A Novel Scoring System for Patients with Recurrence of Hepatocellular Carcinoma After Undergoing Minimal Invasive Therapies

Figures & data

Table 1 Demographic and Clinicopathological Data of HCC Patients

Variables	Mean ± SD/n(%)
Gender, male/female(%)	182(77.8%)/52(22.2%)
Age,≤60 years/>60 years(%)	142(60.7)/92(39.3)
History of smoking(%)	97(41.5%)
History of drinking(%)	75(32.1%)
Diabetes mellitus(%)	50(21.4%)
High blood pressure(%)	64(27.4%)
Cirrhosis(%)	179(76.5%)
Child-Pugh class, A/B(%)	153(65.4%)/81(34.6%)
Antiviral therapy(%)	124(53.0%)
Tumor number, solitary/multiple(%)	166(70.9%)/68(29.1%)
Tumor size, ≤30mm vs >30mm	150(65.5%)/84(34.5%)
Ablation method, RFA/MWA/AHC(%)	116(49.6%)/61(26.1%)/57(24.3%)
Etiology, HBV/HCV/ALD(%)	176(75.2%)/43(18.4%)/15(6.4%)
AFP(<7 ng/mL/7–400ng/mL/≥400ng/mL)	106(45.3%)/97(41.5%)31(13.2%)
Viral load(<100IU/mL/≥100IU/mL)	138(59.0%)/96(41.0%)
ALT(U/L)	37.85±20.44
AST(U/L)	31.89±12.22
Total serum bilirubin(μmol/L)	19.01±9.20
Neutrophil count(10^9/L)	3.26±1.65
Lymphocyte count(10^9/L)	1.22±0.56
Platelet count(10^9/L)	125.38±64.66
Globulin(g/L)	27.92±6.50
γ-GT(U/L)	76.27±102.62
Fibrinogen(g/L)	2.93±0.93
Blood urea nitrogen(mmol/L)	4.52±1.45
Total cholesterol(mmol/L)	3.76±0.81
APR	0.31±0.13

Abbreviations: RFA, radiofrequency ablation; MWA, microwave ablation; AHC, argon-helium cryoablation; HBV, hepatitis B virus; HCV, hepatitis C virus; ALD, alcohol liver disease; AFP, alpha-fetoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GT, gamma-glutamyltransferase; APR, albumin-to-prealbumin ratio, the APR was estimated as the albumin divided by the prealbumin.

Figure 1 Patients selection process.

Table 2 The Comparison of Clinical Data Between Recurrence/Non-Recurrence Group

Variables	Non-Recurrence	Recurrence	P Value
Gender, male/female(%)	88(73.3%)/32(26.7%)	94(82.5%)/20(17.5%)	0.093
Age, ≤60 years/>60 years(%)	69(57.5%)/51(42.5%)	73(64.0%)/41(36.0%)	0.306
History of smoking(%)	41(34.2%)	56(49.1%)	0.020
History of drinking(%)	35(29.2%)	40(35.1%)	0.332
Diabetes mellitus(%)	22(18.3%)	28(24.6%)	0.810
High blood pressure(%)	32(26.7%)	32(28.1%)	0.245
Cirrhosis(%)	86(71.7%)	93(81.6%)	0.074
Child-Pugh class, A/B(%)	86(71.7%)/34(28.3%)	67(58.8%)/47(41.2%)	0.038
Antiviral therapy(%)	69(58%)	55(49.1%)	0.176
Tumor number, solitary/multiple(%)	100(83.3%)/20(16.7%)	66(57.9%)/48(42.1%)	<0.0001
Tumor size, ≤30mm vs >30mm	85(70.8%)/35(29.2%)	65(57.0%)/49(43.0%)	0.028
Ablation method, RFA/MWA/AHC(%)	58(48.3%)/30(25.0%)/32(26.7%)	59(51.8%)/31(27.2%)/24(21.0%)	0.602
Etiology, HBV/HCV/others(%)	91(75.8%)/22(18.4%)/7(5.8%)	85(74.6%)/21(18.4%)/8(7.0%)	0.932
AFP(<7 ng/mL/7–400ng/mL/≥400ng/mL)	63(52.9%)/45(37.8%)/11(9.3%)	43(37.4%)/54(47.0%)/18(15.6%)	0.040
Viral load(<100IU/mL/≥100IU/mL)	75(63.6%)/43(36.4%)	69(59.5%)/47(40.5%)	0.320
ALT(U/L)	37.06±20.15	38.67±20.79	0.552
AST(U/L)	30.83±9.08	32.99±14.25	0.183
Total serum bilirubin(μmol/L)	18.83.06±9.40	19.20±9.03	0.763
Neutrophil count(10^9/L)	3.14±1.58	3.38±1.71	0.269
Lymphocyte count(10^9/L)	1.21±0.59	1.24±0.54	0.693
Platelet count(10^9/L)	121.24±56.86	129.67±71.86	0.322
Globulin(g/L)	27.16±5.01	28.77±7.65	0.058
γ-GT(U/L)	105.10	130.56	0.004
Fibrinogen(g/L)	2.78±0.88	3.08±0.96	0.016
Blood urea nitrogen(mmol/L)	4.82±1.50	4.21±1.34	0.001
Total cholesterol(mmol/L)	3.85±0.77	3.66±0.83	0.070
APR	0.29±0.11	0.34±0.15	0.002

Abbreviations: RFA, radiofrequency ablation; MWA, microwave ablation; AHC, argon-helium cryoablation; HBV, hepatitis B virus; HCV, hepatitis C virus; ALD, alcohol liver disease; AFP, alpha-fetoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GT, gamma-glutamyltransferase; APR, albumin-to-prealbumin ratio, the APR was estimated as the albumin divided by the prealbumin.

