ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma

doi:10.4251/wjgo.v11.i5.424

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. May 15, 2019; 11(5): 424-435
Published online May 15, 2019. doi: 10.4251/wjgo.v11.i5.424

Table 1 Characteristics of patients with hepatocelullar carcinoma receiving sorafenib treatment according to treatment outcomes

Variable	Total(n = 41)	SD + PR + CR(n = 17)	PD(n = 24)	P value
Age (yr)	74.0 (69.0-81.0)	74.0 (71.0-78.0)	74.0 (63.5-70.0)	0.400
Sex (male/female)	38/3	17/0	21/3	0.254
Etiology (HBV/HCV/NASH/alcohol)	7/20/3/11	0/13/1/3	7/7/2/8	0.0707
Albumin (g/dL)	3.6 (3.3-3.9)	3.7 (3.5-4.0)	3.5 (3.3-3.7)	0.0827
Prothrombin time (%)	82.0 (77.0-89.0)	83.0 (78.0-89.0)	82.0 (78.5-91.0)	0.751
Total bilirubin (mg/dL)	0.8 (0.6-0.9)	0.7 (0.5-0.9)	0.8 (0.6-0.9)	0.397
Platelet count (× 10⁴/mm³)	14.1 (11.1-17.3)	16.1 (9.4-18.3)	14.1 (11.6-16.9)	0.568
AFP (ng/mL)	121.8 (11.3-2611.0)	31.8 (6.7-161.0)	286.0 (41.6-5193.5)	0.103
DCP (mAU/mL)	359.5 (58.0-5277.5)	192 (24.5-5177)	5177 (183-17214)	0.012
AFP-L3% (%)	13.2 (1.7-42.4)	12.3 (1.45-34.3)	21.8 (1.85-47.7)	0.529
VEGF (pg/mL)	25.8 (14.1-40.1)	18.5 (10.0-35.1)	28.2 (22.0-50.7)	0.106
VEGFR-2 (pg/mL)	6500 (5750-7400)	6400 (5200-7100)	6800 (6350-7600)	0.211
Maximum tumor size (cm)	3.3 (2.5-7.7)	3.2 (2.0-6.0)	4.3 (2.7-10.8)	0.220
Tumor number (1/2/3/4 or more/only distant metastasis)	3/2/1/33/2	0/2/1/13/1	3/0/0/20/1	0.131
PVTT (presence/absence)	7/34	2/15	5/19	0.679
Distant metastasis (presence/absence)	17/24	10/7	7/17	0.107
Child-pugh score	5 (5-6)	5 (5-6)	5 (5-6)	0.469
UICC TNM stage (2/3/4)	5/16/20	1/6/10	4/10/10	0.455
Observation (survival) period (d)	328 (156-530)	564 (405-880)	162 (116-319)	0.000322

Data are expressed as median (Interquartile range). P-values represent comparisons between patients with HCC who had SD+PR+CR and PD. HCC: Hepatocelullar carcinoma; HCV: Hepatitis C virus; HBV: Hepatitis B virus; NASH: Non-alcoholic steatohepatitis; AFP: Alpha fetoprotein; DCP: Des-γ-carboxy prothrombin; AFP-L3%: Lens culinaris agglutinin-reactive alpha-fetoprotein; VEGF: Vascular endothelial growth factor; VEGFR-2: VEGF receptor-2; PVTT: Portal vein tumor thrombosis; UICC: The Union for the International Cancer Control; TNM stage: Tumor-node-metastasis stage; SD: Stable disease; PR: Partial response; CR: Complete response; PD: Progressive disease.

Table 2 Predictive factors for sorafenib response

Univariate analysis	OR (95%CI)	P value
Age (per 1 yr increase)	1.05 (0.967-1.13)	0.2660
Sex (male vs female)	0.556 (0.0464-6.66)	0.9950
Viral hepatitis (presence vs absence)	0.527(0.123-2.27)	0.6430
Albumin (per 1 g/dL decrease)	6.59 (0.827-52.6)	0.0750
Prothrombin time (per 1% decrease)	0.977 (0.928-1.03)	0.3910
Total bilirubin (per 1 mg/dL increase)	0.376 (0.0378-3.74)	0.4040
Platelet count (per 10⁴/µL decrease)	1.040 (0.937-1.14)	0.4970
AFP (per 1 ng/mL increase)	1.000 (1.000-1.00)	0.5330
DCP (per 1 mAU/mL increase)	1.00 (0.999-1.00)	0.1100
AFP-L3% (per 1% increase)	1.00 (0.996-1.01)	0.4420
VEGF (per 1 pg/mL increase)	0.98 (0.949-1.01)	0.1950
VEGFR-2 (per 1 pg/mL increase)	1.00 (0.999-1.000)	0.2210
Maximum tumor size (per 1 cm increase)	0.892 (0.752-1.06)	0.1900
Tumor number (per 1 increase)	1.11 (0.646-1.90)	0.7070
PVTT (presence vs absence)	0.835 (0.455-1.53)	0.5590
Distant metastasis (presence vs absence)	2.450 (0.64-9.37)	0.1910
ADAMTS13:AC (per 1% increase)	1.020 (1.0001-1.050)	0.0039
VWF:Ag (per 1% increase)	0.996 (0.991-1.000)	0.0740
VWF:Ag/ADAMTS13:AC (per 1 increase)	0.465 (0.265-0.817)	0.0077
Multivariate analysis
VWF:Ag/ADAMTS13:AC (per 1 increase)	0.495 (0.281-0.870)	0.0147

