(Supplementary table 1) Baseline characteristics of the patients

(Supplementary table 1) Baseline characteristics of the patients

Total (n=109)

Median age, years (range) 73 (34-88)

Sex, Male/Female 84/25

Cause of HCC, HBV/HCV/HBV+HCV/NBNC 16/66/1/26

Median BMI, kg/m² (range) 23.6 (16.2-41.9)

Sorafenib starting dose, 800/400/200 mg 40/67/2

C-P Child pugh score, 5/6 62/47

mALBI grade, 1/2a/2b 40/32/37

ECOG-PS, 0/1 94/15

Liver tumor size, cm 4.6 (0 – 20.5)

No. of tumors in liver, none/single/multiple 2/2/105

Extrahepatic metastasis 27 (24.8%)

MVI, Vp1+Vp2/Vp3/Vp4 11/15/3

Patients with > 50% liver occupation 6 (5.5%)

BCLC, A/B/C 2/55/52

Period from initial diagnosis to starting sorafenib, months (range) 31.6 (0.2 - 196.4)

Past history of TACE 82 (75.2%)

Median AFP, ng/mL (range) 82 (1.4 - 589420)

Median DCP, AU/mL (range) 275 (13 - 366930)

Median PMI, cm²/m²

Males (range) 5.93 (2.79-12.10)

Females (range) 4.30 (2.79-6.80)

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; BMI, body mass index; mALBI grade, modified

albumin-bilirubin grade; ECOG-PS, Eastern Cooperative Oncology Group performance status; MVI, major venous invasion; BCLC, Barcelona clinic liver cancer; TACE, transcatheter arterial chemoembolization; AFP, alpha‐

fetoprotein; DCP, des-gamma-carboxy prothrombin; PMI, psoas muscle index.

(Supplementary table 2) Factors associated with sorafenib tolerability Factor

multivariate analysis

OR 95%C.I. P value

Age (years) < 73 1.38 0.55-3.50 0.49

Sex Male 0.92 0.29-2.96 0.89

HCV or HBV Positive 3.07 0.90-10.50 0.073

BMI (kg/m²) <23.6 1.50 0.56-4.01 0.42

mALBI grade 1, 2a (vs.2b) 1.29 0.47-3.56 0.62

PS 1, 2 (vs.0) 0.21 0.03-1.24 0.084

BCLC stage C (vs.B) 0.73 0.26-2.04 0.55

Past history of TACE experienced 0.36 0.12-1.12 0.077

AFP (ng/mL) < 126.6 1.23 0.38-2.76 0.97

DCP (mAU/mL) < 266 1.36 0.48-3.17 0.67

PMI (cm²/m²) < cut off value* 0.22 0.08-0.59 0.002 OR, Odds ratio; HCV, hepatitis C virus; HBV, hepatitis B virus; BMI, body mass index; mALBI, modified albumin- bilirubin grade; PS, Eastern Cooperative Oncology Group performance status; BCLC, Barcelona clinic liver cancer;

TACE, transcatheter arterial chemoembolization; AFP, alpha‐fetoprotein; DCP, des-gamma-carboxy prothrombin;

PMI, psoas muscle index.

*: Male/Female 7.038/4.400

(Supplementary table 3A) Factors associated with time to treatment failure Factor

multivariate analysis

HR 95%C.I. P value

Age (years) < 73 0.84 0.53-1.31 0.43

Sex Male 1.60 0.95-2.66 0.075

HCV or HBV Positive 1.06 0.62-1.83 0.83

BMI (kg/m²) <23.6 0.94 0.60-1.49 0.80

mALBI grade 1, 2a (vs.2b) 0.71 0.45-1.13 0.146

PS 1, 2 (vs.0) 1.23 0.62-2.44 0.56

BCLC stage C (vs.B) 1.13 0.70-1.82 0.61

Past history of TACE experienced 1.10 0.65-1.88 0.71

AFP (ng/mL) < 126.6 0.75 0.48-1.16 0.193

DCP (mAU/mL) < 266 0.88 0.54-1.43 0.61

PMI (cm²/m²) < cut off value* 1.65 1.03-2.64 0.037 HR, hazard ratio; HCV, hepatitis C virus; HBV, hepatitis B virus; BMI, body mass index; mALBI, modified albumin-bilirubin grade; ECOG-PS, Eastern Cooperative Oncology Group performance status; BCLC, Barcelona clinic liver cancer; TACE, transcatheter arterial chemoembolization; AFP, alpha‐fetoprotein;

