Sarcopenia Imperils Postoperative Long-Term Survival in HCC Patients with Metabolic Dysfunction-Associated Fatty Liver Disease: A Propensity Score Matching Analysis

Figures & data

Figure 1 The red shaded part in the CT image represents the area of skeletal muscle. L3 SMI= 28.89 cm²/m². L3 SMI= 66.48 cm²/m².

Table 1 Baseline Characteristics of Patients of the Whole Study Population

	All Patients (n=112)	Sarcopenia (n=38)	Non-Sarcopenia (n=74)	P value
Age (years)	56.88±11.51	59.55±12.34	55.50±10.90	0.055
L3 SMI (cm²/ m²)	42.40±13.65	30.18±3.53	48.67±12.63	<0.001
BMI (kg/m²)	24.62±3.49	24.35±3.97	24.75±3.24	0.468
Tumor size (cm)	4.00(3.00–6.00)	4.00(2.80–6.00)	5.00(3.00–6.00)	0.467
Tumor number	1.00(1.00–1.00)	1.00(1.00–1.00)	1.00(1.00–1.00)	0.964
Total bilirubin (µmol/L)	14.00(11.30–19.10)	13.85(11.48–17.53)	14.05(10.78–20.98)	0.949
GGT (IU/L)	62.50(36.00–132.00)	56.50(35.50–115.00)	62.50(36.00–132.50)	0.842
ALT (IU/L)	37.00(24.25–54.50)	36.00(26.75–60.50)	38.00(22.75–52.25)	0.743
AST (IU/L)	36.00(24.00–59.00)	36.50(28.00–56.00)	35.00(23.00–67.25)	0.836
ALB (g/L)	41.02±5.22	41.27±5.94	40.90±4.84	0.376
HDL (mmol/L)	1.12(0.97–1.35)	1.15(0.98–1.31)	1.10(0.96–1.36)	0.788
LDL (mmol/L)	2.36(1.97–2.77)	2.32(1.98–2.78)	2.41(1.93–2.80)	0.549
TG (mmol/L)	1.31(0.87–1.71)	1.04(0.74–1.67)	1.35(0.94–1.72)	0.162
AFP (ng/mL)	14.38(3.83–258.58)	22.65(3.89–591.78)	13.08(3.77–228.38)	0.842
Gender, [n (%)]				0.655
Female	21(18.8%)	8(21.1%)	13(17.6%)
Male	91(81.3%)	30(78.9%)	61(82.4%)
BCLC stage				0.357
0	64(57.1%)	24(63.2%)	40(54.1%)
A	48(42.9%)	14(36.8%)	34(45.9%)
Child Pugh grade				0.095
A	77(68.8%)	30(78.9%)	47(63.5%)
B	35(31.2%)	8(21.1%)	27(36.5%)
Hypertension, [n (%)]				0.923
NO	73(65.2%)	25(65.8%)	48(64.9%)
YES	39(34.8%)	13(34.2%)	26(35.1%)
Diabetes, [n (%)]				0.249
NO	84(75.0%)	26(68.4%)	58(78.4%)
YES	28(25.0%)	12(31.6%)	16(21.6%)
Cirrhosis, [n (%)]				0.964
NO	74(66.1%)	25(65.8%)	49(66.2%)
YES	38(33.9%)	13(34.2%)	25(33.8%)
Ascites, [n (%)]				0.628
NO	110(98.2%)	37(97.4%)	73(98.6%)
YES	2(1.8%)	1(2.6%)	1(1.4%)
Satellite nodule, [n (%)]				0.798
NO	99(88.4%)	34(89.5%)	65(87.8%)
YES	13(11.6%)	4(10.5%)	9(12.2%)
Tumor thrombus, [n (%)]				0.701
NO	108(96.4%)	37(97.4%)	71(95.9%)
YES	4(3.6%)	1(2.6%)	3(4.1%)
Lymph node metastasis, [n (%)]				0.489
NO	108(96.4%)	36(94.7%)	72(97.3%)
YES	4(3.6%)	2(5.3%)	2(2.7%)
Extrahepatic metastasis, [n (%)]				0.701
NO	108(96.4%)	37(97.4%)	71(95.9%)
YES	4(3.6%)	1(2.6%)	3(4.1%)
HBV status, [n (%)]				0.580
Negative	49(43.8%)	18(47.4%)	31(41.9%)
Positive	63(56.3%)	20(52.6%)	43(58.1%)
HCV status, [n (%)]				0.208
Negative	107(95.5%)	35(92.1%)	72(97.3%)
Positive	5(4.5%)	3(7.9%)	2(2.7%)
MVI, [n (%)]				0.322
Negative	99(88.4%)	32(84.2%)	67(90.5%)
Positive	13(11.6%)	6(15.8%)	7(9.5%)
High differentiation, [n (%)]				0.257
NO	105(93.8%)	37(97.4%)	68(91.9%)
YES	7(6.3%)	1(2.6%)	6(8.1%)

