Prognostic roles of preoperative &alpha;-fetoprotein and des-&gamma;-carboxy prothrombin in hepatocellular carcinoma patients

doi:10.3748/wjg.v21.i16.4933

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World Journal of Gastroenterology

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World J Gastroenterol. Apr 28, 2015; 21(16): 4933-4945
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4933

Table 1 Characteristics of hepatocellular carcinoma patients with hepatitis B virus infection

Variables	All patients (n = 105)	LL group (n = 55)	HL group (n = 34)	HH group (n = 16)	P value
Age (yr)	62 (57-68)	62 (59-66)	64 (56-70)	63 (56-70)	0.962
Sex, male/female	90/15	48/7	29/5	13/3	0.829
Body mass index (kg/m²)	23.7 ± 3.1	24.0 ± 2.6	23.5 ± 3.3	23.1 ± 4.3	0.691
Open/pure lap/lap-assisted	83/8/14	43/6/6	29/1/4	11/1/4	0.390
Hr
0/S/1/2/3	50/25/14/14/2	34/13/6/2/0	14/10/4/4/2	2/2/4/8/0	< 0.001
Preoperative laboratory values
Aspartate transaminase (U/L)	31 (22-46)	31 (22-41)	30 (25-48)	43 (24-62)	0.153
Alanine transaminase (U/L)	29 (20-39)	32 (17-42)	27 (21-42)	27 (19-52)	0.978
Platelets (× 10⁴/μL)	16.6 ± 13.3	16.4 ± 12.7	16.2 ± 16.2	18.0 ± 8.6	0.168
Serum ALB (g/dL)	3.95 ± 0.46	3.99 ± 0.46	3.87 ± 0.43	3.98 ± 0.53	0.334
PT (%)	93.3 ± 12.2	95.5 ± 11.1	90.3 ± 14.1	92.2 ± 10.6	0.062
Serum TBIL (mg/dL)	0.79 ± 0.44	0.80 ± 0.45	0.85 ± 0.49	0.65 ± 0.24	0.681
ICGR15	9.6 (5.7-14.9)	9.4 (5.9-14.0)	12.5 (5.7-22.5)	8.5 (5.0-14.6)	0.334
AFP (ng/mL)	24.2 (3.8-165.0)	5.2 (2.4-31.1)	45.0 (5.1-246.5)	1950 (753.5-2827.0)	< 0.001
DCP (mAU/mL)	38 (20-364)	22 (15-28)	399 (90-1,667)	4460 (223-34373)	< 0.001
Intraoperative data
Blood loss (mL)	400 (130-660)	360 (110-560)	435 (100-1,040)	880 (130-1330)	0.042
Surgical duration (min)	332 (243-411)	313 (236-370)	361 (243-450)	432 (270-604)	0.020
Blood transfusion
RCC: yes/no (%)	21/84 (20.0%)	4/51 (7.2%)	10/24 (29.4%)	7/9 (43.8%)	0.001
Pathological results
Tumor size (cm)	4.27 ± 3.21	3.26 ± 2.56	4.97 ± 2.71	6.24 ± 4.77	< 0.001
Multiple tumors: yes/no (%)	39/66 (37.1%)	19/36 (34.5%)	15/19 (44.1%)	5/11 (31.3%)	0.575
Vascular invasion: yes/no (%)	34/71 (32.4%)	10/45 (18.2%)	14/20 (41.1%)	10/6 (62.5%)	0.002
Remnant liver: NL/CH/LC	13/47/41	6/23/26	3/17/14	4/7/5	0.464
Histological tumor differentiation
Well/moderately/poorly	14/63/28	11/35/9	3/18/13	0/10/6	0.048
Recurrence within 2 yr after liver resection
Yes/no (%)	50/55 (47.6%)

Data are presented as medians (25^th-75^th percentile range) for skewed distribution and mean ± SD for normal distribution. LL group: AFP values < 529.8 ng/mL and DCP values < 60 mAU/mL; HL group: AFP values > 529.8 ng/mL or DCP values > 60 mAU/mL; HH group: AFP values > 529.8 ng/mL and DCP values > 60 mAU/mL; Open group: Open laparotomy hepatectomy group; Lap group: laparoscopic hepatectomy group; Pure Lap: Pure laparoscopic hepatectomy; Lap-assisted: Laparoscopy-assisted hepatectomy. Hr0: Partial hepatectomy; HrS: Subsegmentectomy; Hr1: Sectionectomy; Hr2: Bisegmentectomy; Hr3: Trisegmentectomy; ALB: Albumin; PT: Prothrombin; TBIL: Total bilirubin; ICGR15: Indocyanine green retention rate at 15 min; AFP: Alpha-fetoprotein; DCP: Des-γ-carboxy prothrombin.

