Heparin is an effective treatment for preventing liver failure after hepatectomy

Table 1 Baseline of patients between two groups

	Before matching			After matching
	Heparin-free group (n = 421)	Heparin group (n = 967)	P value	Heparin-free group (n = 213)	Heparin group (n = 213)	P value
Gender (male/female)	243/178	507/409	0.069	133/80	122/91	0.277
Age (yr)	56.70 ± 14.88	58.10 ± 14.46	0.100	56.00 ± 14.90	57.58 ± 15.58	0.274
Height (cm)	169.20 ± 8.82	168.30 ± 8.57	0.080	170.00 ± 9.09	169.50 ± 9.10	0.551
Weight (kg)	68.10 ± 14.55	66.30 ± 13.28	0.820	69.00 ± 14.36	68.81 ± 14.03	0.870
Malignant tumor (Yes/No)	119 (28.3%)	421 (43.5%)	0.000	55 (25.8%)	74 (34.7%)	0.045
Laparoscopic (Yes/No)	379 (90.0%)	802 (82.9%)	0.001	206 (96.7%)	198 (93%)	0.080
Smoking (Yes/No)	50 (11.9%)	100 (10.3%)	0.397	38 (17.8%)	39 (18.3%)	0.900
Ethnicity (white/not white)	296 (70.3%)	625 (64.6%)	0.040	146 (68.5%)	161 (75.6%)	0.105
Hypertension (Yes/No)	190 (45.1%)	231 (54.9%)	0.787	94 (44.1%)	97 (45.5%)	0.770
PVTT (Yes/No)	21 (5.0%)	37 (3.8%)	0.320	12 (5.6%)	14 (6.6%)	0.686
Diabetes (Yes/No)	5 (1.2%)	61 (6.3%)	0.000	1 (0.5%)	2 (0.9%)	0.562
Cirrhosis (Yes/No)	81 (19.2%)	137 (14.2%)	0.017	56 (26.3%)	50 (23.5%)	0.501
Portal hypertension (Yes/No)	61 (14.5%)	75 (7.8%)	0.000	40 (18.8%)	25 (11.7%)	0.043
COPD (Yes/No)	25 (5.9%)	45 (4.7%)	0.315	14 (6.6%)	10 (4.7%)	0.401
CKD (Yes/No)	39 (9.3%)	40 (4.1%)	0.000	23 (10.8%)	19 (8.9%)	0.516
Transfusion (Yes/No)	83 (19.7%)	92 (9.5%)	0.000	48 (22.5%)	44 (20.7%)	0.638
Laboratory tests
TBIL (mg/mL)	1.1 [0.5, 3.9]	0.9 [0.5, 1.8]	0.002	1.3 [0.5, 4.7]	1.1 [0.6, 3.8]	0.808
AST (U/L)	65 [33, 158]	116 [53, 277]	0.000	68.0 [35.0, 186.5]	89.0 [44.0, 240.0]	0.704
ALT (U/L)	54 [27, 158]	101 [43, 237]	0.000	55.0 [28.0, 168.5]	76.0 [30.0, 210.5]	0.847
LDH (U/L)	263.0 [192.0, 405.0]	272.0 [198.8, 403.5]	0.882	274.0 [199.5, 437.5]	288.0 [201.0, 440.5]	0.487
ALB (g/dL)	3.4 [2.8, 3.8]	3.3 [2.9, 3.7]	0.724	3.4 [2.8, 3.8]	3.2 [2.8, 3.7]	0.639
Cr (mg/dL)	0.9 [0.7, 1.3]	1 [1.0, 1.0]	0.000	0.9 [0.7, 1.4]	1.0 [0.7, 1.4]	0.901
BUN (mg/dL)	16 [11, 28]	14 [11, 20]	0.000	18 [12, 31]	16 [11, 26]	0.629
GFR (mg/dL)	16 [11, 28]	14 [11, 20]	0.000	18 [12, 31]	16 [11, 26]	0.629
WBC (K/μL)	7.3 [5.0, 10.0]	10.0 [7.0, 14.0]	0.000	6.9 [4.7, 9.7]	8.1 [5.0, 12.3]	0.241
PLT (K/μL)	177 [113, 261]	205 [145, 266]	0.001	160.0 [96.0, 235.5]	187.0 [117.5, 245.0]	0.054
INR	1.2 [1.1, 1.6]	1.2 [1.1, 1.4]	0.000	1.2 [1.1, 1.6]	1.3 [1.1, 1.6]	0.408
PT (s)	13.6 [12.1, 18.1]	13.4 [12.2, 15.3]	0.000	13.5 [11.9, 17.8]	14.2 [12.4, 17.3]	0.436
APTT (s)	32 [28.1, 38.7]	29.9 [27.2, 33.9]	0.004	31.6 [28.2, 37.3]	31.0 [27.6, 37.0]	0.202

