Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy

Table 1 Preoperative clinicopathologic data of patients with solitary hepatitis B virus-related hepatocellular carcinoma

Variables		N (1167)	Before PSM		P value	N (656)	After PSM		P value
			GPR ≤ 0.2 (n = 381)	GPR > 0.2 (n = 786)			GPR ≤ 0.2 (n = 328)	GPR > 0.2 (n = 328)
Sex	Male	985	278	707	< 0.001	533	266	267	1
	Female	182	103	79		123	62	61
Age (years)	≤ 50	654	229	425	0.059	377	196	181	0.269
	> 50	513	152	361		279	132	147
Body mass index	> 24	354	124	230	0.282	205	107	98	0.5
	≤ 24	813	257	556		451	221	230
Smoking	Yes	407	100	307	< 0.001	190	97	93	0.796
	No	760	281	479		466	231	235
Drinking	Yes	386	89	297	< 0.001	179	87	92	0.726
	No	781	292	489		477	241	236
Diabetes mellitus	Yes	59	15	44	0.284	33	15	18	0.721
	No	1108	366	742		623	313	310
Hypertension	Yes	114	38	76	0.953	67	33	34	1
	No	1053	343	710		589	295	294
Family history of liver cancer	Yes	128	41	87	0.954	72	39	33	0.532
	No	1039	340	699		584	289	295
Liver flukes	Yes	221	53	168	0.003	112	51	61	0.35
	No	946	328	618		544	277	267
Cirrhosis	Yes	587	158	429	< 0.001	280	145	135	0.477
	No	580	223	357		376	183	193
Serum alpha-fetoprotein (ng/mL)	≥ 200	440	164	276	0.011	246	139	107	0.012
	< 200	727	217	510		410	189	221
Child-Pugh	A	1151	378	773	0.355	649	325	324	1
	B	16	3	13		7	3	4
Barcelona Clinic Liver Cancer stage	0	172	65	107	0.142	103	53	50	0.83
	A	995	316	679		553	275	278
Total bilirubin (μmol/L)	> 20.5	128	31	97	0.04	73	28	45	0.047
	≤ 20.5	1039	350	689		583	300	283
Albumin (g/L)	> 40	534	223	311	< 0.001	354	184	170	0.309
	≤ 40	633	158	475		302	144	158
Gamma-glutamyl transpeptidase (U/L)	> 50	557	18	539	< 0.001	221	18	203	< 0.001
	≤ 50	610	363	247		435	310	125
Hepatitis B virus DNA (IU/mL)	> 1000	521	143	378	0.001	277	126	151	0.058
	≤ 1000	646	238	408		379	202	177
HBeAg status	-	299	619	918	0.914	259	252	511	0.510
	+	82	167	249		69	76	145
Antiviral therapy	No	265	521	786	0.264	233	221	454	0.310
	Yes	116	265	381		95	107	202
Surgical margin (cm)	< 2	169	308	477	0.092	146	127	273	0.132
	≥ 2	212	478	690		182	201	383
Tumor size (cm)	> 5	444	113	331	< 0.001	208	103	105	0.933
	≤ 5	723	268	455		448	225	223
Microvascular invasion	Yes	301	86	215	0.093	152	79	73	0.644
	No	866	295	571		504	249	255
Infiltrative growth	Yes	438	166	272	0.004	270	137	133	0.812
	No	729	215	514		386	191	195

P value: Calculated by Pearson's χ² test. PSM: Propensity score matching; GPR: Gamma-glutamyl transpeptidase-to-platelet ratio.

Table 2 Univariate and multivariate Cox-regression analyses predicting overall survival before and after propensity score matching

