Preoperative gamma-glutamyltransferase to lymphocyte ratio predicts long-term outcomes in intrahepatic cholangiocarcinoma patients following hepatic resection

doi:10.3748/wjg.v26.i13.1501

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World Journal of Gastroenterology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Apr 7, 2020; 26(13): 1501-1512
Published online Apr 7, 2020. doi: 10.3748/wjg.v26.i13.1501

Table 1 Correlation between gamma-glutamyltransferase to lymphocyte ratio and clinicopathological characteristics in intrahepatic cholangiocarcinoma

Variables	Derivation		P value	Validation		P value
Variables	GLR ≤ 33.7	GLR > 33.7	P value	GLR ≤ 33.7	GLR > 33.7	P value
Total patients	107	157		97	166
Age, yr	57.96 (11.48)	57.80 (10.35)	0.902	56.97 (10.69)	56.48 (10.56)	0.716
Male gender, n (%)	42 (39.3)	85 (54.1)	0.024^a	38 (39.2)	89 (53.6)	0.030^a
HBsAg, n (%)	36 (33.6)	37 (23.6)	0.073	31 (32.3)	47 (28.5)	0.575
Hepatolithiasis, n (%)	14 (13.1)	27 (17.2)	0.396	15 (15.5)	32 (19.3)	0.511
Child-Pugh grade B, n (%)	3 (2.8)	8 (5.1)	0.533	2 (2.1)	11 (6.6)	0.141
Ascites, n (%)	6 (5.6)	21 (13.4)	0.061	4 (4.1)	19 (11.4)	0.068
CA-199 < 22, n (%)	38 (36.5)	42 (27.5)	0.005^a	29 (31.2)	40 (24.2)	0.043^a
Tumor size, cm	5.14 (2.29)	6.51 (2.78)	< 0.001^a	5.40 (2.22)	6.36 (2.97)	0.007^a
Solitary tumor, n (%)	89 (83.2)	102 (65.0)	0.001^a	67 (69.1)	113 (68.1)	0.895
Well tumor differentiation, n (%)	6 (5.6)	4 (2.5)	0.331	5 (5.2)	7 (4.2)	0.767
Macrovascular invasion, n (%)	17 (15.9)	45 (28.7)	0.011^a	8 (8.2)	53 (31.9)	< 0.001^a
Microvascular invasion, n (%)	6 (5.6)	23 (14.6)	0.026^a	7 (7.2)	17 (10.2)	0.514
Liver capsule invasion, n (%)	67 (62.6)	107 (68.2)	0.362	64 (66.0)	97 (58.4)	0.248
Node-positive, n (%)	16 (15.0)	48 (30.6)	0.005^a	18 (18.6)	47 (28.3)	0.107
Perineural invasion, n (%)	9 (8.4)	27 (17.2)	0.044^a	8 (8.2)	35 (21.1)	0.009^a
Cirrhosis, n (%)	27 (25.2)	53 (33.8)	0.174	19 (19.6)	46 (27.7)	0.182
TNM stage, n (%)			0.002^a			0.107
IA	23 (21.5)	12 (7.6)		13 (13.4)	15 (9.0)
IB	6 (5.6)	12 (7.6)		6 (6.2)	13 (7.8)
II	6 (5.6)	13 (8.3)		10 (10.3)	26 (15.7)
IIIA	55 (51.4)	72 (45.9)		50 (51.5)	64 (38.6)
IIIB	17 (15.9)	48 (30.6)		18 (18.6)	48 (28.9)
BCLC stage, n (%)			< 0.001^a			< 0.001^a
0	6 (5.6)	9 (5.7)		3 (3.1)	5 (3.0)
A	44 (41.1)	25 (15.9)		34 (35.1)	38 (22.9)
B	40 (37.4)	78 (49.7)		52 (53.6)	70 (42.2)
C	17 (15.9)	45 (28.7)		8 (8.2)	53 (31.9)

^aP < 0.05. HBV: Hepatitis B virus; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; BCLC: BARCELONA Clinic Liver Cancer; GLR: Gamma-glutamyltransferase to lymphocyte ratio; ICC: Intrahepatic cholangiocarcinoma; HR: Hazard ratio; CI: Confidence interval.