Variables are shown as “mean (SD)” or “median [IQR]”. Comparisons were made by unpaired student’s test, chi-square test or Mann-Whitney test according to their distribution before propensity score matching (PSM), while paired student’s test, paired chi-square test or Mann-Whitney test are then used after PSM. The bold indicates statistical significance. PVTT: Portal vein tumor thrombus; PSM: Propensity score matching; COPD: Chronic obstructive pulmonary disease; CKD: Chronic kidney disease; RBC: Red blood cell; TBIL: Total bilirubin; AST: Aspartate transaminase; ALT: Alanine transaminase; LDH: Lactate dehydrogenase; ALB: Albumin; Cr: Serum creatinine; BUN: Blood urea nitrogen; GFR: Glomerular filtration rate; WBC: White blood cell; INR: International normalized ratio; PLT: Platelets; PT: Prothrombin time; APTT: Activated partial thromboplastin time.

Table 2 Association between heparin use and clinical outcomes

	Heparin-free group, n (%)	Heparin group, n (%)	OR (95%CI)	P value
Before PSM	n = 421	n = 967
PHLF	66 (15.7)	76 (7.9)	2.180 (1.533, 3.099)	< 0.001
ICU stay	79 (18.8)	129 (13.3)	1.501 (1.104, 2.040)	0.010
Respiratory support	70 (16.6)	72 (7.4)	2.479 (1.745, 3.523)	0.000
CRRT	17 (4)	8 (0.8)	5.044 (2.160, 11.782)	< 0.001
Hypoxemia	39 (9.3)	48 (5.0)	1.955 (1.260, 3.032)	0.003
AKI	40 (9.5)	66 (6.8)	1.433 (0.951, 2.161)	0.086
ICU death	43 (10.2)	43 (4.4)	2.354 (1.543, 3.593)	< 0.001
After PSM	n = 213	n = 213
PHFL	45 (21.1)	28 (13.1)	0.530 (0.303, 0.928)	0.026
ICU stay	49 (23.0)	51 (23.9)	1.722 (0.933, 3.177)	0.082
Respiratory support	43 (20.2)	30 (14.1)	0.502 (0.262, 0.960)	0.037
CRRT	5 (2.3)	4 (1.9)	1.059 (0.249, 4.496)	0.939
Hypoxemia	23 (10.8)	23 (10.8)	1.181 (0.598, 2.334)	0.631
AKI	22 (10.3)	21 (9.9)	1.017 (0.525, 1.971)	0.960
ICU death	27 (12.7)	24 (11.3)	0.956 (0.469, 1.949)	0.901

Bivariate logistic regression analysis with patients before and post propensity score matching was all applied to investigate variables potentially associated with all secondary clinical outcomes. PSM: Propensity score matching; CRRT: Continuous renal replacement therapy; PHFL: Post-hepatectomy liver failure; AKI: Acute kidney injury.

