Novel Preoperative Type IV Collagen to Predict the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Cirrhotic Portal Hypertension After Laparoscopic Splenectomy and Azygoportal Disconnection

Figures & data

Figure 1 CONSORT diagram.

Notes: CONSORT figure adapted from Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials. PLoS Med. 2010;7(3): e1000251.²¹ Copyright: © 2010 Schulz et al. Creative Commons Attribution License.

Table 1 Demographic and Preoperative Clinical Characteristics Between Non-HCC and HCC Groups in Unadjusted and IPTW Adjusted Population

Characteristics	Unadjusted			IPTW Adjusted
	Non-HCC	HCC	P	Non-HCC	HCC	P
	N = 169	N = 9		N = 177.6	N = 160
Age (years)	52.02 ± 10.33	53.89 ± 8.84	0.595	52.12 ± 10.40	56.77 ± 7.20	0.183
Gender			0.726			0.669
Male	112 (66.3)	7 (77.8)		118.7 (66.8)	89.3 (55.8)
Female	57 (33.7)	2 (22.2)		58.9 (33.2)	70.8 (44.2)
Year of treatment			0.371			0.603
2012–2016	77 (45.6)	6 (66.7)		82.7 (46.6)	55.9 (34.9)
2017–2022	92 (54.4)	3 (33.3)		94.8 (53.4)	104.1 (65.1)
Hypertension			0.369			0.185
No	142 (84.0)	6 (66.7)		147.6 (83.1)	87.4 (54.6)
Yes	27 (16.0)	3 (33.3)		30.0 (16.9)	72.6 (45.4)
Diabetes			0.070			0.506
No	143 (84.6)	5 (55.6)		147.8 (83.2)	114.2 (71.4)
Yes	26 (15.4)	4 (44.4)		29.7 (16.8)	45.8 (28.6)
Portal vein thrombosis			0.596			0.830
No	151 (89.3)	7 (77.8)		157.9 (88.9)	145.6 (91.0)
Yes	18 (10.7)	2 (22.2)		19.6 (11.1)	14.4 (9.0)
Child-Pugh Classification			0.600			0.789
A	107 (63.3)	7 (77.8)		113.4 (63.9)	111.9 (70.0)
B	62 (36.7)	2 (22.2)		64.2 (36.1)	48.1 (30.0)
BMI	23.82 ± 3.27	23.70 ± 4.44	0.914	23.83 ± 3.27	23.71 ± 2.31	0.846
Splenic vein diameter (mm)	11.94 ± 3.11	10.39 ± 3.22	0.146	11.89 ± 3.11	11.72 ± 1.76	0.748
Longitudinal diameter of spleen (mm)	178.75 ± 28.04	168.11 ± 45.72	0.287	178.25 ± 28.25	164.07 ± 32.33	0.227
Portal vein diameter (mm)	13.82 ± 2.29	13.51 ± 2.14	0.689	13.82 ± 2.29	13.47 ± 2.20	0.755
WBC (× 10^9/L)	2.29 ± 0.76	2.21 ± 0.73	0.772	2.28 ± 0.76	2.00 ± 0.68	0.373
HGB (g/L)	106.92 ± 18.56	109.44 ± 17.58	0.690	107.01 ± 18.53	104.61 ± 12.31	0.590
PLT (× 10^9/L)	51.34 ± 14.71	56.11 ± 18.68	0.351	51.52 ± 14.77	52.76 ± 13.32	0.840
ALT (U/L)	25.41 ± 15.19	22.22 ± 8.89	0.534	25.28 ± 15.08	21.74 ± 6.15	0.101
INR	1.32 ± 0.17	1.31 ± 0.14	0.780	1.32 ± 0.17	1.28 ± 0.09	0.113
BUN (mmol/L)	5.81 ± 2.42	6.52 ± 3.27	0.401	5.86 ± 2.46	5.18 ± 3.08	0.650
Cr (umol/L)	80.44 ± 19.52	80.56 ± 16.35	0.986	80.43 ± 19.53	76.97 ± 15.29	0.620
LN (µg/L)	31.44 (15.93–53.16)	46.78 (23.55–49.95)	0.467	31.42 (15.87–53.20)	35.48 (23.11–46.88)	0.245
C-IV (µg/L)	37.01 (24.45–54.45)	95.53 (87.63–115.38)	<0.001	36.80 (24.30–54.48)	77.61 (66.27–91.05)	<0.001
HA (µg/L)	78.20 (50.00–128.66)	104.50 (82.99–246.79)	0.094	78.13 (50.20–128.86)	82.92 (81.62–251.28)	0.600
PC-III (µg/L)	37.69 (24.48–54.52)	46.26 (36.94–50.22)	0.266	37.50 (24.45–54.43)	38.28 (36.78–41.88)	0.417
AFP (ng/mL)	2.30 (1.34–3.95)	4.44 (3.09–10.04)	0.015	2.30 (1.34–3.91)	3.32 (2.59–7.17)	0.044
FIB-4	5.97 (4.15–8.54)	7.70 (7.22–7.79)	0.050	5.96 (4.13–8.48)	7.23 (7.17–8.91)	0.021