Abbreviations: L3 SMI, L3 skeletal muscle index; BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; MAFLD, metabolic dysfunction-associated fatty liver disease; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ- glutamyl transpeptidase; TG, triglycerides; AFP, alpha-fetoprotein; BCLC, Barcelona clinic liver cancer; HDL, High-density lipoprotein; LDL, low-density lipoprotein; MVI, microvascular invasion.

Figure 2 RFS (A) and OS (B) after hepatectomy in MAFLD-HCC patients with or without sarcopenia before PSM.

Table 2 Univariate and Multivariate Analyses of Each Factor’s Value in Predicting RFS and OS of the Whole Study Population

	RFS				OS
	Univariate Analyses		Multivariate Analysis		Univariate Analyses		Multivariate Analysis
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Age. y
>60 vs ≤60	1.10(0.64–1.89)	0.745			2.52(0.91–6.95)	0.074
Gender
Male vs female	1.01(0.47–2.14)	0.986			0.36(0.13–0.99)	0.049	0.35(0.12–1.03)	0.056
BMI. kg/m²
≥23 vs <23	0.55(0.32–0.85)	0.032	0.57(0.33–0.99)	0.049	0.63(0.23–1.75)	0.372
Hypertension
With vs without	1.28(0.74–2.21)	0.375			1.66(0.62–4.48)	0.315
Diabetes
With vs without	1.27(0.71–2.28)	0.422			1.81(0.66–4.99)	0.250
Cirrhosis
With vs without	0.95(0.54–1.65)	0.845			2.07(0.77–5.59)	0.151
Ascites
With vs without	1.22(0.30–5.01)	0.786			0.05(0.00–41,181)	0.663
Satellite nodule
With vs without	3.55(1.70–7.39)	0.001	0.67(0.16–2.88)	0.589	3.45(0.97–12.29)	0.056
Tumor thrombus
With vs without	2.44(0.76–7.85)	0.135			7.21(1.61–32.31)	0.010	19.98(3.55–112.47)	0.001
Lymph node metastasis
With vs without	1.25(0.30–5.14)	0.762			0.05(0.00–22,287)	0.647
Extrahepatic metastasis
With vs without	2.65(0.82–8.56)	0.102			0.05(0.00–46,467)	0.665
HBV status
Positive vs negative	1.19(0.69–2.04)	0.539			0.83(0.31–2.22)	0.711
HCV status
Positive vs negative	3.07(1.18–8.00)	0.021	3.20(1.17–8.75)	0.023	1.53(0.20–11.72)	0.683
Tumor size. cm
>5 vs ≤5	1.02(0.57–1.83)	0.950			0.92(0.30–2.88)	0.888
Tumor number
Multiple vs single	1.36(0.66–2.79)	0.400			0.43(0.06–3.26)	0.414
Sarcopenia
With vs without	3.19(1.84–5.53)	<0.001	2.52(1.42–4.49)	0.002	3.74(1.32–10.56)	0.013	4.09(1.23–13.60)	0.022
BCLC stage
A vs 0	1.12(0.65–1.93)	0.689			0.77(0.27–2.21)	0.624
Child Pugh grade
B vs A	1.12(0.63–1.99)	0.701			1.47(0.53–4.04)	0.459
ALB. g/L
≤40 vs >40	0.69(0.40–1.19)	0.183			1.06(0.37–3.07)	0.909
Total bilirubin. µmol/L
>20.5 vs ≤20.5	1.34(0.74–2.40)	0.335			0.69(0.20–2.42)	0.558
ALT. IU/L
>50 vs ≤50	1.34(0.78–2.31)	0.291			0.78(0.27–2.24)	0.641
AST. IU/L
>40 vs ≤40	1.40(0.82–2.38)	0.221			0.76(0.28–2.10)	0.599
GGT. IU/L
>60 vs ≤60	1.52(0.89–2.60)	0.127			1.46(0.54–3.92)	0.455
TG. mmol/L
≥1.7 vs <1.7	1.06(0.58–1.93)	0.847			0.42(0.10–1.86)	0.253
AFP. ng/ml
≥400 vs <400	2.22(1.21–4.05)	0.01	2.30(1.24–4.25)	0.008	2.79(0.95–8.19)	0.063
HDL. mmol/L
<1.0 vs ≥1.0	1.26(0.72–2.21)	0.415			0.52(0.15–1.83)	0.309
LDL. mmol/L
≥3.4 vs <3.4	0.99(0.36–2.74)	0.984			0.80(0.11–6.05)	0.828
MVI
Positive vs negative	8.13(3.65–18.13)	<0.001	10.76(2.31–50.04)	0.002	6.23(1.72–22.58)	0.005	2.82(0.71–11.28)	0.142
High differentiation
NO vs YES	1.49(0.46–4.83)	0.51			1.86(0.24–14.32)	0.552