Variables	Before propensity matching				After propensity matching
	Uni-HR (95%CI)	P value	Multi-HR (95%CI)	P value	Uni-HR (95%CI)	P value	Multi-HR (95%CI)	P value
Sex (male/female)	1.44 (1.01-2.05)	0.043	1.3 (0.9-1.87)	0.159	1.22 (0.79-1.87)	0.364
Age (years) (> 50/≤ 50)	1.02 (0.81-1.29)	0.85			0.86 (0.63-1.19)	0.362
Body mass index (> 24/≤ 24)	1.16 (0.9-1.49)	0.255			1.25 (0.88-1.79)	0.218
Smoking (yes/no)	1.05 (0.83-1.34)	0.672			1.04 (0.74-1.48)	0.81
Drinking (yes/no)	0.9 (0.7-1.15)	0.412			0.85 (0.59-1.23)	0.388
Diabetes mellitus (yes/no)	0.75 (0.4-1.41)	0.372			0.46 (0.15-1.45)	0.186
Hypertension (yes/no)	0.82 (0.54-1.24)	0.345			0.66 (0.36-1.23)	0.192
Family cases (yes/no)	0.79 (0.53-1.17)	0.234			0.61 (0.34-1.1)	0.098
Liver flukes (yes/no)	0.88 (0.65-1.19)	0.392			0.75 (0.47-1.18)	0.214
Cirrhosis (yes/no)	1.21 (0.96-1.53)	0.1			1.24 (0.9-1.71)	0.18
Child-Pugh (B/A)	2.16 (1.07-4.36)	0.032	1.78 (0.87-3.63)	0.115	1.34 (0.33-5.42)	0.679
Barcelona Clinic Liver Cancer stage (A/0)	1.93 (1.31-2.83)	< 0.001	1.51 (1-2.26)	0.048	2.03 (1.19-3.45)	0.009	1.64 (0.94-2.86)	0.082
Total bilirubin (μmol/L) (> 20.5/≤ 20.5)	0.85 (0.6-1.21)	0.37			0.9 (0.55-1.45)	0.651
Albumin (g/L) (> 40/≤ 40)	1.35 (1.07-1.71)	0.012	1.16 (0.91-1.48)	0.229	1.2 (0.87-1.65)	0.26
Alpha-fetoprotein (ng/mL) (≥ 200/< 200)	1.38 (1.09-1.74)	0.006	1.35 (1.06-1.72)	0.013	1.37 (0.99-1.89)	0.055
Hepatitis B virus DNA (IU/mL) (> 1000/≤ 1000)	0.73 (0.58-0.92)	0.008	0.83 (0.66-1.05)	0.123	0.72 (0.52-0.99)	0.042	0.82 (0.59-1.12)	0.213
Tumor size (cm) (≤ 5/> 5)	0.57 (0.46-0.72)	< 0.001	0.74 (0.57-0.95)	0.019	0.6 (0.43-0.82)	0.002	0.66 (0.48-0.93)	0.017
Microvascular invasion (yes/no)	1.55 (1.21-1.99)	< 0.001	1.19 (0.92-1.55)	0.186	1.2 (0.83-1.74)	0.322
Infiltrative growth (yes/no)	1.29 (1.02-1.63)	0.032	1.35 (1.06-1.7)	0.014	1.2 (0.87-1.65)	0.272
Gamma-glutamyl transpeptidase-to-platelet ratio (≤ 0.2/> 0.2)	0.48 (0.36-0.64)	< 0.001	0.52 (0.39-0.69)	< 0.001	0.49 (0.35-0.69)	< 0.001	0.5 (0.36-0.7)	< 0.001

Uni-HR: Hazard ratio for univariable Cox-regression analyses; Multi-HR: Hazard ratio for multivariable Cox-regression analyses.

Table 3 Univariate and multivariate Cox-regression analyses predicting recurrence-free survival before and after propensity score matching

