Hepatocellular carcinoma (HCC) represents a major global health concern, characterized by evolving etiological patterns and a range of treatment options. Among various prognostic factors, sarcopenia, characterized by loss of skeletal muscle mass, strength, and function, has emerged as a pivotal contributor to HCC outcomes. Focusing on liver transplantation, surgical resection, locoregional treatments, and systemic therapies, this review aims to analyze the impact of sarcopenia on HCC treatment outcomes, shedding light on an underexplored subject in the pursuit of more personalized management.

A comprehensive literature review was conducted by searching peer-reviewed articles on sarcopenia and treatment outcomes in patients with HCC from inception up to October 2023.

Sarcopenia was found to be prevalent among HCC patients, exhibiting different occurrence, possibly attributable to diverse diagnostic criteria. Notably, despite variations in studies utilizing skeletal muscle indices, sarcopenia independently correlated with lower overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) across surgical (both transplantation and resection), locoregional, and systemic therapies, including tyrosine-kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs). Moreover, a link between sarcopenia and increased rate and severity of adverse events, particularly in surgery and TKIs recipients, and larger tumor size at diagnosis was observed. While baseline sarcopenia negatively influenced treatment outcomes, alterations in muscle mass post-treatment emerged as primary determinants of reduced OS.

Sarcopenia, either present before or after HCC treatment, negatively correlates with response to it, across all etiologies and therapeutic strategies. Although only a few studies have evaluated the impact of supervised physical activity training on muscle mass and OS after HCC treatment, it is crucial to evaluate the presence of sarcopenia before treatment initiation, to better stratify patients' prognosis, thus performing a more tailored approach, and identify therapies able to restore muscle mass in HCC patients. Conversely, the impact of sarcopenia on HCC recurrence and extrahepatic spread remains inadequately explored.

The causal association of sarcopenia with the incidence risk of hepatocellular carcinoma (HCC) in the European population, and the potential mediating role of C-reactive protein (CRP), remains unclear. This study employed a bidirectional two-sample, two-step Mendelian randomization (MR) analysis to investigate the causality and identify the mediator.

Summary statistics for HCC, CRP, and sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP), were acquired from publicly available databases. We conducted bidirectional MR and Steiger tests of directionality to check the presence of reverse causality. Additionally, a two-step MR analysis was used to assess the mediating effect of CRP in the causality between sarcopenia and HCC. Tests for heterogeneity and horizontal pleiotropy were performed.

As ALM increases, the risk of HCC occurrence decreases [odds ratio (OR), 95% confidence interval (CI): 0.703, 0.524-0.943; P = 0.019]. And, genetically predicted low-HGS (OR, 95%CI: 2.287, 1.013-5.164; P = 0.047) was associated with an increased incidence risk of HCC, with no reverse causality. However, we found no evidence supporting a causality between WP and HCC. CRP was identified as the mediator of the causal effect of ALM and low-HGS on HCC, with corresponding mediating effects of 9.1% and 7.4%.

This MR study effectively demonstrates that lower ALM and low-HGS are linked to an elevated risk of HCC within the European population, and the causality was not bidirectional. Furthermore, CRP serves as a mediator in the associations. These findings may help mitigate HCC risk among individuals with sarcopenia.

Sarcopenia and sarcopenic obesity are associated with an increased possibility of adverse clinical outcomes; however, the effects of sarcopenia and sarcopenic obesity on patients with primary liver cancer remain controversial. Therefore, the present study aimed to determine the impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer.

We searched studies published in English in PubMed, Embase, Web of Science, and Cochrane Library databases up to 13 November 2022. Cohort studies that reported the association among sarcopenia, sarcopenic obesity, and patient survival were included.

A total of 64 cohort studies with data on 11,970 patients with primary liver cancer were included in the meta-analysis. Sarcopenia was associated with poor overall survival in patients with primary liver cancer [adjusted hazard ratio (HR) 2.11, 95% confidence interval (CI): 1.89-2.36, P < 0.0001], with similar findings for sarcopenic obesity (adjusted HR: 2.87, 95% CI: 2.23-3.70, P < 0.0001). Sarcopenia was also associated with poor overall survival across the subgroups analyzed by ethnicity, type of liver cancer, treatment modalities, method used to define sarcopenia, and etiology of liver cancer. We also found a negative correlation among sarcopenia, sarcopenic obesity, and recurrence-free/disease-free survival (adjusted HR: 1.73, 95% CI: 1.50-1.99, P < 0.001; adjusted HR: 2.28, 95% CI: 1.54-3.35, P < 0.001, respectively).

