Simple SummaryThe association between low skeletal muscle mass (LSMM) and survival in HCC patients receiving systemic therapy remains inconclusive based on previous studies. Our study aimed to use meta-analysis to aggregate a large sample size and identify the association. The results confirmed that LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer overall survival and progression-free survival. This finding highlights the importance of evaluating muscle mass and early interventions to improve the survival of advanced HCC patients in clinical practice.AbstractLow skeletal muscle mass (LSMM) is associated with poor outcomes in hepatocellular carcinoma (HCC) patients. With the emergence of new systemic therapeutics, understanding the effect of LSMM on HCC treatment outcomes is critically important. This systematic review and meta-analysis investigates the prevalence and effect of LSMM among HCC patients undergoing systemic therapy as reported in studies identified in searches of the PubMed and Embase databases published through 5 April 2023. The included studies (n= 20; 2377 HCC patients undergoing systemic therapy) reported the prevalence of LSMM assessed by computer tomography (CT) and compared the survival outcomes [overall survival (OS) or progression-free survival (PFS)] between HCC patients with and without LSMM. The pooled prevalence of LSMM was 43.4% (95% CI, 37.0–50.0%). A random-effects meta-analysis showed that HCC patients receiving systemic therapy with comorbid LSMM had a lower OS (HR, 1.70; 95% CI, 1.46–1.97) and PFS (HR, 1.32; 95% CI, 1.16–1.51) than did those without. Subgroup analysis according to systemic therapy type (sorafenib, lenvatinib, or immunotherapy) yielded similar results. In conclusion, LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer survival. Early intervention or prevention strategies to improve muscle mass may be necessary for this patient population.