Table 2 Univariate and multivariate analyses of factors associated with tumor recurrence in patients with hepatitis B virus infection

Variables	Univariate analysis			Multivariate analysis
Variables	HR	95%CI	P value	HR	95%CI	P value
Age	0.977	0.952-1.003	0.086
Sex, male	1.077	0.512-2.264	0.843
Preoperative laboratory values
Aspartate transaminase	1.008	1.003-1.013	0.001¹	1.001	0.993-1.010	0.778
Alanine transaminase	0.999	0.989-1.009	0.811
Platelets	1.001	0.979-1.024	0.929
Serum ALB	0.648	0.367-1.142	0.134
PT	0.974	0.953-0.996	0.021¹	0.976	0.946-1.007	0.124
Serum TBIL	2.305	1.346-3.947	0.002¹	4.068	1.586-10.436	0.004¹
ICGR₁₅	1.033	1.008-1.059	0.011¹	0.967	0.919-1.018	0.967
Tumor markers
HH group	3.235	1.673-6.257	< 0.001¹	2.464	1.086-5.587	0.031¹
HL group	2.042	1.164-3.583	0.013¹	1.083	0.497-2.360	0.841
Intraoperative data
Blood loss	1.001	1.000-1.001	0.002¹	1.000	1.000-1.001	0.416
Surgical duration	1.002	1.000-1.004	0.003¹	1.000	0.997-1.003	0.868
Pathologic results
Tumor size	1.148	1.068-1.234	< 0.001¹	1.182	1.059-1.318	0.003¹
Multiple tumors	1.363	1.152-1.612	< 0.001¹	1.336	0.955-1.869	0.091
Vascular invasion	2.088	1.261-3.458	0.004¹	2.624	1.408-4.892	0.002¹

¹Represents statistical significance. HH group: Alpha-fetoprotein values > 529.8 ng/mL and des-gamma-carboxy prothrombin values > 60 mAU/mL; HL group: Alpha-fetoprotein values > 529.8 ng/mL or des-gamma-carboxy prothrombin values > 60 mAU/mL. ALB: Albumin; PT: Prothrombin; TBIL: Total bilirubin; ICGR15: Indocyanine green retention rate at 15 min.

Table 3 Univariate and multivariate analyses of factors associated with poor overall survival in patients with hepatitis B virus infection

Variables	Univariate analysis			Multivariate analysis
Variables	HR	95%CI	P value	HR	95%CI	P value
Age	0.996	0.964-1.028	0.797
Sex, male	1.440	0.511-4.056	0.490
Preoperative laboratory values
Aspartate transaminase	1.008	1.002-1.014	0.012¹	1.004	0.992-1.016	0.518
Alanine transaminase	0.992	0.976-1.007	0.296
Platelets	1.015	0.994-1.035	0.158
Serum ALB	0.469	0.234-0.939	0.033
PT	0.975	0.950-1.000	0.051
Serum TBIL	2.249	1.125-4.495	0.022¹	1.584	0.447-5.613	0.476
ICGR₁₅	1.056	1.025-1.087	< 0.001¹	1.040	0.976-1.108	0.229
Tumor markers
HH group	2.985	1.259-7.075	0.013¹	2.274	0.698-7.403	0.173
HL group	2.112	1.054-4.232	0.035¹	1.025	0.390-2.693	0.960
Intraoperative data
Blood loss	1.001	1.001-1.001	< 0.001¹	1.000	1.000-1.001	0.391
Surgical duration	1.004	1.001-1.008	0.005¹	1.002	0.996-1.007	0.534
Pathologic results
Tumor size	1.239	1.133-1.356	< 0.001¹	1.127	0.969-1.310	0.122
Multiple tumors	1.385	1.121-1.711	0.002¹	1.200	0.813-1.772	0.358
Vascular invasion	2.491	1.335-4.647	0.004¹	3.173	1.352-7.447	0.008¹

