CT-defined sarcopenia as a predictive factor in patients undergoing portal vein embolization: a systematic review and meta-analysis

Introduction

Body composition can be assessed by cross-sectional imaging on the L3 level calculating the skeletal muscle mass of one axial slice (1-5). In most studies, the low-skeletal muscle mass defined by computed tomography (CT) is used as a surrogate parameter of sarcopenia (3,5). Sarcopenia defined by low-skeletal muscle mass on CT images was an important prognostic and predictive factor in different liver tumors undergoing different treatments in curative as well as palliative setting (6-10).

One of the major complications of major liver surgery is postoperative liver failure, which is caused by an insufficient volume of the future liver remnant (FLR) after the resection (11-16). The reported postoperative 90-day mortality after liver resection is high with 7.4% for major resection and 11.4% for extended resections (17,18). One important aspect is that clinically assessed frailty has a meaningful impact on the postoperative mortality with a reported odds ratio of 2.9 (18,19).

One clinically important interventional procedure to improve liver growth before major liver surgery is portal vein embolization (PVE), which is an effective procedure to reduce postoperative complications and improve the patient’s condition for a subsequent liver resection (20-23).

In addition, other patient characteristics can have an influence on the outcome of the liver growth after PVE (21). Important aspects for the outcome of PVE includes procedure related features, such as type of embolization agent and technique and the additional embolization of segment 4 (15,20,24,25). In addition, first exploratory results have demonstrated that CT-defined sarcopenia has a relevant influence on the hepatic regeneration capacities and the FLR in patients undergoing PVE (26). Different methods were described in the literature to assess sarcopenia by CT images with different used threshold values (1-5).

In a pathophysiological point of view, it is known that in particular circumstances, muscle cells are the main source of interleukine-6 production, which has an important role in liver regeneration (27). Additionally, it is known that cachexia as the inflammatory muscle wasting syndrome has a relevant impact on liver regeneration via the inflammasome pathway (28).

However, to the best of our knowledge these promising results of the impact of CT-defined sarcopenia on PVE treatment outcome were not assessed in a systematic review and meta-analysis before. Beyond that, the pathophysiological implications of the systemic cross-talk between skeletal muscles and liver generation well deserve further investigation. Due to the heterogeneity of the CT-sarcopenia literature with different methodology, different primary tumor and PVE technique, these can best be investigated with a meta-analysis approach of real-world data.

Therefore, the aim of this systematic review and meta-analysis was to investigate the impact of the CT-defined sarcopenia on the outcome of PVE. We present this article in accordance with the PRISMA reporting checklist (29) (available at https://tgh.amegroups.com/article/view/10.21037/tgh-2026-0024/rc).

Methods

This meta-analysis was registered in the PROSPERO registry (CRD420251128894).

The primary endpoints of the systematic review were the increase or the volume or the growth rate per week of mean FLR in % between the groups stratified by sarcopenia.

In addition, the correlation coefficient between liver growth rate and the skeletal muscle index (SMI) extracted as a secondary endpoint.

Postoperative liver failure, postoperative 90-day mortality and resection rate stratified to sarcopenia status were further secondary endpoints of the study.

Inclusion criteria

Studies (or subsets of studies) were included if they met the following criteria: (I) patients undergoing PVE; (II) sarcopenia defined by CT; (III) reported mean difference (MD) for the liver growth rate after PVE.

Exclusion criteria included article type of (I) systematic review, (II) case report, and with (III) non-English language.

Data extraction

Data extraction was first performed by one experienced author in systematic reviews (*H.J.M.) followed by an independent evaluation of extractions for correctness by a senior author (*A.S.). For each study the following features were extracted, details regarding study design, year of publication, country of origin, patient number, patient age, tumor diagnosis, sarcopenia measurement with Hounsfield unit threshold, segmentation software, sarcopenia definition, postoperative liver failure, postoperative mortality, postoperative resection rate. Regarding the PVE, the embolized side and embolization material was extracted. For the outcome measurements, the future liver remnant volume (FLRV), the FLRV increase and the growth rate per week were extracted from the studies.