Sarcopenia and sarcopenic obesity were significantly associated with poor overall survival and recurrence-free/disease-free survival in patients with primary liver cancer.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378433, PROSPERO [42022378433].

Interstitial brachytherapy (iBT) is an effective treatment for hepatocellular carcinoma (HCC). Identification of prognostic factors is pivotal for patient selection and treatment efficacy. This study aimed to assess the impact of low skeletal muscle mass (LSMM) on overall survival (OS) and progression-free survival (PFS) of iBT in patients with HCC.

For this single-center study, we retrospectively identified 77 patients with HCC who underwent iBT between 2011 and 2018. Follow-up visits were recorded until 2020. The psoas muscle area, psoas muscle index, psoas muscle density (MD), and the skeletal muscle gauge were assessed on the L3 level on pre-treatment cross-sectional CT scans.

Median OS was 37 months. 42 patients (54.5%) had LSMM. An AFP level of >400 ng/ml (hazard ratio [HR] 5.705, 95% confidence interval [CI]: 2.228-14.606, p = 0.001), BCLC stage (HR 3.230, 95% CI: 0.972-10.735, p = 0.026), and LSMM (HR 3.365, 95% CI: 1.490-7.596, p = 0.002) showed a relevant association with OS. Weighted hazard ratios were used to form a predictive risk stratification model with three groups: patients with low risk (median OS 62 months), intermediate risk (median OS 31 months), and high risk (median OS 9 months). The model showed a good prediction of 1-year mortality, with an AUC of 0.71. Higher MD was associated with better PFS (HR 0.920, 95% CI: 0.881-0.962, p < 0.001).

In patients undergoing iBT for HCC, LSMM is associated with worse OS. A risk stratification model based on LSMM, AFP >400 ng/mL, and BCLC stage successfully predicted patient mortality. The model may support and enhance patient selection.

To explore the association between risk factors established in the surgical literature and hospital length of stay (HLOS), adverse events, and hospital readmission within 30 days after percutaneous image-guided thermal ablation of lung tumors.

This bi-institutional retrospective cohort study included 131 consecutive adult patients (67 men [51%]; median age, 65 years) with 180 primary or metastatic lung tumors treated in 131 sessions (74 cryoablation and 57 microwave ablation) from 2006 to 2019. Age-adjusted Charlson Comorbidity Index, sex, performance status, smoking status, chronic obstructive pulmonary disease (COPD), primary lung cancer versus pulmonary metastases, number of tumors treated per session, maximum axial tumor diameter, ablation modality, number of pleural punctures, anesthesia type, pulmonary artery-to-aorta ratio, lung densitometry, sarcopenia, and adipopenia were evaluated. Associations between risk factors and outcomes were assessed using univariable and multivariable generalized linear models.

In univariable analysis, HLOS was associated with current smoking (incidence rate ratio [IRR], 4.54 [1.23-16.8]; P = .02), COPD (IRR, 3.56 [1.40-9.04]; P = .01), cryoablations with ≥3 pleural punctures (IRR, 3.13 [1.07-9.14]; P = .04), general anesthesia (IRR, 10.8 [4.18-27.8]; P < .001), and sarcopenia (IRR, 2.66 [1.10-6.44]; P = .03). After multivariable adjustment, COPD (IRR, 3.56 [1.57-8.11]; P = .003) and general anesthesia (IRR, 12.1 [4.39-33.5]; P < .001) were the only risk factors associated with longer HLOS. No associations were observed between risk factors and adverse events in multivariable analysis. Tumors treated per session were associated with risk of hospital readmission (P = .03).

Identified preprocedural risk factors from the surgical literature may aid in risk stratification for HLOS after percutaneous ablation of lung tumors, but were not associated with adverse events.