AFP: Alpha fetoprotein; DCP: Des-γ-carboxy prothrombin; AFP-L3%: Lens culinaris agglutinin-reactive alpha-fetoprotein; VEGF: Vascular endothelial growth factor; VEGFR-2: VEGF receptor-2; PVTT: Portal vein tumor thrombosis; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13; ADAMTS13:AC: ADAMTS13 activity; VWF: Von Willebrand factor; VWF: Ag: VWF antigen; VWF:Ag/ADAMTS13:AC ratio: The ratio of VWF:Ag to ADAMTS13:AC; OR: Odds ratio; CI: Confidence interval.

Table 3 Prognostic factors for patients with hepatocellular carcinoma receiving sorafenib treatment

Univariate analysis	HR (95%CI)	P value
Age (per 1 yr increase)	1.16 (1.032-1.304)	0.0127
Sex (male vs female)	0.062 (0.000382-1.008)	0.0561
Viral hepatitis (presence vs absence)	1.416(0.405-4.95)	0.5862
Albumin (per 1 g/dL decrease)	0.427 (0.0750-2.44)	0.3388
Prothrombin time (per 1% decrease)	1.008 (0.969-1.048)	0.3910
Total bilirubin (per 1 mg/dL increase)	4.203 (0.417-42.30)	0.2230
Platelet count (per 10⁴/µL decrease)	0.906 (0.807-1.018)	0.4970
AFP (per 1 ng/mL increase)	1.000 (1.000-1.00)	0.3334
DCP (per 1 mAU/mL increase)	1.000 (1.000-1.00)	0.0136
AFP-L3% (per 1% increase)	0.999 (0.969-1.031)	0.9484
VEGF (per 1 pg/mL increase)	0.982 (0.952-1.01)	0.2426
VEGFR-2 (per 1 pg/mL increase)	1.00 (0.999-1.000)	0.8947
Maximum tumor size (per 1 cm increase)	1.026 (0.868-1.214)	0.7622
Tumor number (per 1 increase)	0.751 (0.5-1.129)	0.1690
PVTT (presence vs absence)	0.347 (0.0384-3.141)	0.3464
Distant metastasis (presence vs absence)	0.489 (0.129-1.854)	0.2936
ADAMTS13:AC (per 1% increase)	0.936 (0.895-0.978)	0.0035
VWF:Ag (per 1% increase)	0.996 (0.991-1.000)	0.9227
VWF:Ag/ADAMTS13:AC (per 1 increase)	1.33 (0.998-1.772)	0.0520
Multivariate analysis
ADAMTS13:AC (per 1% increase)	0.937 (0.895-0.980)	0.0045

HCC: Hepatocellular carcinoma; AFP: Alpha fetoprotein; DCP: Des-γ-carboxy prothrombin; AFP-L3%: Lens culinaris agglutinin-reactive alpha-fetoprotein; VEGF: Vascular endothelial growth factor; VEGFR-2: VEGF receptor-2; PVTT: Portal vein tumor thrombosis; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13; ADAMTS13:AC: ADAMTS13 activity; VWF: Von Willebrand factor; VWF:Ag: VWF antigen; VWF:Ag/ADAMTS13:AC ratio: The ratio of VWF:Ag to ADAMTS13:AC; HR: Hazard ratio; CI: Confidence interval.

Citation: Takaya H, Namisaki T, Shimozato N, Kaji K, Kitade M, Moriya K, Sato S, Kawaratani H, Akahane T, Matsumoto M, Yoshiji H. ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma. World J Gastrointest Oncol 2019; 11(5): 424-435
URL: https://www.wjgnet.com/1948-5204/full/v11/i5/424.htm
DOI: https://dx.doi.org/10.4251/wjgo.v11.i5.424