Note: A p-value less than 0.05 is displayed in bold black font, indicating a statistical difference between the two groups.

Abbreviations: BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; BCLC, Barcelona clinic liver cancer; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ- glutamyl transpeptidase; TG, triglycerides; AFP, alpha-fetoprotein; BCLC, Barcelona clinic liver cancer; HDL, High-density lipoprotein; LDL, low-density lipoprotein; CI, confidence interval; HR, hazard ratio; OS, overall survival from surgery to death; RFS, recurrence‐free survival after surgery; MVI, microvascular invasion.

Table 3 Baseline Characteristics of Patients in the Propensity Score Matching Cohort

	Patients After PSM (n=66)	Sarcopenia (n=33)	Non-Sarcopenia (n=33)	P value
Age (years)	56.14±11.66	58.30±12.57	53.97±10.42	0.132
L3 SMI (cm²/ m²)	40.02±13.08	30.46±3.39	49.57±12.14	<0.001
BMI (kg/m²)	24.68±3.42	24.73±4.00	24.62±2.77	0.900
Tumor size (cm)	4.00(3.00–6.00)	4.00(2.90–6.00)	5.00(3.00–5.05)	0.781
Tumor number	1.00(1.00–1.00)	1.00(1.00–1.00)	1.00(1.00–1.00)	1.000
Total bilirubin (µmol/L)	13.85(11.65–18.20)	14.00(11.65–17.95)	13.60(11.45–19.00)	0.768
GGT (IU/L)	52.00(34.75–107.75)	49.00(34.00–146.50)	54.00(34.50–80.00)	0.476
ALT (IU/L)	35.50(21.75–52.25)	36.00(25.50–54.00)	32.00(19.50–47.50)	0.336
AST (IU/L)	33.00(23.75–49.75)	36.00(25.00–55.50)	27.00(21.50–45.50)	0.084
ALB (g/L)	42.81±5.18	41.59±6.24	44.03±3.55	0.055
HDL (mmol/L)	1.14(0.97–1.32)	1.14(0.96–1.29)	1.14(0.98–1.52)	0.478
LDL (mmol/L)	2.51(2.12–2.78)	2.33(2.10–2.78)	2.62(2.21–2.90)	0.551
TG (mmol/L)	1.31(0.91–1.71)	1.12(0.80–1.71)	1.33(0.94–1.77)	0.305
AFP (ng/mL)	7.49(3.58–289.40)	10.45(3.87–390.00)	5.21(2.76–201.93)	0.307
Gender, [n (%)]				0.769
Female	15(22.7%)	7(21.2%)	8(24.2%)
Male	51(77.3%)	26(78.8%)	25(75.8%)
BCLC stage				0.800