Variables	Before propensity matching				After propensity matching
	Uni-HR (95%CI)	P value	Multi-HR (95%CI)	P value	Uni-HR (95%CI)	P value	Multi-HR (95%CI)	P value
Sex (male/female)	1.32 (1.03-1.69)	0.028	1.19 (0.92-1.54)	0.176	1.09 (0.8-1.49)	0.574
Age (years) (> 50/≤ 50)	1.03 (0.87-1.22)	0.756			0.93 (0.73-1.19)	0.575
Body mass index (> 24/≤ 24)	1.13 (0.94-1.36)	0.185			1 (0.77-1.29)	0.989
Smoking (yes/no)	1.11 (0.93-1.32)	0.244			1.01 (0.78-1.31)	0.93
Drinking (yes/no)	1 (0.84-1.2)	0.972			0.85 (0.64-1.11)	0.23
Diabetes mellitus (yes/no)	1.4 (0.98-2)	0.067			1.22 (0.71-2.1)	0.461
Hypertension (yes/no)	0.81 (0.6-1.09)	0.165			0.83 (0.54-1.26)	0.38
Family cases (yes/no)	0.89 (0.68-1.16)	0.384			0.76 (0.51-1.14)	0.192
Liver flukes (yes/no)	1.14 (0.93-1.4)	0.204			1.01 (0.74-1.38)	0.945
Cirrhosis (yes/no)	1.27 (1.08-1.5)	0.005	1.25 (1.05-1.49)	0.012	1.3 (1.03-1.65)	0.03	1.33 (1.04-1.68)	0.021
Child-Pugh (B/A)	1.08 (0.54-2.18)	0.823			1.01 (0.32-3.14)	0.99
Barcelona Clinic Liver Cancer stage (A/0)	1.4 (1.09-1.8)	0.008	1.14 (0.87-1.49)	0.348	1.39 (0.98-1.97)	0.061
Total bilirubin (μmol/L) (> 20.5/≤ 20.5)	0.87 (0.67-1.13)	0.292			0.85 (0.6-1.22)	0.386
Albumin (g/L) (> 40/≤ 40)	1.36 (1.15-1.61)	< 0.001	1.17 (0.98-1.4)	0.084	1.21 (0.96-1.54)	0.112
Alpha-fetoprotein (ng/mL) (≥ 200/< 200)	1.31 (1.1-1.55)	0.002	1.29 (1.08-1.54)	0.005	1.22 (0.96-1.55)	0.111
Hepatitis B virus DNA (IU/mL) (> 1000/≤ 1000)	0.8 (0.68-0.95)	0.009	0.9 (0.76-1.06)	0.214	0.76 (0.6-0.96)	0.023	0.8 (0.63-1.02)	0.067
Tumor size (cm) (≤ 5/> 5)	0.6 (0.51-0.71)	< 0.001	0.67 (0.55-0.81)	< 0.001	0.79 (0.62-1.02)	0.07
Microvascular invasion (yes/no)	1.4 (1.16-1.68)	< 0.001	1.1 (0.9-1.33)	0.359	1.18 (0.9-1.56)	0.233
Infiltrative growth (yes/no)	1.24 (1.05-1.47)	0.013	1.28 (1.08-1.53)	0.005	1.24 (0.97-1.57)	0.082
Gamma-glutamyl transpeptidase-to-platelet ratio (≤ 0.2/> 0.2)	0.49 (0.4-0.6)	< 0.001	0.53 (0.43-0.65)	< 0.001	0.56 (0.44-0.71)	< 0.001	0.57 (0.44-0.73)	< 0.001

Uni-HR: Hazard ratio for univariable Cox-regression analyses; Multi-HR: Hazard ratio for multivariable Cox-regression analyses.

Table 4 Stratified analysis between gamma-glutamyl transpeptidase-to-platelet ratio levels and prognosis in the solitary hepatitis B virus-related hepatocellular carcinoma

Variables	Before propensity matching				After propensity matching
	OS-HR (95%CI)	P value	RFS-HR (95%CI)	P value	OS-HR (95%CI)	P value	RFS-HR (95%CI)	P value
As continuous	1.12 (1.04-1.20)	0.002	1.11 (1.06-1.17)	< 0.001	1.29 (1.18-1.42)	< 0.001	1.20 (1.11-1.31)	< 0.001
By GPR cut-off
GPR ≤ 0.2
GPR > 0.2	2.07 (1.56-2.74)	< 0.001	2.05 (1.68-2.51)	< 0.001	2.04 (1.46-2.84)	< 0.001	1.79 (1.40-2.28)	< 0.001
By GPR tercile
Bottom (≤ 0.2)
Middle (> 0.2, ≤ 0.6)	1.81 (1.35-2.44)	< 0.001	1.85 (1.50-2.29)	< 0.001	1.52 (1.08-2.14)	0.017	1.69 (1.25-2.17)	< 0.001
Top (> 0.6)	2.74 (1.98-3.81)	< 0.001	2.60 (2.04-3.31)	< 0.001	2.33 (1.60-3.39)	< 0.001	2.35 (1.77-3.13)	< 0.001
P for trend1	< 0.001		< 0.001		< 0.001		< 0.001
By interquartile
Q1
Q2	1.42 (0.98-2.06)	0.061	1.43 (1.10-1.86)	< 0.001	0.75 (0.43-1.28)	0.288	0.88 (0.60-1.29)	0.514
Q3	1.72 (1.20-2.46)	0.003	1.74 (1.35-2.24)	< 0.001	1.45 (0.90-2.34)	0.125	1.58 (1.12-2.23)	0.009
Q4	2.34 (1.66-3.29)	< 0.001	2.29 (1.79-2.93)	< 0.001	2.08 (1.33-3.24)	0.001	1.79 (1.27-2.51)	0.001
P for trend1	< 0.001		< 0.001		< 0.001		< 0.001

¹Test for trend based on variable containing median value for each classification.

HR: Hazard ratio; OS: Overall survival; RFS: Recurrence-free survival; GPR: Gamma-glutamyl transpeptidase-to-platelet ratio.