Table 4 Characteristics of hepatocellular carcinoma patients with hepatitis C virus infection

Variables	All patients (n = 100)	LL group (n = 34)	HL group (n = 39)	HH group (n = 27)	P value
Age (yr)	71 (62-77)	72 (64-77)	70 (62-75)	70 (65-77)	0.766
Sex, male/female	82/18	22/12	29/10	16/11	0.413
Body mass index	23.6 ± 3.6	23.6 ± 2.9	23.8 ± 3.8	23.4 ± 4.1	0.737
Open/Pure Lap/Lap-assisted	77/12/11	26/3/5	27/8/4	24/1/2	0.218
Hr
0/S/1/2/3	57/27/11/2/3	23/8/3/0/0	21/10/5/1/2	13/9/3/1/1	0.784
Preoperative laboratory values
Aspartate transaminase (U/L)	47 (30-64)	41 (23-56)	48 (35-67)	53 (47-71)	0.101
Alanine transaminase (U/L)	38 (26-57)	33 (21-53)	41 (28-57)	42 (29-62)	0.496
Platelets (× 10⁴/μL)	13.5 ± 6.8	13.9 ± 4.7	13.9 ± 9.2	12.5 ± 4.4	0.804
Serum ALB (g/dL)	3.76 ± 0.39	3.94 ± 0.40	3.67 ± 0.35	3.67 ± 0.38	0.006¹
PT (%)	89.8 ± 13.4	92.5 ± 11.4	87.8 ± 15.0	89.2 ± 13.5	0.254
Serum TBIL (mg/dL)	0.78 ± 0.34	0.74 ± 0.32	0.79 ± 0.33	0.81 ± 0.39	0.777
ICGR15	14.2 (8.4-18.5)	12.1 (8.1-15.4)	14.7 (8.4-21.5)	15.6 (13.0-24.6)	0.163
AFP (ng/mL)	18.6 (5.6-134.0)	5.3 (3.8-11.0)	21.1 (6.9-99.2)	299.7 (68.1-1046.0)	< 0.001¹
DCP (mAU/mL)	45 (21-244)	22 (15-35)	37 (23-134)	429 (124-1902)	< 0.001¹
Intraoperative data
Blood loss (mL)	330 (20-650)	263 (70-500)	230 (20-500)	535 (300-1270)	0.006¹
Surgical duration (min)	304 (230-377)	303 (175-377)	296 (230-352)	345 (282-475)	0.040¹
Blood transfusion
RCC: yes/no (%)	12/88 (12.0%)	3/31 (8.8%)	2/37 (5.1%)	7/20 (25.9%)	0.030¹
Pathologic results
Tumor size (cm)	3.51 ± 2.48	2.84 ± 1.23	3.26 ± 2.31	4.72 ± 3.39	0.008¹
Multiple tumor: yes/no (%)	36/64 (36.0%)	8/26 (23.5%)	17/22 (43.6%)	11/16 (40.7%)	0.171
Vascular invasion: yes/no (%)	30/70 (30.0%)	5/29 (14.7%)	12/27 (30.8%)	13/14 (48.1%)	0.018¹
Remnant liver: NL/CH/LC	5/37/58	2/18/14	2027/10/2	2017/9/1	0.161
Histological tumor differentiation
Well/Moderately/Poorly	17/63/20	7/23/4	8/24/7	2/16/9	0.213
Recurrence within 2 yr after hepatectomy
Yes/no (%)	51/49 (51.0%)

¹Represents statistically significance. Data are presented as medians (25^th-75^th percentile range) for skewed distribution and mean ± SD for normal distribution. LL group: AFP values < 21.0 ng/mL and DCP values < 67 mAU/mL; HL group: AFP values < 21.0 ng/mL or DCP values < 67 mAU/mLF; HH group: AFP values < 21.0 ng/mL and DCP values < 67 mAU/mL; Open group: Open laparotomy group; Lap group: Laparoscopic hepatectomy group; Pure Lap: Pure laparoscopic hepatectomy; Lap-assisted, laparoscopy-assisted hepatectomy; Hr0: Partial hepatectomy; HrS: Sub-segmentectomy; Hr1: Sectionectomy; Hr2: Bisegmentectomy; Hr3: Trisegmentectomy. ALB: albumin; PT: prothrombin; TBIL: total bilirubin; ICGR15: indocyanine green retention rate at 15 min; AFP: Alpha-fetoprotein; DCP: Des-γ-carboxy prothrombin.

