Ectopic fat in liver and skeletal muscle is associated with shorter overall survival in patients with colorectal liver metastases

Abstract

Background Myosteatosis has been associated with shorter overall survival in cancer patients. The increase in ectopic fat might not be limited to skeletal muscle only and might also extend to other sites such as the liver, resulting in non‐alcoholic fatty liver disease (NAFLD). In this study, we assessed the relationship between myosteatosis and NAFLD and their association with overall survival in patients with colorectal liver metastases undergoing partial hepatectomy. Methods Patients were selected from a prospective cohort of 289 consecutive patients with colorectal liver metastases. All patients with a preoperative computed tomography (CT)‐scan and liver biopsy obtained during surgery were included. If available a second pre‐operative CT scan was used to calculate changes in body composition over time. Muscle radiation attenuation was defined as the average Hounsfield units on CT of all muscle tissue at the L3 level. Liver biopsies were graded by a liver pathologist using the steatosis, activity, and fibrosis scoring system for NAFLD. Results Two‐hundred and eighteen patients had an available liver biopsy of which 131 patients had two available pre‐operative CT scans with an average time interval of 3.2 months. One‐hundred and thirty‐five (62%) biopsies were classified as NAFLD. In multivariable Cox‐regression analysis, NAFLD [hazard ratio (HR): 1.8, 95%‐confidence interval (CI) 1.0–3.0, P = 0.037], increase in myosteatosis (HR 1.8, 95%‐CI 1.1–2.9, P = 0.018), and skeletal muscle loss (HR 1.7, 95%‐CI 1.0–2.9, P = 0.035) were independently associated with shorter overall survival while high visceral adipose tissue fat content was associated with longer overall survival (HR: 0.7, 95%‐CI 0.5–0.9, P = 0.014). Conclusions Ectopic fat content of liver as well as skeletal muscle tissue is independently associated with shorter overall survival in patients with colorectal liver metastases, while increased visceral adipose tissue fat content is associated with longer overall survival.

Imaging based body composition profiling and outcomes after oncologic liver surgery

“…By contrary, survival was linked to body composition in 3 studies ( 43 , 46 , 47 ). In a retrospective Dutch trial including 196 patients (roughly 20% having sarcopenia), the authors found both reduced RFS and OS of 8.7 vs. 15.1 months (p=0.002) and 23.8 vs. 59.8 months (p=0.001) respectively in sarcopenic vs. non-sarcopenic patients.…”

“…Van Dijk et al., showed from a prospective cohort of 289 CRLM patients that NAFLD (p=0.037), myosteatosis (p=0.018), and sarcopenia (p=0.035) were independently associated with shorter OS while high visceral adipose tissue fat content was associated with longer OS (p=0.014). The authors concluded that ectopic fat content in liver as well as skeletal muscle is independently associated with shorter OS in patients undergoing liver resection for CRLM ( 47 ). In a previous study including 99 CRLM patients, the same authors advocated a correlation between host-phenotype of adverse body composition features (sarcopenia, low visceral adipose tissue) and systemic inflammation (C-reactive protein >5 mg/mL).…”

Validation of a deep learning model for automatic segmentation of skeletal muscle and adipose tissue on L3 abdominal CT images

“…Body composition is highly variable among sex, age, race, and cancer types. 3,4,[14][15][16] For this reason, developed clinical cut-offs vary greatly among different patient cohorts and prognostic models of outcome (e.g. survival) are likely to fail during external validation.…”

“…In particular, low skeletal muscle mass (i.e., sarcopenia), low adipose tissue mass, and decreased skeletal muscle radiodensity (i.e., myosteatosis) have been shown to be associated with shorter overall survival in various cancer types. [2][3][4] Body composition exhibits substantial heterogeneity among people due to natural variation in age, sex, race, and build. 5 These intrinsic inter-personal differences are unrelated to disease and may therefore obscure disease related body composition effects, necessitating large population-based data cohorts to adjust for them.…”

Combined impact of myosteatosis and liver steatosis on prognosis in stage I–III colorectal cancer patients

“…6 A previous study demonstrated that the presence of ectopic fat accumulation in the liver is independently associated with poorer overall survival (OS) in patients with colorectal liver metastasis (CRLM). 7 Prolonged storage of lipids in the liver can lead to liver dysfunction and inflammation, which play a crucial role in creating a metastatic-friendly environment that facilitates cancer seeding and colonization. 8 Moreover, CRLM patients with liver steatosis exhibit significantly shorter OS and hepatic recurrence-free survival.…”