Search strategy

The MEDLINE library database was searched for articles on the effect of sarcopenia/low skeletal muscle mass on PVE up to February 2026. The literature search is summarized in Figure 1.

Figure 1 PRISMA flow chart provides an overview of the paper acquisition. Overall, seven studies with 599 patients were suitable for the analysis.

The following search terms were used: “portal vein embolization” AND “sarcopenia”. A secondary search with different search terms did not identify more suitable articles.

The time frame was set from January 2020 to February 2026.

After review, a total of seven studies were eligible for analysis and included in the present study (26,30-35).

Quality-assessment

The study quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS) (http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm) (36). The quality assessment of the studies was performed by two authors independently to each other (*H.J.M. and S.Z.). The scale includes features regarding the selection of patients, the comparability of the investigated study cohorts and the potential bias to outcome assessment. The scale ranges from 0–9 and a study with a value above 6 can be considered to be of high quality.

Statistical analysis

The present meta-analysis was performed using RevMan 5.4 (2020; Cochrane Collaboration, Copenhagen, Denmark). The heterogeneity of the different results was calculated by means of the inconsistency index I² (37,38). As previously stated, values in the range of 30% to 60% can be interpreted as modest, while values less than 15% to 25% may be considered “low”, and greater than 75% to 80% “high” (39). DerSimonian and Laird random-effect models with inverse-variance weights were performed without any further correction (40). Due to the expected heterogeneity across the included studies, this model can be considered more appropriate compared to fixed-effect model. Whenever interquartile range was mentioned instead of mean, the following formula was applied: (Q3 − Q1)/1,349 (41). Reported range values were transferred to standard deviation by a division of 4 (42). Pearson’s correlation coefficients were transferred to Spearman’s correlation coefficient (43). Due to the inclusion of less than 10 studies, a test for publication bias was not performed, as suggested by the Cochrane handbook (43).

Results

Table 1 gives an overview of the included studies. All studies had a retrospective design. One study was a multicenter observational cohort study (33), whereas the other studies were from a single center.

Three studies were published from Asia (42.9%), three studies from Europe (42.9%) and one study from North America (14.2%).

Bias assessment

The overall risk of bias can be considered as low to moderate due to the retrospective study designs of the included studies. However, the sarcopenic and non-sarcopenic patients were treated in a similar fashion throughout the included studies that a controlled comparison can be assumed.

The NOS values are moderate with 7 throughout the studies except one study (Table 2).

Overview of the included studies

The included studies comprised overall 599 patients with a mean age of 62.9 years of all studies. The patient number per study ranged from 21 to 306 patients per study with a mean patient number of 86.

The patients had the following tumors hepatocellular carcinoma in 70 cases (11.7%), colorectal liver metastasis in 325 cases (54.2%), intrahepatic cholangiocellular carcinoma in 45 cases (7.5%), perihilar cholangiocellular carcinoma in 96 cases (16.0%), gallbladder carcinoma in 42 cases (7.1%) and in 21 cases (3.5%) tumors not otherwise specified.

Different embolization techniques were utilized throughout the studies (Table S1). In most cases, right sided embolization was performed. Only in a very small number of patients, left sided embolization was performed (n=3 patients) (33).

Regarding sarcopenia assessment, all studies used the SMI on L3 level measuring the muscle area of the abdominal wall, psoas and lumbar muscles. All studies used a semiautomatically manner to segment the skeletal muscle area. Regarding the software to measure the skeletal muscle area, three studies used the Osirix package, two studies used 3D slicer and two studies did not report the name of the software used.

Most studies used the Hounsfield-threshold of −30 to 150 to define the skeletal muscle areas, but three studies did not report the threshold values (30,31,35). The measurement can be considered as the current scientific standard.