Sarcopenia-related factors, including the skeletal muscle index (SMI), are reportedly associated with prognosis in patients with hepatocellular carcinoma (HCC) receiving various treatments. However, there is no evidence relating to hepatic arterial infusion chemotherapy (HAIC). In this study, we investigated whether a low SMI was associated with worse clinical outcomes of HAIC. Seventy patients with advanced HCC were included. Clinical outcomes were compared between the decreased SMI (n = 27) and non-decreased SMI (n = 43) groups, which were classified according to changes in the SMI after 3 weeks of treatment. In the prognostic analysis, patients in the decreased SMI group had significantly shorter progression-free and overall survival (OS) than those in the non-decreased SMI group. In addition, poor nutritional status and liver function were associated with an immediate decrease in the SMI after HAIC. The therapeutic effect was worse in the decreased SMI group than in the non-decreased SMI group, although the incidence of adverse events did not significantly differ. In multivariate analysis, a decreased SMI at 3 weeks after HAIC was identified as a significant independent factor associated with OS. A decreased SMI in patients with advanced HCC undergoing HAIC was associated with poor prognosis. It is effective to monitor the SMI to evaluate general conditions and predict clinical outcomes.

Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression-free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2-47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73-2.17, P < 0.001), higher risk of tumor recurrence (HR: 1.75, 95% CI 1.56-1.96, P < 0.001), lower objective response rate (OR: 0.37 95% CI 0.17-0.81, P = 0.012), and more drug-related adverse events (OR: 2.23, 95% CI 1.17-4.28, P = 0.015) in HCC patients. The subgroup analyses revealed that the OS of patients at the early stage of tumor was more severely affected by sarcopenia than for patients at other stages. Moreover, the presence of cirrhosis and Child Pugh class B increased the hazard of mortality from sarcopenia. This study has shown that sarcopenia is highly associated with poor prognosis in HCC patients. In addition, cirrhosis and poor liver functional reserve increase the danger of sarcopenia. OS was more impaired in HCC patients with sarcopenia at early stage of tumor than at other tumor stages.

Sarcopenia, characterized by the loss of muscle mass, strength, and physical ability, occurs with aging and certain chronic illnesses such as chronic liver diseases and cancer. Sarcopenia is common in liver cirrhosis and hepatocellular carcinoma (HCC). Previous reports of association between sarcopenia and prognosis of HCC have been inconsistent. Therefore, the present systematic review and meta-analysis aimed to investigate the impact of sarcopenia on the survival of patients with HCC.

A systematic literature search was conducted using PubMed, EMBASE, and Web of Science electronic databases from inception to May 1, 2022. We included retrospective or prospective studies investigating the association between sarcopenia and overall survival (OS) and/or progression free survival (PFS) of HCC. We applied the Quality in Prognosis Studies (QUIPS) instrument to evaluate the risk of bias and quality of included studies. The primary and secondary outcomes were the associations of sarcopenia with OS and PFS, respectively, expressed by a pooled hazard ratio (HR) and corresponding 95% confidence interval (CI). Subgroup analysis and sensitivity analysis were performed. We further evaluated the publication bias by the funnel plot and Begg's test.

A total of 42 studies comprising 8,445 patients were included. The majority of included studies were at an overall low risk of bias. The pooled prevalence of sarcopenia was 39% (95% CI: 33-45%) (n = 8,203). Sarcopenia was associated with an increased risk of shorter OS, with a pooled adjusted HR of 1.84 (95% CI: 1.62-2.09). An independent association between sarcopenia and reduced PFS was observed (HR = 1.33, 95% CI: 1.12-1.56).

The prevalence of sarcopenia was approximately 39% among patients with HCC. Sarcopenia was independently associated with reduced OS and PFS in HCC irrespective of treatment modalities. It is imperative that interventions aimed at alleviating sarcopenia and restoring muscle mass be implemented in order to improve the survival of patients with HCC.

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337797], identifier [CRD42022337797].

In the last decade, body composition (BC) assessment has emerged as an innovative tool that can offer valuable data concerning nutritional status in addition to the information provided by the classical parameters (i.e., body mass index, albumin). Furthermore, published data have revealed that different types of body composition are associated with different outcomes. For example, abnormalities of skeletal muscle, a common finding in cirrhotic and oncologic patients, are associated with poor outcome (i.e., high morbidity and high mortality). The disposition (visceral/subcutaneous adipose tissue) and radiodensity of adipose tissue proved to also be determinant factors for HCC outcome. Despite all the advantages, BC assessment is not part of the standard pre-therapeutic workup. The main reasons are the high heterogeneity of data, the paucity of prospective studies, the lack of a standard assessment method, and the interpopulation variation of BC. This paper aims to review the available evidence regarding the role of BC as a prognostic tool in the HCC population undergoing various therapies.

