise. Additionally, the current variability in diagnostic cut-off values for sarcopenia underscores the need for standardized criteria. Finally, all these findings require validation through large-scale prospective cohort studies in the future.

There are some strengths in our study. First, different cohorts in a single study were separately extracted to maximize the total population and enhance the stability of the conclusion. Second, we analyzed sarcopenia by using both cut-offs and continuous variables to reflect the presence of sarcopenia and the dynamic alterations of muscle assessment. Additionally, this study further fills the gap of sarcopenia in ACLF and further deepens the understanding of sarcopenia in various liver diseases.

Some limitations should be acknowledged. First, only nine studies were included in the analysis, and studies available for different outcomes were relatively few. Second, due to the limited number of included literature, the heterogeneity and publication bias cannot be fully investigated. Third, the optimal cut-off for sarcopenia is still not reached.

Conclusion

This systematic review and meta-analysis present that sarcopenia widely exists in ACLF patients, and it is associated with both unfavorable short- and long-term prognoses. CT-evaluated sarcopenia is a capable and accessible indicator for ACLF prognosis measurement. More well-designed and high-quality studies are necessary to further confirm these findings in the future.

Data availability

The datasets supporting the conclusions of this article are included in the article.

Abbreviations

ACLF :

Acute-on-chronic liver failure

CLD:

Chronic liver disease

LT:

Liver transplantation

MELD:

Model for End-stage Liver Disease

MOOSE:

Meta-analysis of Observational Studies in Epidemiology

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyzes

OR:

Odds ratio

HR:

Hazard ratio

RR:

Risk ratio

RoB 2:

Risk of Bias Tool-2

NOS:

Newcastle-Ottawa Quality Assessment Scale

CI:

Confidence interval

SMI:

Skeletal muscle index

CT:

Computed tomography (CT)

PMI:

Psoas muscle index (PMI)

TPMT/height:

Transversal right psoas muscle thickness at the umbilical level/height

ICU:

Intensive care unit

References

  1. Kulkarni AV, Sarin SK. Acute-on-chronic liver failure - steps towards harmonization of the definition! J Hepatol. 2024;81:360–6.

    Article  CAS  PubMed  Google Scholar 

  2. Br VK, Sarin SK. Acute-on-chronic liver failure: terminology, mechanisms and management. Clin Mol Hepatol. 2023;29:670–89.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hernaez R, Kramer JR, Liu Y, Tansel A, Natarajan Y, Hussain KB, et al. Prevalence and short-term mortality of acute-on-chronic liver failure: A National cohort study from the USA. J Hepatol. 2019;70:639–47.

    Article  PubMed  Google Scholar 

  4. Agostini C, Buccianti S, Risaliti M, Fortuna L, Tirloni L, Tucci R, et al. Complications in Post-Liver transplant patients. J Clin Med. 2023;12:6173.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mezzano G, Juanola A, Cardenas A, Mezey E, Hamilton JP, Pose E, et al. Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis. Gut. 2022;71:148–55.

    Article  CAS  PubMed  Google Scholar 

  6. Peng H, Zhang Q, Luo L, Lei S, Xiong T, Long L, et al. A prognostic model of acute-on-chronic liver failure based on sarcopenia. Hepatol Int. 2022;16:964–72.

    Article  PubMed  Google Scholar 

  7. Chang Y, Liu Q-Y, Zhang Q, Rong Y-M, Lu C-Z, Li H. Role of nutritional status and nutritional support in outcome of hepatitis B virus-associated acute-on-chronic liver failure. World J Gastroenterol. 2020;26:4288–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sayer AA, Cooper R, Arai H, Cawthon PM, Ntsama Essomba M-J, Fielding RA, et al. Sarcopenia Nat Rev Dis Primers. 2024;10:68.

    Article  PubMed  Google Scholar 

  9. Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 Suppl):S990–1.

    Article  Google Scholar 

  10. Sayer AA, Cruz-Jentoft A. Sarcopenia definition, diagnosis and treatment: consensus is growing. Age Ageing. 2022;51:afac220.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016;65:1232–44.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hong HC, Hwang SY, Choi HY, Yoo HJ, Seo JA, Kim SG, et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean sarcopenic obesity study. Hepatology. 2014;59:1772–8.

    Article  CAS  PubMed  Google Scholar 

  13. Dajti E, Rodrigues SG, Perazza F, Colecchia L, Marasco G, Renzulli M, et al. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Marasco G, Serenari M, Renzulli M, Alemanni LV, Rossini B, Pettinari I, et al. Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments. J Gastroenterol. 2020;55:927–43.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Dhaliwal A, Armstrong MJ. Sarcopenia in cirrhosis: A practical overview. Clin Med (Lond). 2020;20:489–92.