Different cut-off values were used to define sarcopenia. Four studies used the proposed cut-offs by Martin et al. [for females, SMI 41 cm²/m²; for males, SMI 43 cm²/m² with a body mass index (BMI) <25 kg/m²] and SMI 53 cm²/m² with a BMI >25 kg/m² (26,31-33), one study used the cut-offs 42 cm²/m² for males and 38 cm²/m² for females according to the Japan Society of Hepatology guidelines (30) and one study used for males 47.1 cm²/m² and females 36.6 cm²/m² (34). One study did not dichotomize the patient cohort according to one threshold value (35).

Of the included 599 patients, 353 were classified as sarcopenic (58.9%), 204 were non-sarcopenic (34.1%) and 42 were not classified (7.0%).

Meta-analysis

The effect of low skeletal muscle mass/sarcopenia on the outcome of PVE was measured in different outcome parameters.

For the effect of the FLRV, three studies including 171 patients were included in the analysis (Figure 2A). The pooled MD between the sarcopenic and non-sarcopenic group was 2.70% {[95% confidence interval (CI): 0.31–5.09%], Z=2.22, P=0.03, Tau²=0, Chi²=0.21, df =2 (P=0.90), I²=0} favoring the patients with non-sarcopenia.

Figure 2 Forest plots of the effect of CT-defined sarcopenia on therapy outcome. (A) Forest plots of the effect of CT-defined sarcopenia on the outcome effect of the FLRV. The pooled mean difference between the sarcopenic and non-sarcopenic group was 2.70% [(95% CI: 0.31–5.09%), P=0.03] favoring the patients with non-sarcopenia. (B) Forest plots of the effect of CT-defined sarcopenia of the FLRV increase in %. The pooled mean difference between the sarcopenic and non-sarcopenic group was 10.87% [(95% CI: 3.45–18.30%), P=0.004] favoring the patients with non-sarcopenia. (C) Forest plots of the effect of CT-defined sarcopenia for the FLRV growth rate per week. The pooled mean difference between the sarcopenic and non-sarcopenic group was 2.46% [(95% CI: 0.74–4.17%), P=0.005] favoring the patients with non-sarcopenia. CI, confidence interval; CT, computed tomography; FLRV, future liver remnant volume; IV, inverse variance; SD, standard deviation.

For the effect of the FLRV increase in %, four studies including 453 patients were included in the analysis (Figure 2B). The pooled MD between the sarcopenic and non-sarcopenic group was 10.87% [(95% CI: 3.45–18.30%), Z=2.87, P=0.004, Tau²=16.78, Chi²=4.21, df =3 (P=0.24), I²=29%] favoring the patients with non-sarcopenia.

For the effect of the FLRV growth rate per week, four studies including 496 were included in the analysis (Figure 2C). The pooled MD between the sarcopenic and non-sarcopenic group was 2.46% [(95% CI: 0.74–4.17%), Z=2.81, P=0.005, Tau²=2.41, Chi²=24.86, df =3 (P<0.0001), I²=88%] favoring the patients with non-sarcopenia.

Correlation analysis between SMI and liver growth rate

In a subanalysis of four studies with overall 447 patients a correlation analysis between SMI and the liver growth rate was performed. This analysis included all suitable patients sarcopenic and non-sarcopenic. The pooled correlation coefficient between the SMI and the growth rate was 0.40 (95% CI: 0.17–0.63), Z=3.37, P<0.001, Tau²=0.04, Chi²=17.17, df =3 (P<0.001), I²=83% (Figure 3).

Figure 3 Forest plots of the correlation analysis between skeletal muscle index and the liver growth rate. The pooled correlation coefficient was 0.40 (95% CI: 0.17–0.63), P<0.001. CI, confidence interval; IV, inverse variance; SE, standard error.

