Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication

Table 1 Baseline characteristics of patients enrolled in the study

Characteristics	All patients (n = 303)	With HCC development (n = 8)	Without HCC development (n = 295)	P value
Age, yr	57 (20-85)	62 (49-71)	57 (20-85)	0.1982
Males	182 (60.0)	6 (75.0)	176 (59.7)	0.4843
BMI (kg/m2)	23.3 (15.3-39.5)	23.8 (20.2-26.5)	23.4 (15.3-39.5)	0.8602
Habitual drinker	75 (24.8)	2 (25.0)	73 (24.7)	1.0003
Diabetes mellitus1	25 (8.3)	3 (37.5)	22 (7.5)	0.0193
HCV-RNA (logIU/mL)1	6.2 (1.2-7.6)	5.7 (5.0-6.7)	6.2 (1.2-7.6)	0.2462
HCV genotype 1	152 (50.2)	6 (75.0)	146 (49.5)	0.2833
Stage of fibrosis F3-F4	47 (15.5)	6 (75.0)	41 (13.9)	< 0.0013
Grade of inflammation A2-A3	208 (68.6)	8 (100.0)	200 (67.8)	0.0603
Albumin (g/dL)	4.2 (3.3-4.8)	3.9 (3.3-4.4)	4.2 (3.3-4.7)	0.0322
ALT (IU/L)	52 (11-699)	146 (31-209)	52 (11-699)	0.0172
Platelet count (× 104/μL)	17.5 (5.6-39.6)	10.3 (7.9-19.3)	17.6 (5.6-31.9)	0.0062
GGT (IU/L)	37 (9-517)	66 (28-161)	36 (9-517)	0.0532
AFP (ng/mL)1	5 (1-1380)	11 (5-870)	5 (1-1380)	0.0022
PI use	43 (14.2)	1 (12.5)	42 (14.2)	1.0002

¹Data not available for all patients;

²Mann Whitney-U test;

³χ² test. Data are expressed as medians (range) or numbers (%). P values are for comparisons between patients with and without HCC development. AFP: α-fetoprotein; ALT: Alanine aminotransferase; BMI: Body mass index; GGT: γ-glutamyl transpeptidase; HCV: Hepatitis C virus; PI: Protease inhibitor.

Table 2 Univariate and multivariate analyses for factors associated with hepatocellular carcinoma development

Variables	HR (95%CI)	P value
Univariate analysis
Age (by each year)	1.04 (0.31-1.11)	0.347
Male sex	1.61 (0.32-8.04)	0.564
BMI (by each kg/m2)	1.00 (0.80-1.25)	0.982
Habitual drinker	1.26 (0.25-6.27)	0.775
Diabetes mellitus	5.58 (1.19-26.21)	0.030
HCV-RNA (by each logIU/mL)	0.87 (0.44-1.72)	0.696
HCV genotype 1	2.90 (0.58-14.35)	0.195
Stage of fibrosis	3.59 (1.68-7.68)	0.001
Grade of inflammation	4.32 (1.02-18.40)	0.048
Albumin (by each g/dL)	0.03 (0.00-0.29)	0.003
ALT (by each IU/L)	1.00 (1.00-1.01)	0.196
Platelet count (by each 104/mL)	0.75 (0.63-0.90)	0.002
GGT (by each IU/L)	1.00 (1.00-1.01)	0.452
AFP (by each ng/mL)	1.00 (1.00-1.00)	0.033
PI use	2.93 (0.31-27.70)	0.347
AKR1B10 (by each %)	1.06 (1.03-1.10)	< 0.001
Multivariate analysis
AKR1B10 (by each %)	1.04 (1.03-1.10)	0.001

AFP: α-fetoprotein; AKR1B10: Aldo-keto reductase family1 member B10; ALT: Alanine aminotransferase; BMI: Body mass index; GGT: γ-glutamyl transpeptidase; HCV: Hepatitis C virus; PI: Protease inhibitor.

Table 3 Characteristics of the 8 patients with hepatocellular carcinoma development

	Age (yr)	Sex	Interval (yr)	F	A	Albumin (g/dL)	ALT (IU/L)	Platelet count (× 104/mL)	AKR1B10
1	62	F	1.0	2	2	4.0	199	10.3	60%
2	69	F	1.8	3	2	3.3	60	9.9	7%
3	61	M	2.8	2	2	4.4	135	10.3	13%
4	65	M	3.8	4	3	3.4	88	9.0	52%
5	49	M	4.3	3	2	3.8	209	7.9	38%
6	56	M	4.9	3	2	4.2	156	19.3	9%
7	57	M	5.8	3	2	4.2	157	14.7	16%
8	71	M	9.0	3	2	3.7	31	17.9	0%

AKR1B10: Aldo-keto reductase family1 member B10; ALT: Alanine aminotransferase; HCC: Hepatocellular carcinoma.