Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis

Abstract

Low 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.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors

“…This discrepancy may stem from smaller sample sizes and a different indicator of sarcopenia (SMI or PMI). Besides, Similar observations have been made in meta-analyses and follow-up studies ( 10 , 14 – 17 , 21 , 28 ), suggesting the clinical significance of sarcopenia in advanced HCC.…”

“…The incidence of grade ≥3 AEs was higher in sarcopenia patients(73.91% vs. 41.79%), potentially attributed to their diminished drug tolerance towards agents such as lenvatinib and PD-1 inhibitors. Additionally, dysfunction in direct pathways, such as alterations in the phosphatidylinositol-3-kinase/AKT-mammalian target of rapamycin (PI3K/AKT- mTOR) pathway, which plays a pivotal role in muscle protein synthesis, had been observed ( 14 ). The pathway of PI3K/AKT- mTOR will also lead to tumor progression ( 45 ).…”

The Negative Impact of Sarcopenia on Hepatocellular Carcinoma Treatment Outcomes

“…Furthermore, patients eligible for systemic therapy had a higher prevalence of sarcopenia compared to those treated with surgical or locoregional treatments, with prevalence ranging from 15% to 65% depending on geographical region and on the criteria used to define sarcopenia. The high prevalence of sarcopenia in patients with advanced HCC likely arises from the strict correlation between the progressive decline in skeletal muscle mass and the severity of malignancy [135]. The higher prevalence of sarcopenia among patients treated with systemic therapy is probably linked to its negative impact on treatment outcomes, as observed after surgery and locoregional therapies.…”

Prognostic significance of psoas muscle index in male hepatocellular carcinoma patients treated with immune checkpoint inhibitors and tyrosine kinase inhibitors

“… 30 , 31 Furthermore, studies have demonstrated that PMI is an independent predictor of overall survival in patients receiving nonsurgical treatments for HCC, such as hepatic arterial infusion chemotherapy (HAIC), TACE, or molecular targeted drugs like Sorafenib and Lenvatinib. 22 , 32 , 33 PMI is associated with sarcopenia and can be used to define sarcopenia. 34 Katsuya et al 35 reported that sarcopenia is not a prognostic factor in patients treated with Atezolizumab/Bevacizumab therapy.…”