Resection rate

In three studies with overall 432 patients the possible resection rate was reported according to the sarcopenia status (26,31,33). In the sarcopenia group, 190 of 282 patients could undergo resection, whereas in the non-sarcopenia group, 119 of 150 patients could undergo resection. There was no statistically significant difference in resection rate between groups. The pooled odds ratio was 0.73 [95% CI: 0.23–2.30, Z=0.54, P=0.59, Tau²=0.76, Chi²=7.89, df =2 (P=0.02), I²=75%] (Figure 4A).

Figure 4 Forest plots of the effect of CT-defined sarcopenia on postoperative outcomes. (A) Forest plots of the post-interventional resection rate. The pooled odds ratio was 0.73 (95% CI: 0.23–2.30, P=0.49). There was no statistically significant difference in post-interventional resection rate between groups. (B) Forest plots of the 90-day mortality rate. The pooled odds ratio was 0.91 (95% CI: 0.38–2.18, P=0.84). There was no statistically significant difference in postoperative mortality between groups. (C) Forest plots of the postoperative liver failure. The pooled odds ratio was 0.58 (95% CI: 0.33–1.03, P=0.06). There was no statistically significant difference in postoperative liver failure between groups. CI, confidence interval; CT, computed tomography; M-H, Mantel-Haenszel method.

Postoperative 90-day mortality

Three studies reported the postoperative 90-day mortality stratified by sarcopenia status with overall 432 patients (26,31,33). In the sarcopenia group 15 died of 282 (5.3%) and in the non-sarcopenia group 9 of 150 patients died (6.0%). There was no statistically significant difference in postoperative mortality between groups. The pooled odds ratio was 0.91 [95% CI: 0.38–2.18, Z=0.21, P=0.84, Tau²=0, Chi²=0.11, df =2 (P=0.95), I²=0] (Figure 4B).

Postoperative liver failure

Three studies reported the postoperative liver failure stratified by sarcopenia status with overall 432 patients (26,31,33). In the sarcopenia group 31 of 282 patients (10.9%) showed signs of liver failure and 31 of 150 patients (20.7%) in the non-sarcopenia group. There was no statistically significant difference in postoperative liver failure between groups. The pooled odds ratio was 0.58 [95% CI: 0.33–1.03, Z=1.87, P=0.06, Tau²=0, Chi²=0.79, df =2 (P=0.67), I²=0] (Figure 4C).

Postoperative complication rate according to Clavien-Dindo classification

Only one study with 306 patients reported the complication rate according to the Clavien-Dindo classification (33). In the sarcopenia group 39 of 194 patients had a major complication defined by Clavien-Dindo ≥ IIIA (31%) and 32 of 112 in the non-sarcopenia had a major complication (33%). There was no statistical analysis possible for postoperative complication rate.

Discussion

The present analysis investigated the impact of CT-defined sarcopenia on the FLRV, increase in % and growth rate per week after PVE. The key finding of the present meta-analysis was that patients with CT-defined sarcopenia have a lower liver growth rate compared to non-sarcopenic patents. This was demonstrated for the first time based on published results of the last years. The present study could now show that especially the growth rate is affected by sarcopenia with the highest statistical significance compared to volume growth.

The identified heterogeneity of the present studies was moderate in the overall analysis but was high in the subgroup analyses, which needs to be considered when interpreting the current results. Moreover, the main results of the discrimination analysis and the correlation analysis were only modest indicating only a small impact for clinical work up of these patients. Beyond that, the clinically relevant outcomes did not reach statistical significance for 90-day mortality, resection rate, and postoperative liver failure. Better stratified patient samples and better adjustment for confounders are needed to demonstrate also significant results for these clinically relevant outcomes.

The main rationale for the effect of sarcopenia on the outcome of PVE is that sarcopenia and cachexia have a systemic and endocrine effect for different organ systems including the liver and therefore may impair the regeneration function of the liver parenchyma (1-5).