DCP, des-gamma-carboxy prothrombin; PMI, psoas muscle index. *: Male/Female 7.038/4.400

(Supplementary table 3B) Factors associated with overall survival time Factor

multivariable analysis

HR 95%C.I. P value

Age (years) < 73 0.60 0.37-0.96 0.032

Sex Male 1.51 0.88-2.58 0.133

HCV or HBV Positive 0.93 0.54-1.59 0.78

BMI (kg/m²) <23.6 1.22 0.75-1.98 0.42

mALBI grade 1, 2a (vs.2b) 0.56 0.35-0.89 0.014

PS 1, 2 (vs.0) 0.76 0.44-1.27 0.28

BCLC stage C (vs.B) 1.93 1.14-3.27 0.015

Past history of TACE experienced 0.75 0.44-1.27 0.28

AFP (ng/mL) < 126.6 0.68 0.42-1.09 0.111

DCP (mAU/mL) < 266 0.57 0.34-0.94 0.029

PMI (cm²/m²) < cut off value* 1.56 0.96-2.56 0.075 HR, hazard ratio; HCV, hepatitis C virus; HBV, hepatitis B virus; BMI, body mass index;mALBI, modified albumin-bilirubin grade; ECOG-PS, Eastern Cooperative Oncology Group performance status; BCLC, Barcelona clinic liver cancer; TACE, transcatheter arterial chemoembolization; AFP, alpha‐fetoprotein;

DCP, des-gamma-carboxy prothrombin; PMI, psoas muscle index. *: Male/Female 7.038/4.400

(Supplementary table 4) Factors associated with progression free survival Factor

multivariate analysis

HR 95%C.I. P value

Age (years) < 73 0.89 0.56-1.43 0.64

Sex Male 1.51 0.87-2.61 0.140

HCV or HBV Positive 1.20 0.68-2.10 0.54

BMI (kg/m²) <23.6 0.79 0.48-1.31 0.36

Child Pugh score 5 (vs.6) 1.13 0.68-1.86 0.64

PS 1, 2 (vs.0) 1.58 0.74-3.36 0.24

BCLC stage C (vs.B) 0.98 0.58-1.65 0.93

Past history of TACE experienced 0.94 0.53-1.68 0.83

AFP (ng/mL) < 126.6 0.82 0.51-1.32 0.41

DCP (mAU/mL) < 266 0.94 0.55-1.59 0.81

PMI (cm²/m²) < cut off value* 1.62 0.68-1.86 0.64 HR, hazard ratio; HCV, hepatitis C virus; HBV, hepatitis B virus; BMI, body mass index; ECOG-PS, Eastern Cooperative Oncology Group performance status; BCLC, Barcelona clinic liver cancer; TACE,

transcatheter arterial chemoembolization; AFP, alpha‐fetoprotein; DCP, des-gamma-carboxy prothrombin;

PMI, psoas muscle index. *: Male/Female 7.038/4.400

Supplementary Figure 1

Comparison of sorafenib tolerability in groups stratified according to PMI based on clinical sarcopenia

criteria. The cut-off value of PMI was based on the assessment criteria for sarcopenia in liver disease

proposed by the Japan Society of Hepatology (JSH). The cut-off values are 6.0 cm2/m2 in men and 3.4

cm2/m2 in women. This cut-off value stratified 51 of the 109 patients into the muscle atrophy group

and the remaining 58 patients into the non-muscle atrophy group.

Supplementary Figure 2

Association between PMI and progression-free survival (PFS) assessed by Kaplan-Meier analysis of 109

hepatocellular carcinoma (HCC) patients who received sorafenib treatment, stratified according to PMI.