0	41(62.1%)	21(63.6%)	20(60.6%)
A	25(37.9%)	12(36.4%)	13(39.4%)
Child Pugh grade				0.778
A	49(74.2%)	25(75.8%)	24(72.7%)
B	17(25.8%)	8(24.2%)	9(27.3%)
Hypertension, [n (%)]				0.602
NO	44(66.7%)	23(69.7%)	21(63.6%)
YES	22(33.3%)	10(30.3%)	12(36.4%)
Diabetes, [n (%)]				0.142
NO	51(77.3%)	23(69.7%)	28(84.8%)
YES	15(22.7%)	10(30.3%)	5(15.2%)
Cirrhosis, [n (%)]				0.447
NO	41(62.1%)	22(66.7%)	19(57.6%)
YES	25(37.9%)	11(33.3%)	14(42.4%)
Ascites, [n (%)]				0.314
NO	65(98.5%)	32(97%)	33(100.0%)
YES	1(1.5%)	1(3%)	0(0%)
Satellite nodule, [n (%)]				1.000
NO	60(90.9%)	30(90.9%)	30(90.9%)
YES	6(9.1%)	3(9.1%)	3(9.1%)
Tumor thrombus, [n (%)]				1.000
NO	64(97.0%)	32(97.0%)	32(97.0%)
YES	2(3.0%)	1(3.0%)	1(3.0%)
Lymph node metastasis, [n (%)]				0.314
NO	65(98.5%)	32(97.0%)	33(100.0%)
YES	1(1.5%)	1(3.0%)	0(0.0%)
Extrahepatic metastasis, [n (%)]				0.314
NO	65(98.5%)	32(97.0%)	33(100.00%)
YES	1(1.5%)	1(3.0%)	0(0.00%)
HBV status, [n (%)]				0.453
Negative	27(40.9%)	15(45.5%)	12(36.4%)
Positive	39(59.1%)	18(54.5%)	21(63.6%)
HCV status, [n (%)]				1.000
Negative	66(100.0%)	33(100.0%)	33(100.0%)
Positive	0(0.0%)	0(0.0%)	0(0.0%)
MVI, [n (%)]				1.000
Negative	56(84.8%)	28(84.8%)	28(84.8%)
Positive	10(15.2%)	5(15.2%)	5(15.2%)
High differentiation, [n (%)]				0.555
NO	63(95.5%)	32(97.0%)	31(93.9%)
YES	3(4.5%)	1(3.0%)	2(6.1%)

Abbreviations: L3 SMI, L3 skeletal muscle index; BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; MAFLD, metabolic dysfunction-associated fatty liver disease; BCLC, Barcelona clinic liver cancer; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ- glutamyl transpeptidase; TG, triglycerides; AFP, alpha-fetoprotein; HDL, High-density lipoprotein; LDL, low-density lipoprotein; MVI, microvascular invasion.

Figure 3 RFS (C) and OS (D) after hepatectomy in MAFLD-HCC patients with or without sarcopenia after PSM.