Pre-hepatectomy type IV collagen 7S predicts post-hepatectomy liver failure and recovery

Table 1 Preoperative clinicopathological, liver function, and operative data of the patients

		Overall (n = 215)	No postoperative liver failure (n = 188)	Postoperative liver failure (n = 27)	P value
Age, yr (median)		68	68	72	0.107
Sex	Men	148	125	23	0.073
	Women	67	63	4
Child-Pugh score	5	180	162	18	0.01
	6	27	22	5
	7	7	3	4
	8	1	1	0
Liver tumor	Hepatocellular carcinoma	87	75	12	0.030
	Colorectal metastases	49	46	3
	Hilar cholangiocarcinoma	24	17	7
	Intrahepatic cholangiocarcinoma	20	16	4
	Metastatic liver tumor (other than colorectal cancer)	22	21	1
	Other tumors	13	13	0
Surgery	Partial resection	112	103	9	0.041
	Sectionectomy	23	22	1
	Lobectomy (+extended)	73	58	15
	Three sectionectomy	7	5	2

Table 2 Preoperative levels of liver function parameters in patients with and without postoperative liver failure in univariate analysis

Factor	No postoperative liver failure	Postoperative liver failure	Univariate analysis
	(n = 188)	(n = 27)	OR (95%CI)	P value
Age, yr (median)	68	72		0.095
Sex, male/female	125/63	4/23		0.064
Preoperative biliary drainage	15	7		0.005
Child-Pugh score	5.16 ± 0.45	5.48 ± 0.75	2.505 (1.345-4.665)	0.004
Blood platelet (× 104/μL)	19.5 ± 7.7	16.7 ± 6.6		0.099
Total bilirubin (mg/dL)	0.80 ± 0.33	0.90 ± 0.39		0.099
PT-INR (INR)	1.00 ± 0.12	1.09 ± 0.13	63.56 (2.533-1595.002)	0.012
Albumin (g/dL)	4.03 ± 0.45	3.64 ± 0.54	0.210 (0.091-0.484)	< 0.001
Aspartate aminotransferase (IU/L)	30.9 ± 23.6	40.6 ± 24.8	1.012 (0.999-1.025)	0.071
Alanine aminotransferase (IU/L)	27.3 ± 20.7	32.6 ± 24.2		0.171
Cholinesterase (IU/L)	284.2 ± 82.1	194.6 ± 69.9	0.982 (0.975-0.990)	< 0.001
Total cholesterol (mg/dL)	188.2 ± 39.2	165.8 ± 37.1	0.984 (0.972-0.996)	0.011
ICG-R15 (%)	10.9 ± 9.01	14.8 ± 11.1	1.034 (0.998-1.071)	0.068
Type IV collagen 7S (ng/mL)	5.50 ± 1.91	8.80 ± 3.06	1.601 (1.340-1.914)	< 0.001
Hyaluronic acid (ng/mL)	88.5 ± 100.6	256.5 ± 216.5	1.005 (1.001-1.009)	0.018
ARFITM (v/s)	1.56 ± 0.57	2.01 ± 0.69	2.785 (1.431-5.422)	0.003
CRP (mg/dL)	0.39 ± 1.01	0.82 ± 1.33	1.319 (0.995-1.747)	0.054
Extent of hepatic resection[26]	0.81 ± 0.97	1.37 ± 1.04	1.688 (1.114-2.557)	0.013

PT-INR: Prothrombin time-international normalized ratio; ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.

Table 3 Preoperative liver function parameters in patients with and without post-hepatectomy liver failure in multivariate analysis

Factors	Multivariate analysis
	OR (95%CI)	P value
Sex, male/female	2.802 (0.813-9.653)	0.0513
ICG-R15 (%)	0.998 (0.951-1.047)	0.466
Type IV collagen 7S (ng/mL)	1.543 (1.258-1.892)	< 0.001
ARFITM (v/s)	1.525 (0.673-3.457)	0.156

ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse.

