Prevalence and role of low skeletal muscle mass (LSMM) in hepatocellular carcinoma. A systematic review and meta-analysis

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor disease in the world. The impact of sarcopenia on survival outcomes in patients with HCC has been studied, but the extent of the impact remains unclear. This systematic review and meta-analysis aimed to analyze the prevalence of low skeletal muscle mass (LSMM) as a surrogate parameter for sarcopenia in patients with HCC and its influence on survival parameters after various treatments in a large study population.Different databases such as MEDLINE, Cochrane database, and SCOPUS were screened for studies on sarcopenia, respectively LSMM and survival in HCC up to March 2021. Twenty-seven studies met the inclusion criteria. The methodological quality was analyzed via QUADAS-2. We investigated the prevalence of LSMM and its impact on overall and recurrence/disease-free survival.The prevalence of LSMM, defined by different cut-off values, was 38.5%. In patients with LSMM, overall survival (OS) was strongly impaired in univariable and multivariable analyses: HR = 1.84, 95% CI = 1.64-2.07, p < 0.00001 and HR = 1.89, 95% CI = 1.61-2.23, p < 0.00001, respectively. Subanalyses on patients treated with kinase inhibitors such as Sorafenib or Lenvatinib (4 studies) or hepatectomy (6 studies) showed lower overall survival in multivariable regression with HR = 2.24, 95% = 1.60-3.14, p < 0.00001 and HR = 2.17, 95% CI = 1.48-3.19, p < 0.00001, respectively. Patients with LSMM post-resection also showed lower recurrence-free survival with HR = 1.79, 95% CI = 1.28-2.50, p < 0.00001 in multivariable analysis.LSMM is very frequent in patients with HCC. Due to its impact on survival, there is a need for adequate treatment and prevention, which proves to be challenging due to its multifactorial nature. For future investigation, one should focus on prospective study protocols as well as standardized assessment methods and cut-off values.