Table 2 Univariate analysis in the derivation cohort

Variables	Overall survival			Recurrence-free survival
Variables	HR	95%CI	P value	HR	95%CI	P value
Age	1.002	0.987-1.017	0.819	0.998	0.985-1.011	0.763
Gender, F/M	0.752	0.546-1.035	0.080^a	0.846	0.633-1.132	0.262
HBsAg	1.210	0.853-1.717	0.285	1.274	0.924-1.756	0.139
Hepatolithiasis	1.593	1.061-2.393	0.025^a	1.176	0.785-1.761	0.433
Child-Pugh grade, A /B	0.614	0.323-1.167	0.136	0.732	0.381-1.367	0.317
Ascites	1.639	1.011-2.658	0.045^a	1.532	0.988-2.376	0.056^a
CA-199 (≥ 22/< 22)	0.953	0.926-0.981	0.001^a	1.546	1.259-1.899	< 0.001^a
Tumor size	1.075	1.012-1.141	0.019^a	1.123	1.063-1.187	< 0.001^a
Tumor number, Multiple/Single	1.655	1.172-2.328	0.004^a	1.893	1.388-2.582	< 0.001^a
Tumor differentiation, Moderate-Poor/Well	1.891	0.699-5.115	0.209	3.277	1.045-10.274	0.042^a
Macrovascular invasion	1.371	0.953-1.972	0.089^a	1.277	0.913-1.787	0.153
Microvascular invasion	1.619	1.029-2.548	0.037^a	1.983	1.306-3.012	0.001^a
Liver capsule invasion	0.815	0.586-1.134	0.225	1.140	0.833-1.561	0.412
Node-positive	2.846	2.030-3.989	< 0.001^a	2.484	1.810-3.409	< 0.001^a
Perineural invasion	1.737	1.129-2.673	0.012^a	1.245	0.821-1.887	0.302
Cirrhosis	1.526	1.094-2.130	0.013^a	1.182	0.863-1.617	0.297
TNM stage, III/I-II	1.067	0.745-1.529	0.722	1.431	1.010-2.028	0.044^a
BCLC, B-C/0-A	1.295	0.906-1.850	0.156	1.607	1.150-2.246	0.005^a
NLR, > 2.62/≤ 2.62	1.701	1.221-2.371	0.002^a	1.422	1.057-1.912	0.020^a
PLR, > 103/≤ 103	1.366	0.983-1.897	0.063^a	1.360	1.009-1.833	0.043^a
GLR, > 33.7/≤ 33.7	2.316	1.617-3.316	< 0.001^a	1.931	1.413-2.639	< 0.001^a

^aP < 0.10. M: male; F: Female; HBV: Hepatitis B virus; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; BCLC: Barcelona Clinic Liver Cancer; NLR: Neutrophil to lymphocyte ratio; PLR: Platelet to lymphocyte ratio; GLR: Gamma-glutamyltransferase to lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval.

Table 3 Univariate analysis in the validation cohort

Variables	Overall survival			Recurrence-free survival
Variables	HR	95%CI	P value	HR	95%CI	P value
Age	0.996	0.981-1.011	0.594	0.990	0.976-1.004	0.148
Gender, F/M	0.907	0.667-1.233	0.534	0.920	0.695-1.218	0.560
HBsAg	1.004	0.717-1.405	0.982	1.110	0.819-1.505	0.500
Hepatolithiasis	1.092	0.744-1.602	0.654	0.799	0.551-1.158	0.236
Child-Pugh grade, A /B	0.852	0.435-1.671	0.642	0.751	0.418-1.350	0.339
Ascites	1.440	0.871-2.382	0.155	1.580	1.004-2.487	0.048^a
CA-199, ≥ 22/< 22	1.744	1.390-2.188	< 0.001^a	1.402	1.140-1.722	0.001^a
Tumor size	1.054	0.997-1.115	0.064^a	1.084	1.030-1.141	0.002^a
Tumor number, Multiple/Single	1.845	1.344-2.531	< 0.001^a	1.874	1.397-2.513	< 0.001^a
Tumor differentiation, Moderate-Poor/Well	13.449	1.881-96.150	0.010	6.053	1.930-18.982	0.002^a
Macrovascular invasion	1.050	0.730-1.511	0.792	1.009	0.718-1.418	0.959
Microvascular invasion	1.995	1.228-3.242	0.005^a	2.023	1.290-3.172	0.002^a
Liver capsule invasion	1.553	1.118-2.159	0.009^a	1.280	0.955-1.716	0.099^a
Node-positive	2.009	1.438-2.808	< 0.001^a	1.525	1.115-2.085	0.008^a
Perineural invasion	1.366	0.906-2.059	0.136	1.262	0.867-1.838	0.225
Cirrhosis	0.984	0.686-1.412	0.932	1.054	0.762-1.459	0.749
TNM stage, III/I-II	1.774	1.242-2.533	0.002^a	1.413	1.035-1.929	0.029
BCLC, B-C/0-A	1.619	1.136-2.308	0.008^a	1.849	1.335-2.562	< 0.001^a
NLR, > 2.62/≤ 2.62	1.649	1.202-2.261	0.002^a	1.635	1.226-2.180	0.001^a
PLR, > 103/≤ 103	1.417	1.036-1.938	0.029^a	1.065	0.803-1.414	0.661
GLR, > 33.7/≤ 33.7	1.826	1.300-2.565	0.001^a	1.780	1.315-2.408	< 0.001^a

^aP < 0.10. M: Male; F: Female; HBV: Hepatitis B virus; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; BCLC: Barcelona Clinic Liver Cancer; NLR: Neutrophil to lymphocyte ratio; PLR: Platelet to lymphocyte ratio; GLR: Gamma-glutamyltransferase to lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval.