Table 4 Cox proportional hazards analysis to identify predictors of postoperative recovery of liver function to achieve Child-Pugh class A

Factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age, yr (mean)	0.984 (0.972-0.996)	0.007		0.837
Sex, male/female		0.688		0.656
Child-Pugh score	0.577 (0.427-0.780)	< 0.001		0.123
Cholinesterase (IU/L)	1.002 (1.001-1.003)	0.001		0.346
Total cholesterol (mg/dL)	1.004 (1.001-1.007)	0.024		0.932
ICG-R15 (%)	0.980 (0.964-0.997)	0.024		0.756
Type IV collagen 7S (ng/mL)	0.837 (0.784-0.894)	< 0.001	0.779 (0.682-0.890)	< 0.001
Hyaluronic acid (ng/mL)	0.996 (0.994-0.999)	0.003		0.179
ARFITM (v/s)	0.651 (0.490-0.866)	0.003		0.625
CRP (mg/dL)	0.792 (0.669-0.936)	0.006		0.142
Extent of hepatic resection[26]	0.813 (0.707-0.936)	0.004		0.64

ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.

Table 5 Cox proportional hazards analysis to identify predictors of postoperative recovery of liver function to achieve serum total bilirubin < 2 mg/dL

Factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age, yr (mean)		0.275		0.53
Sex, male/female		0.127		0.222
Child-Pugh score	0.749 (0.565-0.994)	< 0.001		0.21
PT-INR (INR)	0.195 (0.47-0.803)	0.024		0.155
Cholinesterase (IU/L)	1.002 (1.001-1.004)	0.003		0.106
ICG-R15 (%)		0.165
Type IV collagen 7S (ng/mL)	0.905 (0.851-0.926)	0.001	0.906 (0.851-0.962)	0.001
Hyaluronic acid (ng/mL)		0.552
ARFITM (v/s)		0.056
CRP (mg/dL)		0.118
Extent of hepatic resection[26]		0.159

PT-INR: Prothrombin time-international normalized ratio; ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.

Table 6 Cox proportional hazards analysis to identify predictors of postoperative recovery of liver function to achieve serum albumin > 2.8 g/dL

Factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age, yr (mean)	0.985 (0.973-0.996)	0.008		0.18
Sex, male/female		0.059		0.457
Child-Pugh score	0.573 (0.424-0.776)	< 0.001		0.611
Cholinesterase (IU/L)	1.002 (1.001-1.003)	0.001		0.39
ICG-R15 (%)	0.979 (0.962-0.996)	0.008		0.983
Type IV collagen 7S (ng/mL)	0.841 (0.787-0.899)	< 0.001	0.759 (0.659-0.875)	< 0.001
Hyaluronic acid (ng/mL)	0.996 (0.994-0.999)	0.004		0.292
ARFITM (v/s)	0.723 (0.545-0.959)	0.024		0.774
CRP (mg/dL)	0.808 (0.685-0.953)	0.011		0.192
Extent of hepatic resection[26]	0.830 (0.722-0.955)	0.009		0.636

ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.

Table 7 Preoperative liver function parameters in post-hepatectomy liver failure and non-post-hepatectomy liver failure patients who did not have hepatitis viruses in univariate analysis