Table 3 Univariate and multivariate analyses of factors associated with liver failure in matched groups

Factors	B	SE	Wald	OR (95%CI)	P value
Univariate
Heparin	-0.571	0.263	4.703	0.565 [0.337, 0.947]	0.030
Gender	-0.231	0.267	0.749	0.794 [0.470, 1.340]	0.387
Age	-0.009	0.008	1.099	0.991 [0.975, 1.008]	0.294
Height	0.021	0.014	2.055	1.021 [0.992, 1.050]	0.152
Weight	0.026	0.008	9.392	1.026 [1.009, 1.043]	0.002
Malignant tumor	-0.169	0.287	0.347	0.845 [0.482, 1.481]	0.556
Laparoscopic	-0.802	0.468	2.929	0.449 [0.179, 1.123]	0.087
Smoking	0.032	0.252	0.016	1.032 [0.630, 1.691]	0.900
Ethnicity	-0.361	0.274	1.732	0.697 [0.407, 1.193]	0.188
Hypertension	0.085	0.258	0.108	1.088 [0.656, 1.804]	0.743
PVTT	1.207	0.426	8.003	3.343 [1.451, 7.703]	0.005
Diabetes	0.891	1.232	0.523	2.437 [0.218, 27.243]	0.469
Cirrhosis	0.635	0.276	5.319	1.888 [1.100, 3.239]	0.021
Portal hypertension	0.854	0.310	7.579	2.348 [1.279, 4.312]	0.006
COPD	0.389	0.631	0.380	0.678 [0.197, 2.334]	0.537
CKD	0.465	0.388	1.440	1.592 [0.745, 3.404]	0.230
Transfusion	1.565	0.275	32.311	4.783 [2.788, 8.205]	0.000
Laboratory tests
TBIL	0.068	0.017	15.985	1.070 [1.035, 1.107]	0.000
AST	0.000	0.000	2.462	1.000 [1.000, 1.001]	0.117
ALT	0.000	0.000	0.308	1.000 [1.000, 1.001]	0.579
LDH	0.000	0.000	3.279	1.000 [1.000, 1.000]	0.070
ALB	-1.020	0.218	21.989	0.360 [0.235, 0.552]	0.000
Cr	0.054	0.105	0.264	1.056 [0.859, 1.298]	0.608
BUN	-0.005	0.008	0.457	0.995 [0.979, 1.010]	0.499
GFR	-0.005	0.008	0.457	0.995 [0.979, 1.010]	0.499
WBC	0.025	0.016	2.278	1.025 [0.993, 1.058]	0.131
PLT	-0.006	0.002	13.876	0.994 [0.991, 0.997]	0.000
INR	0.529	0.158	11.266	1.697 [1.246, 2.312]	0.001
PT	0.049	0.014	11.643	1.050 [1.021, 1.081]	0.001
APTT	0.010	0.007	1.797	1.010 [0.996, 1.024]	0.180
Multivariate
Heparin	-0.657	0.287	5.236	0.518 [0.295, 0.910]	0.022
PVTT	1.342	0.482	7.734	3.825 [1.486, 9.844]	0.005
Transfusion	1.199	0.297	16.248	3.316 [1.851, 5.940]	< 0.000
TBIL	0.048	0.019	6.558	1.050 [1.011, 1.089]	0.010
ALB	-0.749	0.239	9.815	0.473 [0.296, 0.755]	0.002

The initial screening via univariable logistic regression analysis; all variables with P < 0.1 are considered as potential risk factors, and then allowed in the multivariable analysis with a backward stepwise selection process. Factors with P < 0.05 (the bold) in the final multivariate model means significance. PVTT: Portal vein tumor thrombus; PSM: Propensity score matching; COPD: Chronic obstructive pulmonary disease; CKD: Chronic kidney disease; RBC: Red blood cell; TBIL: Total bilirubin; AST: Aspartate transaminase; ALT: Alanine transaminase; LDH: Lactate dehydrogenase; ALB: Albumin; Cr: Serum creatinine; BUN: Blood urea nitrogen; GFR: Glomerular filtration rate; WBC: White blood cell; INR: International normalized ratio; PLT: Platelets; PT: Prothrombin time; APTT: Activated partial thromboplastin time.