Table 3 Prognostic Factors for RFS by Cox Proportional Hazards Regression Model

Variables	Univariate		Multivariate
HR (95% CI)	P value	HR (95% CI)	P value
Gender	1.72(1.10–2.69)	0.017	1.87(1.08–3.23)	0.024
History of smoking	1.51(1.08–2.10)	0.014	1.07(0.73–1.58)	0.708
Cirrhosis	1.28(0.85–1.92)	0.225
Child-Pugh class	1.27(0.90–1.78)	0.164
Antiviral therapy	0.77(0.55–1.08)	0.138
Tumor number	2.36(1.68–3.32)	<0.0001	1.88(1.30–2.71)	0.001
Tumor size	1.61(1.15–2.24)	0.005	0.97(0.63–1.47)	0.890
AFP	1.46(1.15–1.85)	0.002	1.30(1.02–1.67)	0.033
AST	1.01(0.99–1.02)	0.062
Globulin	1.03(1.00–1.06)	0.012	1.22(1.01–1.49)	0.075
γ-GT	1.00(0.99–1.00)	0.012	1.00(0.99–1.00)	0.269
Fibrinogen	1.32(1.12–1.55)	0.001	1.22(1.01–1.49)	0.038
Blood urea nitrogen	0.85(0.76–0.96)	0.010	0.90(0.79–1.03)	0.151
Total cholesterol	0.81(0.65–1.00)	0.053
APR	4.37(1.42–13.42)	0.010	3.90(1.02–14.89)	0.046

Abbreviations: AFP, alpha-fetoprotein; AST, aspartate aminotransferase; γ-GT, gamma-glutamyltransferase; APR, albumin-to-prealbumin ratio, the APR was estimated as the albumin divided by the prealbumin.

Table 4 The Assignment of Variables According HR

Variables	HR	Score
Gender	1.87
Female		0
Male		2
Tumor number	1.88
Single		0
Multiple		2
AFP(ng/mL)	1.3
<7 ng/mL		0
7–400ng/mL		1
≥400ng/mL		2
Fibrinogen(mg/dL)	1.23
<3.105mg/dL		0
≥3.105mg/dL		1
APR	3.9
<0.250		0
≥0.250		4

Abbreviations: AFP, alpha-fetoprotein; APR, albumin-to-prealbumin ratio, the APR was estimated as the albumin divided by the prealbumin.

Table 5 The Comparison of Clinical Data Among Groups with Different Recurrence Risk

Variables	Low-Risk Group	Intermediate-Risk Group	High-Risk Group	P Value
Age,≤60 years/>60 years	32/17	72/52	35/20	0.609
History of smoking, yes/no	13/36	50/74	31/24	0.008
History of drinking, yes/no	13/36	37/87	22/33	0.278
Cirrhosis, yes/no	32/17	99/25	46/9	0.056
Antiviral therapy, yes/no	36/12	66/58	18/35	<0.0001
Child-Pugh class, A/B	42/7	75/49	30/25	0.002
Tumor size, ≤30mm/>30mm	43/6	81/43	23/32	<0.0001
Ablation method, RFA/MWA/AHC	23/7/19	65/32/27	25/22/8	0.008
Etiology, HBV/HCV/Alcohol	39/8/2	93/22/9	41/10/4	0.934
Viral load, <100IU/mL/≥100IU/mL	32/10	62/36	22/22	0.042
ALT(U/L)	33.85±17.10	35.70±18.72	45.74±24.22	0.003
AST(U/L)	29.20±11.22	30.96±10.88	35.85±14.55	0.012
Total serum bilirubin(μmol/L)	17.98±9.65	19.49±9.81	19.07±7.65	0.632
Neutrophil count (10^9/L)	3.53±1.70	3.12±1.64	3.39±1.67	0.312
Lymphocyte count (10^9/L)	1.27±0.54	1.18±0.57	1.26±0.60	0.585
Platelet count (10^9/L)	129.19±49.59	122.52±68.15	129.62±71.54	0.733
Globulin(g/L)	26.90±5.10	27.92±6.27	28.59±8.02	0.413
γ-GT(IU/L)	93.99	108.67	145.93	<0.0001
Blood urea nitrogen(mmol/L)	4.97±1.10	4.66±1.53	3.92±1.37	0.001
Total cholesterol(mmol/L)	3.98±0.77	3.76±0.87	3.56±0.66	0.034

Abbreviations: RFA, radiofrequency ablation; MWA, microwave ablation; AHC, argon-helium cryoablation; HBV, hepatitis B virus; HCV, hepatitis C virus; ALD, alcohol liver disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GT, gamma-glutamyltransferase.

Figure 2 The association between γ-GT, BUN, and TC and different recurrence risk.

Abbreviations: γ-GT, gamma-glutamyltransferase; BUN, blood urea nitrogen; TC, total cholesterol.

Figure 3 The cumulative recurrence risk in different levels of γ-GT, BUN, and TC.

Abbreviations: γ-GT, gamma-glutamyltransferase; BUN, blood urea nitrogen; TC, total cholesterol.

Figure 4 Kaplan-Meier survival curve of RFS and OS for patients with different recurrence risk.

Abbreviations: RFS, recurrence-free survival; OS, overall survival.