Notes: Data shown as mean ± standard deviation, number (percentages), or median (interquartile range), as indicated.

Abbreviations: HCC, hepatocellular carcinoma; IPTW, inverse treatment probability weighting; BMI, body mass index; WBC, white blood cells; HGB, hemoglobin; PLT, platelets; ALT, alanine aminotransferase; INR, international normalized ratio; BUN, blood urea nitrogen; Cr, creatinine; LN, laminin; C-IV, type IV collagen; HA, hyaluronidase; PC-III, procollagen type III; AFP, alpha fetoprotein; FIB-4, fibrosis-4 score.

Table 2 Correlation Analysis of HCC with C-IV, AFP, FIB-4, and IVAFP-FIB-4

Characteristics	Correlation Coefficient	P
C-IV (µg/L) (cutoff value: 73.95)	0.585	<0.001
AFP (ng/mL) (cutoff value: 2.08)	0.192	0.010
FIB-4 (cutoff value: 6.92)	0.277	<0.001
IVAF-FIB-4*	0.835	<0.001

Notes: *IVAF-FIB-4: When C-IV level ≥73.95 µg/L, AFP level ≥2.08 ng/mL, and FIB-4 ≥6.917 were met at the same time, the indicator was assigned a value of 1, and the other cases were assigned a value of 0.

Abbreviations: C-IV, type IV collagen; AFP, alpha fetoprotein; FIB-4, fibrosis-4 score; IVAFP-FIB-4, type IV collagen-alpha fetoprotein-fibrosis-4 score.

Figure 2 Receiver operating characteristic curve analysis to assess the accuracy of candidate variables and the non-invasive predictive indicator in discriminating patients with and without HCC.

Figure 3 The proportion of occurrence of HCC in HBV-related CPH patients with different groups. (*IVAF-FIB-4: When C-IV level ≥73.95 µg/L, AFP level ≥2.08 ng/mL, and FIB-4 ≥6.917 were met at the same time, the indicator was assigned a value of 1, and the other cases were assigned a value of 0.

Figure 4 The incidence density of HCC in HBV-related CPH patients with different groups. (*IVAF-FIB-4: When C-IV level ≥73.95 µg/L, AFP level ≥2.08 ng/mL, and FIB-4 ≥6.917 were met at the same time, the indicator was assigned a value of 1, and the other cases were assigned a value of 0.

Table 3 Logistic Regression Analysis of Occurrence of HCC in Unadjusted and IPTW Adjusted Population

Characteristics	Unadjusted		IPTW Adjusted
	OR [95% CI]	P	OR [95% CI]	P
IVAF-FIB-4* (1/0)	668.000 (53.895–8279.541)	<0.001	3244.565 (316.198–33,293.081)	<0.001

Notes: *IVAF-FIB-4: When C-IV level ≥73.95 µg/L, AFP level ≥2.08 ng/mL, and FIB-4 ≥6.917 were met at the same time, the indicator was assigned a value of 1, and the other cases were assigned a value of 0.

Abbreviations: HCC, hepatocellular carcinoma; IPTW, inverse probability of treatment weighting; OR, odds ratio; CI, confidence interval; C-IV, type IV collagen; AFP, alpha fetoprotein; FIB-4, fibrosis-4 score; IVAFP-FIB-4, type IV collagen-alpha fetoprotein-fibrosis-4 score.

Schulz KF, Altman DG, Moher D. CONSORT statement: updated guidelines for reporting parallel group randomised trials. PLoS Med. 2010;7(3):e1000251.

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