The present analysis can harmonize the previously published data to demonstrate a significant correlation between the SMI and the liver growth rate with a moderate positive association. Moreover, it can clearly demonstrate that sarcopenic patients have a smaller liver growth rate per week as non-sarcopenic patients.

However, not all included studies could demonstrate a statistically significant difference between both groups in every investigated future liver parameter, as shown in the study by Araki et al. or Denbo et al. for FLRV (30,32).

PVE has a key role for surgical treatment planning to reduce the frequency of postoperative complications and mortality (21,22). There is plethora of data emphasizing the importance of the choice of embolic agent of PVE, with a superiority of NBCA over PVA plus coils (24,25). Moreover, it seems beneficial to embolize segment IV with a higher hypertrophy rate (22,25). These heterogeneities of the FLR growth should also be considered, when discussing the current results based on different studies with different techniques.

The present analysis is in line with a previous meta-analysis on the impact of CT-defined sarcopenia on the liver growth rate after surgically liver partition and portal vein ligation (44).

A more liberal approach to perform preoperative PVE was indented to decrease liver failure and mortality rates (45-47). In one interesting study liver function measured by LiMAx, a functional test based on the metabolism of the non-radioactive diagnostic agent 13C-methacetin, was not affected by sarcopenia, which could indicate a limited affection of the liver by low-skeletal muscle mass (46).

It seems that the morphological assessment and the functional assessment by the LiMAx reflect different aspects of the liver state. The combination of CT-defined sarcopenia and the functional LiMAx is warranted in future research trials to better characterize the patients undergoing PVE and major liver surgery.

However, the skeletal muscle mass and sarcopenia assessment has a meaningful impact on the liver by the mediation of myokines, which was investigated in patients with liver cirrhosis (48). In addition, liver regeneration can be lower in sarcopenic patients via the mediation of interleukin-6 (27). This further leads to the importance to better stratify the patient cohorts according to the presence of liver cirrhosis, which could have a substantial influence on the association between sarcopenia and future liver growth. However, this could not be adjusted for in the present analysis.

There is some heterogeneity of sarcopenia measurement based on CT images. Some authors only measured the psoas muscle area as a surrogate parameter, but the recommended standard is the measurement of all muscles on L3 level (5). This was performed in every included study in the analysis to ensure a high scientific standard. A possible small confounder could be the different SMI threshold values to define sarcopenia used between the included studies. It is still a debate, which SMI threshold value should be used to define sarcopenia (5).

One key aspect of the sarcopenia assessment in patients undergoing PVE is that hepatic volume has a proportional relationship to body mass and body surface area and that after hepatic resection a normal liver will regenerate to a set liver/body mass-ratio (49). It seems logical that CT-based composition assessment can even better characterize the patient than the sole body mass or body surface area. Presumably, fat areas are not as important for liver growth as the overall muscle function of the patient.

The effect of the CT-defined sarcopenia seems to be of less clinical importance indicated by the negative subgroup analysis results for resection rate and postoperative 90-day mortality in the present analysis. This need a more comprehensive investigation, why sarcopenia has a significant impact on liver growth after PVE but was not associated with the relevant clinically outcomes. It may be caused by the small sample sizes in the included studies that the relevant liver growth did not translate into the clinical outcome change. Moreover, it could be caused by the retrospective design of the included studies that some patients undergoing PVE were not accurately assessed in the cohorts.

Although the analysis did not reach statistical significance it appears that sarcopenic patients were favored for a lower resection rate. This raises the potential inclusion of selection bias that the surgeons may have been less likely to proceed to hepatectomy in frailer or sarcopenic patients after PVE. This could also have a relevant impact on the 90-day mortality after PVE accordingly to sarcopenic status of the patients. Thus, it remains still unclear, whether the postoperative mortality after resection is independent of the sarcopenia status or may be affected by treatment-selection processes during clinical routine.