Factors	No postoperative liver failure	Postoperative liver failure	Univariate analysis
	(n = 136)	(n = 22)	OR (95%CI)	P value
Age, yr (mean)	65.3	70.7		0.09
Sex, male/female	87/49	4/18		0.109
Preoperative biliary drainage	9	4		0.045
Child-Pugh score	5.15 ± 0.39	5.59 ± 0.80	3.694 (1.766-7.729)	0.001
Platelets (× 104/μL)	21.1 ± 7.7	17.1 ± 7.0		0.991
Total bilirubin (mg/dL)	0.79 ± 0.33	0.91 ± 0.40		0.111
PT-INR (INR)	0.99 ± 0.13	1.1 ± 0.14	123.581 (2.637-5791.435)	0.014
Albumin (g/dL)	4.03 ± 0.44	3.57 ± 0.60	0.157 (0.059-0.414)	< 0.001
Aspartate aminotransferase (IU/L)	30.8 ± 26.6	41.5 ± 25.9		0.121
Alanine aminotransferase (IU/L)	28.0 ± 22.9	33.6 ± 25.5		0.296
Cholinesterase (IU/L)	293.1 ± 85.1	192.2 ± 67.9	0.979 (0.970-0.988)	< 0.001
Total cholesterol (mg/dL)	192.2 ± 42.2	168.4 ± 40.2	0.985 (0.973-0.998)	0.02
ICG-15 clearance rate (%)	10.3 ± 9.11	15.0 ± 11.8	1.034 (0.998-1.081)	0.064
Type IV collagen 7S (ng/mL)	5.36 ± 1.85	9.15 ± 3.13	1.731 (1.383-2.167)	< 0.001
Hyaluronic acid (ng/mL)	78.7 ± 99.2	261.9 ± 207.3	1.005 (1.004-1.011)	< 0.001
ARFITM (v/s)	1.49 ± 0.53	1.98 ± 0.67	2.785 (1.546-7.887)	0.003
CRP (mg/dL)	0.47 ± 1.14	1.00 ± 1.42		0.056
Extent of hepatic resection[26]	0.90 ± 1.0	1.41 ± 1.05	1.638 (1.037-2.587)	0.034

PT-INR: Prothrombin time-international normalized ratio; ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.

Table 8 Preoperative liver function parameters in post-hepatectomy liver failure and non-post-hepatectomy liver failure patients who did not have hepatitis viruses in multivariate analysis

Factors	Multivariate analysis
	OR (95%CI)	P value
Cholinesterase (IU/L)	0.987 (0.977-0.998)	0.0083
ICG-R15 (%)	0.959 (0.896-1.026)	0.11
Type IV collagen 7S (ng/mL)	1.423 (1.074-1.886)	0.002
Hyaluronic acid (ng/mL)	1.004 (1.000-1.008)	0.021
ARFITM (v/s)	1.144 (0.406-3.220)	0.6

ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse.

Table 9 Preoperative liver function parameters in post-hepatectomy liver failure and non-post-hepatectomy liver failure patients who had jaundice in univariate analysis

Factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age, yr (mean)		0.74		0.817
Sex, male/female		0.105		0.237
Child-Pugh score		0.22
Cholinesterase (IU/L)	0.979 (0.970-0.988)	0.066		0.157
Total cholesterol (mg/dL)		0.652
ICG-R15 (%)		0.371
Type IV collagen 7S (ng/mL)	1.540 (1.036-2.288)	0.033	1.540 (1.036-2.288)	0.033
Hyaluronic acid (ng/mL)		0.187
ARFI TM (v/s)		0.171
CRP (mg/dL)		0.533
Extent of hepatic resection[26]		0.481

ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.

Table 10 Preoperative liver function parameters in post-hepatectomy liver failure and non-post-hepatectomy liver failure patients in univariate and multivariate analyses for 91 patients

Factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Age, yr (mean)		0.083		0.065
Sex, male/female		0.462		0.557
Child-Pugh score		0.347
Platelets (× 104/μL)		0.509
PT-INR (INR)		0.064
Aspartate aminotransferase (IU/L)		0.087
Alanine aminotransferase (IU/L)		0.468
Cholinesterase (IU/L)	0.986 (0.977-0.995)	0.003		0.348
Total cholesterol (mg/dL)		0.128
ICG-R15 (%)		0.643
Type IV collagen 7S (ng/mL)	1.514 (0.784-0.894)	< 0.001	2.178 (0.684-0.890)	0.005
Hyaluronic acid (ng/mL)	1.005 (1.001-1.009)	0.018		0.674
ARFITM (v/s)		0.145
CRP (mg/dL)		0.495
METAVIR score		0.801
Extent of hepatic resection[26]	2.296 (0.707-0.936)	0.009		0.86

PT-INR: Prothrombin time-international normalized ratio; ICG-R15: Indocyanine green retention rate at 15 min; ARFI: Acoustic radiation force impulse; CRP: C-reactive protein.