Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

Table 1 Description of population features according to presence of sarcopenia or not

	Overall cohort (n = 225)	Sarcopenia (n = 130)	No sarcopenia (n = 95)	P value
Clinical and biological features
Age (years old)1	65 (58-75)	67.5 (59.25-76)	62.5 (57-72.5)	0.0338
Gender2	200 (88.8%)	120 (92%)	80 (84%)	0.0841
Alcohol2	138 (61%)	72 (55%)	66 (69%)	0.04
NASH2	66 (29%)	28 (22%)	38 (40%)	0.003
HCV2	64 (28%)	42 (32%)	22 (23%)	0.14
HBV2	21 (9%)	11 (8%)	10 (11%)	0.65
Cirrhosis2	206 (91.5%)	116 (89.2%)	90 (94.7%)	0.1554
Platelets (103/mm3)1	123 (83-180)	131 (83.5-198.3)	113 (82-169)	0.1561
Creatinine (μmol/L)	77 (64-89)	77 (64-90)	77 (65-89)	0.93
Total bilirubin (μmol/L)	16 (9.9-22)	15.8 (9-22)	16 (10-22)	0.55
Albumin (g/dL)	36 (32-39)	35 (32-38)	36 (32-40)	0.11
AFP (ng/mL)1	10 (4.3-49)	11.5 (5.135-76.5)	7.7 (4-25.5)	0.0152
Child-Pugh A2	184 (81.57%)	105 (80.7%)	79 (83.2%)	0.728
MELD	8.7 (7-11)	8.5 (7.6-10)	9.1 (7.3-11)	0.53
BCLC-A2	62 (27.5%)	33 (25.3%)	29 (30.5%)	0.1796
BCLC-B2	125 (55.5%)	70 (53.8%)	55 (57.89%)
BCLC-C2	38 (16.8%)	27 (20.76%)	11 (11.57%)
Segmental portal vein thrombosis2	34 (15.1%)	24 (18.46%)	10 (10.5%)	0.1314
Type of treatment
TACE2	154 (68.4%)	86 (66.6%)	68 (71.5%)	0.4681
Bland embolization2	71 (31.5%)	43 (33.3%)	27 (28.4%)	0178
Number of procedures per patient1	2 (1-3)	2 (1-2)	2 (1-3)	0.0178
Body mass index1	26.4 (23.5-29.18)	24.3 (22.3-26.9)	28.7 (26.4-32.33)	< 0.0001
Oesophageal varices2	107 (49.3%)	61 (48.4%)	46 (50.5%)	0.784
Radiological features
Size of the largest nodule (mm)1	37 (24-61)	40 (24-70)	34 (23-53)	0.0665
Multiples nodules2	169 (75.1%)	99 (76.1%)	70 (73.7%)	0.7552
Skeletal muscle index (cm2/m2)1	47.12 (41.75-53.2)	42.85 (38.61-46.79)	54.19 (51.38-58.27)	< 0.0001
Psoas muscle index (cm2/m2)1	10 (8.575-11.94)	9.205. (8.087-10.97)	11.51 (9.679-14.26)	< 0.0001
Psoas L3 (cm2)1	17 (14.72-37.27)	15.95 (13.95-18.7)	19.8 (16.6-23.8)	< 0.0001
Muscle L3 (cm2)1	137 (119.3-155.4)	125.8 (113.8-138.1)	156.2 (145-176)	< 0.0001
Umbilical vein repermeabilization2	82 (36.4%)	51 (39.2%)	31 (32.6%)	0.3292
Oesophageal varices2	160 (71.1%)	91 (70%)	69 (72%)	0.7661
Ascites2	53 (23.5%)	29 (22.3%)	24 (25.2%)	0.6355
Liver/spleen volume ratio1	4.346 (2.885-6.798)	4.562 (2.927-7.205)	3.797 (2.605-6.187)	0.1085
Liver volume (cm3)1	1715 (1430-2071)	1701 (1407-1978)	1800 (1461-2142)	0.0833
Spleen volume (cm3)1	414 (252-606)	382 (230.5-573.3)	480 (308-634)	0.0283
Splenomegaly2	129 (57.6%)	71 (55%)	58 (61%)	0.4127
Treatments following TAE/TACE
Curative-intent
Liver resection	2 (0.9%)	1 (0.8%)	1 (1.1%)
RFA/Microwaves/Alcoholization	27 (12.0%)	14 (10.8%)	13 (13.7%)
Liver transplantation	46 (20.4%)	19 (14.6%)	27 (28.4%)
Palliative-intent
SIRT	2 (0.9%)	2 (1.5%)	0
Sorafenib	44 (19.6%)	28 (21.5%)	16 (16.8%)
Other systemic treatments	8 (3.6%)	4 (3.1%)	4 (4.2%)
No additional treatment	82 (36.4%)	50 (38.5%)	32 (33.7%)

¹Median (25^th-75^th percentiles).

²Numbers (percentages).

AFP: Alpha-fetoprotein; BCLC: Barcelona clinic liver cancer staging system; HCV: Hepatitis C virus; HBV: Hepatitis B virus; NASH: Non-alcoholic steatohepatitis; RFA: Radiofrequency ablation; SIRT: Selective internal radiation therapy; TACE: Trans-arterial chemoembolization.