This issue is important because postoperative 90-day mortality is, by definition, assessed in the subset of patients who actually underwent resection. Therefore, if sarcopenic patients with unfavorable physiology were selectively excluded from surgery, the postoperative mortality analysis may underestimate the true clinical impact of sarcopenia

A prospective evaluation of the impact of sarcopenia on clinically relevant outcomes after PVE is warranted.

Moreover, it must to be considered that the included studies did not address a clinically relevant threshold value for achieving the FLR of 20–30% stratified to the sarcopenia status. This needs to be addressed in future investigations.

One key aspect of the present analysis is that the included studies only investigated the skeletal muscle area as a surrogate for low-skeletal muscle mass. However, the muscle quality is better assessed by the skeletal muscle density, which could be better to predict the outcome of PVE. This important muscle parameters need evaluation in further investigations.

In addition, there are very promising results regarding the higher efficacy of hepatic vein deprivation, an interventional technique to embolize the portal vein and the hepatic vein of the to be resected side (50,51). However, no study investigated the effect of sarcopenia of the liver growth after this novel procedure. There is also definite need for further research in the field of the impact of sarcopenia on the outcome of interventional radiology procedures.

Moreover, it was not possible to provide subgroup analyses to address the confounding of the embolic agent used (25). Hypothetically, different embolic agents could cause different liver hypertrophy in patients with sarcopenia and without sarcopenia.

Beyond that, it remains elusive, whether left sided embolization is also clinically affected by sarcopenia status as only one study has included patients with left sided embolization with only three patients (33). Future research is needed to address this fact.

The present meta-analysis has some limitations to address. First, it is comprised of published studies, all of them with retrospective design, with heterogeneities between studies. Possible reasons are different treatment forms and embolization methods and tumor entities of the investigated patient cohorts. Moreover, the calculated volumetric outcome measures differ between the included studies. As such, in the study by Arntz et al. the FLRV were measured using the measured total liver volume (TLV) and also defined KGR based on volumetric change relative to TLV (26). In contrast, in the study by Heil et al. standardized future liver remnant (sFLR) was measured based on standardized total liver volume (sTLV) derived from a biometric formula based on body weight (33). These differences could lead to a relevant bias of the meta-analysis. Second, there is the restriction to English language with a narrowed search strategy using only one search engine. However, we believe that all relevant studies investigating this topic were assessed in the current analysis. Third, due to the small number of included studies, it was not possible to provide a test for publication bias. Another limitation is the conversion of the median values with interquartile ranges of the included studies into mean values with standard deviation, which could have an influence on the meta analytic results. Forth, it was not possible to provide subgroup analyses regarding tumor entity and embolization technique due to the information provided by the included studies. This should be investigated in ongoing trials as it could have a relevant impact on the outcome of PVE. Moreover, it was not possible to adjust for the presence of liver cirrhosis, which could have a strong impact on the associations between CT-defined sarcopenia and liver growth. Other factors of the PVE influencing the outcome including embolization material and embolization of segment IV could not be accounted for. Therefore, we could not provide a more comprehensive meta-regression analysis to further explore confounding factors. There is definite need for future studies adjusting for potential confounders. Fifth, it was not possible to extract further aspects of PVE of the included studies such as technical success rate, complication rate or time to surgery accordingly to the sarcopenia status. This was caused by the insufficient reporting of the included studies. In the similar aspect, the standardized outcome parameters such as degree of hypertrophy, kinetic growth rate are not provided by all studies and could not pooled together in a standardized manner. Further studies are needed to assess distinctive differences of patients undergoing PVE regarding complication rate and technical success.

Conclusions

CT-defined sarcopenia has an impact on the FLR in patients undergoing PVE. However, the present analysis could not demonstrate associations with postoperative complications or overall survival due to lack of information in the investigated studies. These aspects need to be further assessed in further prospective trials to demonstrate a clinical meaningful impact of CT-defined sarcopenia in clinical routine.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-2026-0024/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-2026-0024/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-2026-0024/coif). The authors have no 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/.

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