Table 4 Multivariate analysis of prognostic factors for overall survival and recurrence-free survival

OS	Derivation cohort (n = 264)			Validation cohort (n = 263)
OS	HR	95%CI	P value	HR	95%CI	P value
Gender, F/M	0.847	0.58-1.216	0.367	-
Hepatolithiasis	1.073	0.677-1.699	0.765	-
Child-Pugh grade, A /B	0.775	0.38-1.583	0.485	-
Ascites	0.758	0.428-1.339	0.340	0.640	0.376-1.090	0.100
CA-199, ≥ 22/< 22	1.731	1.331-2.252	< 0.001^a	1.612	1.252-2.075	< 0.001^a
Tumor size	1.053	0.967-1.146	0.234	0.931	0.857-1.011	0.088
Tumor number, Multiple/Single	1.662	1.086-2.543	0.019^a	1.677	1.189-2.366	0.003^a
Tumor differentiation, Moderate-Poor/Well	-			7.927	1.083-58.02	0.042^a
Macrovascular invasion	1.199	0.781-1.843	0.407	-
Microvascular invasion	1.082	0.635-1.842	0.773	1.349	0.801-2.274	0.261
Liver capsule invasion	-			1.036	0.533-2.013	0.917
Node- positive	2.038	1.365-3.042	< 0.001^a	1.269	0.835-1.928	0.265
Perineural invasion	1.252	0.773-1.116	0.169	0.973	0.591-1.603	0.914
Cirrhosis	1.589	1.074-2.351	0.020^a	-
TNM stage, III/I-II	-			1.294	0.607-2.761	0.505
BCLC, B-C/0-A	0.627	0.364-1.078	0.091	1.307	0.813-2.101	0.269
NLR, > 2.62/≤ 2.62	1.357	0.912-2.017	0.132	1.287	0.897-1.846	0.170
PLR, > 103/≤ 103	1.141	0.776-1.679	0.502	1.094	0.778-1.539	0.604
GLR, > 33.7/≤ 33.7	1.620	1.066-2.462	0.024^a	1.466	1.033-2.142	0.048^a
RFS
Age	-			0.991	0.976-1.006	0.236
HBsAg	1.367	0.974-1.919	0.071	-
Ascites	0.763	0.473-1.230	0.266	0.621	0.382-1.010	0.055
CA-199, ≥ 22/< 22	1.406	1.128-1.752	0.002^a	1.319	1.050-1.656	0.017^a
Tumor size	1.073	0.994-1.158	0.072	0.975	0.906-1.050	0.501
Tumor number, Multiple/Single	1.434	0.998-2.060	0.051	1.613	1.172-2.219	0.003^a
Tumor differentiation, Moderate-Poor/Well	2.068	0.635-6.734	0.228	3.617	1.114-11.741	0.032^a
Macrovascular invasion	1.149	0.785-1.682	0.475	-
Microvascular invasion	1.643	1.031-2.618	0.037^a	1.607	0.986-2.618	0.057
Liver capsule invasion	-			0.778	0.428-1.417	0.413
Node-positive	1.859	1.272-2.716	0.001^a	0.972	0.664-1.421	0.882
TNM stage, III/I-II	0.892	0.559-1.328	0.572	1.524	0.778-2.988	0.220
BCLC, B-C/0-A	0.784	0.480-1.280	0.331	1.339	0.859-2.087	0.198
NLR, > 2.62/≤ 2.62	1.128	0.811-1.571	0.474	1.352	0.967-1.891	0.077
PLR, > 103/≤ 103	1.125	0.809-1.565	0.483	0.805	0.589-1.100	0.173
GLR, > 33.7/≤ 33.7	1.471	1.029-2.103	0.034^a	1.480	1.057-2.070	0.022^a

^aP < 0.05. OS: Overall survival; RFS: Recurrence-free survival; HBV: Hepatitis B virus; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; BCLC: Barcelona Clinic Liver Cancer; GLR: Gamma-glutamyltransferase to lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval.

Citation: Wang JJ, Li H, Li JX, Xu L, Wu H, Zeng Y. Preoperative gamma-glutamyltransferase to lymphocyte ratio predicts long-term outcomes in intrahepatic cholangiocarcinoma patients following hepatic resection. World J Gastroenterol 2020; 26(13): 1501-1512
URL: https://www.wjgnet.com/1007-9327/full/v26/i13/1501.htm
DOI: https://dx.doi.org/10.3748/wjg.v26.i13.1501