    Article  PubMed  Google Scholar 

  16. Brooke BS, Schwartz TA, Pawlik TM. MOOSE reporting guidelines for Meta-analyses of observational studies. JAMA Surg. 2021;156:787–8.

    Article  PubMed  Google Scholar 

  17. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wojtyniak J-G, Britz H, Selzer D, Schwab M, Lehr T. CPT Pharmacometrics Syst Pharmacol. 2020;9:322–31. Data Digitizing: Accurate and Precise Data Extraction for Quantitative Systems Pharmacology and Physiologically-Based Pharmacokinetic Modeling.

  19. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

    Article  PubMed  Google Scholar 

  20. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.

    Article  PubMed  Google Scholar 

  21. Tufanaru C, Munn Z, Stephenson M, Aromataris E. Fixed or random effects meta-analysis? Common methodological issues in systematic reviews of effectiveness. Int J Evid Based Healthc. 2015;13:196–207.

    Article  PubMed  Google Scholar 

  22. Artru F, le Goffic C, Pageaux G-P, Saliba F, Louvet A. Sarcopenia should be evaluated in patients with acute-on-chronic liver failure and candidates for liver transplantation. J Hepatol. 2022;76:983–5.

    Article  PubMed  Google Scholar 

  23. Bai J, Xu M, Peng F, Gong J, Zhao J, Song X, et al. Skeletal muscle mass index as a predictor of long-term cirrhosis onset in young non-cirrhotic males with acute-on-chronic liver failure. Front Nutr. 2022;9:1071373.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Geng N, Kong M, Zhang J, Chen H, Xu M, Song W, et al. Association of myosteatosis with short-term outcomes in patients with acute-on-chronic liver failure. Sci Rep. 2024;14:13609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Khan S, Benjamin J, Maiwall R, Tripathi H, Kapoor PB, Shasthry V, et al. Sarcopenia is the independent predictor of mortality in critically ill patients with cirrhosis. J Clin Transl Res. 2022;8:200–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Li T, Xu M, Kong M, Song W, Duan Z, Chen Y. Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure. Sci Rep. 2021;11:12593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Del Mangana T, Sacleux S-C, Vionnet J, Ichaï P, Denys A, Schneider A, et al. Body composition and short-term mortality in patients critically ill with acute-on-chronic liver failure. JHEP Rep. 2023;5:100758.

    Article  Google Scholar 

  28. Perdiguero GG, Spina JC, Martínez J, Savluk L, Saidman J, Bonifacio M, et al. Enhancing ACLF prediction by integrating sarcopenia assessment and frailty in liver transplant candidates on the waiting list. JHEP Rep. 2024;6:100985.

    Article  PubMed  Google Scholar 

  29. Zeng F, Jiang W, Chang X, Yang F, Luo X, Liu R, et al. Sarcopenia is associated with short- and long-term mortality in patients with acute-on-chronic liver failure. J Cachexia Sarcopenia Muscle. 2024;15:1473–82.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S. Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res. 2016;46:951–63.

  31. Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl. 2017;23:625–33.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kong M, Geng N, Zhou Y, Lin N, Song W, Xu M, et al. Defining reference values for low skeletal muscle index at the L3 vertebra level based on computed tomography in healthy adults: A multicentre study. Clin Nutr. 2022;41:396–404.

    Article  PubMed  Google Scholar 

  33. Coelho MPP, De Castro PASV, De Vries TP, Colosimo EA, Bezerra JMT, Rocha GA, et al. Sarcopenia in chronic viral hepatitis: from concept to clinical relevance. World J Hepatol. 2023;15:649–65.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tantai X, Liu Y, Yeo YH, Praktiknjo M, Mauro E, Hamaguchi Y, et al. Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis. J Hepatol. 2022;76:588–99.

    Article  PubMed  Google Scholar 

  35. van Vugt JLA, Levolger S, de Bruin RWF, van Rosmalen J, Metselaar HJ, IJzermans JNM. 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 Transpl. 2016;16:2277–92.

    Article  Google Scholar 

  36. Jiang M-J, Wu M-C, Duan Z-H, Wu J, Xu X-T, Li J, et al. Prevalence and clinical impact of sarcopenia in liver transplant recipients: A meta-analysis. World J Gastroenterol. 2024;30:956–68.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kim Y. Emerging treatment options for sarcopenia in chronic liver disease. Life (Basel). 2021;11:250.

    CAS  PubMed  Google Scholar 

  38. Premkumar M, Saxena P, Rangegowda D, Baweja S, Mirza R, Jain P, et al. Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute-on-chronic liver failure: an observational cohort study. Liver Int. 2019;39:694–704.