Table 2 Univariate and multivariate Cox analyses of baseline variables associated with progression-free survival

Variable	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Sarcopenia (yes vs no, imaging)	1.58	1.17-2.15	0.003	1.62	1.15-2.28	0.006
Skeletal muscle index (imaging)1	0.91	0.98-1.01	0.306
Psoas muscle index (imaging)1	0.97	0.92-1.02	0.18
Paraombilical vein (imaging)	1.21	0.88-1.65	0.24
Esophageal varices (imaging)	0.94	0.68-1.30	0.72
Ascites (imaging)	1.38	0.97-1.97	0.07
Liver/spleen ratio (imaging)1	1.02	0.98-1.07	0.21
Liver volume (imaging)1	1.00	1.00-1.00	0.062
Spleen volume (imaging)1	0.99	0.99-1.00	0.54
Splenomegaly (imaging)	1.18	0.87-1.60	0.28
BCLC stage	1.24	0.98-1.58	0.068
Multiple nodules	1.03	0.73-1.45	0.88
Portal vein thrombosis	1.58	1.05-2.39	0.03	1.77	1.11-2.83	0.02
Size of the largest nodule1	1.01	1.00-1.01	0.0003	1.008	1.002-1.013	0.006
Esophageal varices at endoscopy	0.98	0.72-1.33	0.88
Serum AFP1	1.00	1.00-1.00	0.0007	1.0001	1.00001-1.00002	0.07
Platelets1	1.00	1.00-1.01	0.002	1.002	1.0001-1.005	0.04
Child Pugh B7	1.02	0.67-1.56	0.93
Creatinin1	1.00	0.99-1.01	0.097
Prothrombin time1	1.00	0.99-1.01	0.68
Total bilirubin1	0.99	0.99-1.01	0.99
Albumin1	0.99	0.97-1.03	0.84
Clinical ascites	1.00	0.63-1.59	0.99
Cirrhosis	0.87	0.53-1.45	0.60
NASH	1.21	0.60-1.14	0.24
HCV	0.85	0.61-1.18	0.32
HBV	0.73	0.41-1.28	0.27
Alcohol intake	1.013	0.75-1.37	0.93
Body mass index1	0.98	0.95-1.01	0.21
Gender (Male)	1.37	0.86-2.19	0.19
Age (years old)1	1.00	0.99-1.02	0.68

¹Parameters expressed as continuous variables.

Sarcopenia was analyzed as a categoric factor (yes vs no). AFP: Alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; HCV: Hepatitis C virus; HBV: Hepatitis B virus; NASH: Non alcoholic steatohepatitis.

Table 3 Univariate and multivariate Cox analyses of baseline variables associated with overall survival

Variable	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Sarcopenia (yes vs no, imaging)	1.57	1.09-2.27	0.016	1.68	1.04- 2.72	0.03
Skeletal muscle index (imaging)1	0.99	0.97-1.01	0.19
Psoas muscle index (imaging)1	0.95	0.89-1.01	0.14
Paraombilical vein (imaging)	1.16	0.80-1.66	0.43
Esophageal varices (imaging)	1.09	0.75-1.61	0.63
Ascites (imaging)	1.74	1.16-2.60	0.007	1.59	0.97-2.60	0.07
Liver/spleen ratio (imaging)1	1.03	0.98-1.08	0.13
Liver volume (imaging)1	1.00	0.99-1.00	0.86
Spleen volume (imaging)1	0.99	0.99-1.00	0.19
Splenomegaly (imaging)	0.95	0.66-1.35	0.77
BCLC stage	1.28	0.97-1.68	0.08
Multiple nodule	0.83	0.56-1.22	0.34
Portal vein thrombosis	1.52	0.98-2.38	0.06
Size of the largest nodule1	1.01	1.00-1.01	0.003	1.007	1.0015-1.013	0.014
Esophageal varices (endoscopy)	1.17	0.82-1.69	0.38
AFP1	1.00	1.00-1.00	0.00018	1.0001	1.00001-1.0002	0.006
Platelet1	1.00	0.99-1.00	0.170
Child-Pugh B7	2.04	1.21-3.45	0.007	1.59	0.86-2.96	0.14
Creatinin1	1.00	0.99-1.00	0.18
Prothrombin time1	1.01	0.98-1.01	0.45
Total bilirubin1	1.02	1.00-1.03	0.035
Albumin1	0.94	0.91-0.98	0.003
Clinical ascites	1.46	0.88-2.42	0.143
Cirrhosis	1.27	0.71-2.26	0.42
NASH	0.70	0.47- 1.04	0.075
HCV	1.32	0.89-1.95	0.17
HBV	0.71	0.33-1.54	0.39
Alcohol intake	1.05	0.67-1.37	0.80
Age (years old)1	1.00	0.99-1.02	0.79
BMI1	0.96	0.93-0.99	0.026	0.99	0.95-1.040	0.75
Gender (Male)	1.08	0.63-1.85	0.79

¹Parameters expressed as continuous variables.

Sarcopenia was analyzed as a categoric factor (yes vs no). AFP: Alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; HCV: Hepatitis C virus; HBV: Hepatitis B virus; NASH: Non alcoholic steatohepatitis; BMI: Body mass index.