Liver cancer is the second most occurring cancer worldwide and is one of the leading causes of cancer-related deaths. Hepatocellular carcinoma (HCC) is the most common (80%-90%) type among malignant liver cancers. Sarcopenia occurs very early in HCC and can predict and provide an opportunity to improve muscle health before engaging in the treatment options such as loco-regional, systemic, and transplant management. Multiple prognostic stating systems have been developed in HCC, such as Barcelona Clinic Liver Cancer, Child-Pugh score and Albumin-Bilirubin grade. However, the evaluation of patients' performance status is a major limitation of these scoring systems. In this review, we aim to summarize the current knowledge and recent advances about the role of sarcopenia in cirrhosis in general, while focusing specifically on HCC. Additionally, the role of sarcopenia in predicting clinical outcomes and prognostication in HCC patients undergoing loco-regional therapies, liver resection, liver transplantation and systematic therapy has been discussed. A literature review was performed using databases PubMed/MEDLINE, EMBASE, Cochrane, Web of Science, and CINAHL on April 1, 2021, to identify published reports on sarcopenia in HCC. Sarcopenia can independently predict HCC-related mortality especially in patients undergoing treatments such as loco-regional, surgical liver transplantation and systemic therapies. Basic research is focused on evaluating a balance of anabolic and catabolic pathways responsible for muscle health. Early clinical studies have shown promising results in methods to improve sarcopenia in HCC which can potentially increase prognosis in these patients. As sarcopenia occurs very early in HCC, it can predict and provide an opportunity to improve muscle health before engaging in the treatment options such as loco-regional, systemic, and transplant management. Further, sarcopenia measurement can obviate the confounding caused by the abdominal ascites in these patients. The use of sarcopenia can add to the existing scoring systems to better prognosticate the HCC.

There are limited data from prospective studies showing the clinical usefulness of the new criteria for sarcopenia in liver disease produced by the Japan Society of Hepatology. Therefore, we aimed to evaluate the clinical usefulness of this new criteria for prognosis in cirrhotic patients.

This prospective study was performed at six centers. The 300 enrolled patients, aged more than 20 years with liver cirrhosis, were evaluated over a 3-year period for skeletal muscle mass index and grip strength. Sarcopenia was defined according to the Japan Society of Hepatology criteria by grip strength and computed tomography-based skeletal muscle mass index values. We investigated the correlation between sarcopenia and the survival rate of cirrhotic patients.

Among the 300 assessed patients there were 99 (33%) patients with sarcopenia. The number of deaths in the sarcopenia and non-sarcopenia groups was 34 (34.3%) and 38 (18.9%), respectively (p = 0.002). Multivariate analysis confirmed that sarcopenia, decompensated phase, albumin-bilirubin grade, and hepatocellular carcinoma (HCC) stage 3/4 were independent factors correlated with death in patients with liver cirrhosis during the observation period. The interaction between sarcopenia and the presence of HCC was statistically significant (p < 0.001), and the presence of HCC had the highest hazard ratio of 6.665 for deaths in cirrhotic patients when non-sarcopenia and the absence of HCC were used as references.

The new Japan Society of Hepatology criteria for sarcopenia are accurate predictors of poor prognosis in patients with liver cirrhosis.

Radiofrequency ablation (RFA) appears effective for the treatment of hepatocellular carcinoma (HCC). Evaluation of prognostic factors is imperative for patient selection and improving treatment efficacy. This study aimed to assess sarcopenia as a predictor of the outcome of RFA in patients with HCC.

This prospective study included all patients with HCC on top of HCV-related cirrhosis who underwent RFA and followed up for a minimum of two years. CT scan was used to determine the skeletal muscle index at the psoas, erector spinae, quadratus lumborum, transversus abdominis, external and internal obliques, and rectus abdominis muscles. Cross-sectional areas were calculated to obtain a lumbar skeletal muscle index (L3-SMI).

A total of 97 patients were enrolled in the study. The L3-SMI was 46.2±12.1 cm2/m2. Older age was the only risk factor associated with sarcopenia (p = 0.001). The overall survival at two years for the whole group was 65.2%. Sarcopenia and MELD score were independent predictors of OS at two years with HR of 7.6 (95% CI: 3.1-18.7) and 2.2 (95% CI: 1.0-4.8), respectively. Recurrence-free survival was 84.1% at two years. Recurrence was not affected by all factors, including sarcopenia.

Sarcopenia is a surrogate predictor of overall survival at two years in HCC patients after RFA. Sarcopenia assessment might be an additional prognostic indicator with conventional biomarkers to optimize the selection criteria for receiving RFA for early-stage HCC.