    Article  CAS  PubMed  Google Scholar 

  39. Fernández J, Acevedo J, Wiest R, Gustot T, Amoros A, Deulofeu C, et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut. 2018;67:1870–80.

    Article  PubMed  Google Scholar 

  40. Kizilarslanoglu MC, Kuyumcu ME, Yesil Y, Halil M. Sarcopenia in critically ill patients. J Anesth. 2016;30:884–90.

    Article  PubMed  Google Scholar 

  41. Cox MC, Booth M, Ghita G, Wang Z, Gardner A, Hawkins RB, et al. The impact of sarcopenia and acute muscle mass loss on long-term outcomes in critically ill patients with intra-abdominal sepsis. J Cachexia Sarcopenia Muscle. 2021;12:1203–13.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Krell RW, Kaul DR, Martin AR, Englesbe MJ, Sonnenday CJ, Cai S, et al. Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation. Liver Transpl. 2013;19:1396–402.

    Article  PubMed  Google Scholar 

  43. Bhanji RA, Takahashi N, Moynagh MR, Narayanan P, Angirekula M, Mara KC, et al. The evolution and impact of sarcopenia pre- and post-liver transplantation. Aliment Pharmacol Ther. 2019;49:807–13.

    Article  PubMed  Google Scholar 

  44. Bano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B, et al. Inflammation and sarcopenia: A systematic review and meta-analysis. Maturitas. 2017;96:10–5.

    Article  PubMed  Google Scholar 

  45. Zhang D, Shi C, Wang Y, Guo J, Gong Z. Metabolic dysregulation and metabolite imbalances in Acute-on-chronic liver failure: impact on immune status. J Clin Transl Hepatol. 2024;12:865–77.

    PubMed  PubMed Central  Google Scholar 

  46. Moreau R, Clària J, Aguilar F, Fenaille F, Lozano JJ, Junot C, et al. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF. J Hepatol. 2020;72:688–701.

    Article  CAS  PubMed  Google Scholar 

  47. Sato AY, Richardson D, Cregor M, Davis HM, Au ED, McAndrews K, et al. Glucocorticoids induce bone and muscle atrophy by Tissue-Specific mechanisms upstream of E3 ubiquitin ligases. Endocrinology. 2017;158:664–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Lucidi C, Lattanzi B, Di Gregorio V, Incicco S, D’Ambrosio D, Venditti M, et al. A low muscle mass increases mortality in compensated cirrhotic patients with sepsis. Liver Int. 2018;38:851–7.

    Article  PubMed  Google Scholar 

  49. Iwaki M, Kobayashi T, Nogami A, Saito S, Nakajima A, Yoneda M. Impact of sarcopenia on Non-Alcoholic fatty liver disease. Nutrients. 2023;15:891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. An HJ, Tizaoui K, Terrazzino S, Cargnin S, Lee KH, Nam SW, et al. Sarcopenia in autoimmune and rheumatic diseases: A comprehensive review. IJMS. 2020;21:5678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Crişan D, Avram L, Morariu-Barb A, Grapa C, Hirişcau I, Crăciun R, et al. Sarcopenia in MASLD—Eat to beat steatosis, move to prove strength. Nutrients. 2025;17:178.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Moreau R, Tonon M, Krag A, Angeli P, Berenguer M, Berzigotti A, et al. EASL clinical practice guidelines on acute-on-chronic liver failure. J Hepatol. 2023;79:461–91.

    Article  Google Scholar 

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Acknowledgements

We thank all authors of studies included in meta-analysis.

Funding

This study is funded by the Science and Technology Support Program of Sichuan Province (2024YFFK0275).

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Author notes

  1. Sike He and Chang-Hai Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China

    Sike He, Yuan Wang, Ziqi Li, Zhenhua Liu, Hao Zeng & Guangxi Sun

  2. Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China

    Chang-Hai Liu

  3. Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China

    Chang-Hai Liu

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  1. Sike He
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Contributions

Concept and design：Sike He and Chang-Hai Liu; Writing of the manuscript: Sike He, and Yuan Wang; Figure and table preparation: Yuan Wang and Ziqi Li; Final review and editing: Chang-Hai Liu, Zhenhua Liu, Hao Zeng, and Guangxi Sun.

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Correspondence to Sike He, Hao Zeng or Guangxi Sun.

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Supplementary Material 1: Table S1. Variables included in the multivariate model in eligible studies. Table S2. Subgroup analysis for the influence of sarcopenia on 90-day mortality

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He, S., Liu, CH., Wang, Y. et al. The prognostic value of sarcopenia in acute-on-chronic liver failure: a systematic review and meta-analysis. BMC Gastroenterol 25, 300 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12876-025-03926-8

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Keywords

BMC Gastroenterology

ISSN: 1471-230X

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