Table 5 Univariate and multivariate analyses of factors associated with tumor recurrence in patients with hepatitis C virus infection

Variables	Univariate analysis			Multivariate analysis
Variables	HR	95%CI	P value	HR	95%CI	P value
Age	1.001	0.972-1.031	0.950
Sex, male	1.455	0.823-2.570	0.197
Preoperative laboratory values
Aspartate transaminase	1.005	0.999-1.011	0.134
Alanine transaminase	1.003	0.966-1.010	0.412
Platelets	1.015	0.983-1.049	0.363
Serum ALB	0.569	0.297-1.092	0.090
PT	0.999	0.980-1.019	0.943
Serum TBIL	1.281	0.610-2.692	0.513
ICGR15	1.049	1.017-1.081	0.002¹	1.069	1.032-1.108	< 0.001¹
Tumor markers
HH group	4.427	2.238-8.760	< 0.001¹	5.098	2.165-12.005	< 0.001¹
HL group	2.210	1.166-4.189	0.015¹	2.325	1.077-5.018	0.032¹
Intraoperative data
Blood loss	1.001	1.000-1.001	< 0.001¹	1.000	0.999-1.000	0.292
Surgical duration	1.003	1.002-1.004	< 0.001¹	1.002	0.998-1.006	0.129
Pathologic results
Tumor size	1.290	1.178-1.413	< 0.001¹	1.160	1.033-1.302	0.012¹
Multiple tumors	1.264	1.073-1.487	0.005¹	1.264	1.041-1.534	0.018¹
Vascular invasion	2.454	1.479-4.071	0.001¹	1.597	0.890-2.867	0.117

¹Represents statistical significance. HH group: Alpha-fetoprotein values > 21.0 ng/mL and des-gamma-carboxy prothrombin values > 67 mAU/mL; HL group: Alpha-fetoprotein values > 21.0 ng/mL or des-gamma-carboxy prothrombin values > 67 mAU/mL. ALB: Albumin; PT: Prothrombin; TBIL: Total bilirubin; ICGR15: Indocyanine green retention rate at 15 min.

Table 6 Univariate and multivariate analyses of factors associated with poor overall survival in patients with hepatitis C virus infection

Variables	Univariate analysis			Multivariate analysis
Variables	HR	95%CI	P value	HR	95%CI	P value
Age	1.025	0.987-1.065	0.195
Sex, male	1.328	0.668-2.642	0.418
Preoperative laboratory values
Aspartate transaminase	1.006	0.999-1.013	0.106
Alanine transaminase	1.001	0.992-1.009	0.849
Platelets	1.036	0.995-1.077	0.084
Serum ALB	0.246	0.114-0.531	< 0.001¹	0.611	0.219-1.706	0.347
PT	0.994	0.971-1.018	0.643
Serum TBIL	1.206	0.523-2.780	0.660
ICGR15	1.054	1.021-1.087	0.001¹	1.042	1.001-1.084	0.047¹
Tumor markers
HH group	4.562	2.031-10.248	< 0.001¹	4.018	1.424-11.337	0.009¹
HL group	2.049	0.911-4.609	0.083	2.209	0.829-5.885	0.113
Intraoperative data
Blood loss	1.001	1.000-1.001	< 0.001¹	1.000	0.999-1.001	0.727
Surgical duration	1.003	1.002-1.004	< 0.001¹	1.002	0.998-1.005	0.414
Pathologic results
Tumor size	1.285	1.162-1.421	< 0.001¹	1.081	0.946-1.235	0.255
Multiple tumors	1.204	1.021-1.420	0.027¹	1.257	1.025-1.542	0.028¹
Vascular invasion	2.223	1.221-4.045	0.009¹	1.089	0.490-2.421	0.835

Citation: Meguro M, Mizuguchi T, Nishidate T, Okita K, Ishii M, Ota S, Ueki T, Akizuki E, Hirata K. Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients. World J Gastroenterol 2015; 21(16): 4933-4945
URL: https://www.wjgnet.com/1007-9327/full/v21/i16/4933.htm
DOI: https://dx.doi.org/10.3748/wjg.v21.i16.4933