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.

Keywords: Body composition; Colorectal liver metastases; Myosteatosis; Non-alcoholic fatty liver disease; Sarcopenia; Skeletal muscle loss.

Figure 1

Correlation matrix of all CT body composition variables. Values represent Pearson correlation coefficients (r). Only significant correlations (<0.05) are shown, white squares indicate insignificant correlations. L3‐indexes are a representation of whole‐body tissue mass and have been Z‐scored for sex and age. Δ parameters indicate changes between two pre‐operative CT scans in %/100 days. CT, computed tomography; RA, radiation attenuation; SAT, subcutaneous adipose tissue; TAT, total adipose tissue; VAT, visceral adipose tissue.

Figure 2

Venn diagram depicting the co‐existence of lipid accumulation in liver, skeletal muscle, and visceral adipose tissue. Numbers represent n patients. Liver steatosis was defined as at least steatosis Grade 1 on histology. Myosteatosis was defined as a skeletal muscle radiation attenuation Z‐score of <0. Increased VAT fat content was defined as a VAT radiation attenuation Z‐score of <0. VAT, visceral adipose tissue.

Figure 3

Cox regression analysis for overall survival. Liver steatosis and body composition variables were only kept in the multivariable model if P < 0.05. Liver steatosis was defined as a steatosis grade of ≥1. Z‐scores are included as continuous variables. Radiation attenuation (RA) is the average Hounsfield unit value of a certain type of tissue; a low RA is associated with a high tissue triglyceride content. Decrease/loss was defined as a Δ of <−2%/100 days. *P < 0.05. ASA, American Society of Anaesthesiologists; RA, radiation attenuation; VAT, visceral adipose tissue.

Figure 4

Cox‐regression analysis for disease‐free survival. Liver steatosis and body composition variables were eliminated from the multivariable model by stepwise backward elimination if P > 0.05. Liver steatosis was defined as a steatosis grade of ≥1. Z‐scores are included as continuous variables. Radiation attenuation (RA) is the average Hounsfield unit value of a certain type of tissue; a low RA is associated with a high tissue triglyceride content. Decrease was defined as a Δ of < −2%/100 days. *P < 0.05. ASA, American Society of Anaesthesiologists; RA, radiation attenuation; SAT, subcutaneous adipose tissue.