Clinical course of sub-centimeter-sized nodules detected during surveillance for hepatocellular carcinoma

Table 1 Baseline characteristics of high-risk patients who had sub-centimeter-sized nodules (n = 142)

Baseline characteristics	Number of patients
Age (yr)	50.2 ± 9.4
Male	84 (59.2)
Etiology of liver disease
Hepatitis B infection	126 (88.7)
Hepatitis C infection	9 (6.3)
Alcohol liver cirrhosis	7 (5.0)
Liver cirrhosis	111 (78.2)
Child-Pugh A	98 (88.3)
Child-Pugh B	10 (9.0)
Child-Pugh C	3 (2.7)
AST (UI/L)	47.9 ± 26.8
ALT (UI/L)	53.2 ± 42.5
PT (INR)	1.19 ± 0.17
Bilirubin (mg/dL)	1.24 ± 0.97
Platelets (109/L)	125.3 ± 60.3
Albumin (g/dL)	3.77 ± 0.56
Baseline AFP (ng/mL, range)	5.7 (1.0-211.6)
Number of nodules
One	26 (18.3)
Two	7 (5.0)
Three	3 (2.1)
Four	1 (0.7)
Over four	105 (73.9)
Nodule pattern
Hypoechoic/low-attenuation	77 (54.3)
Hyperechoic/high-attenuation	31 (21.8)
Mixed	34 (23.9)
Initial radiologic diagnosis
RN/DN	119 (83.8)
Hemangioma	17 (12.0)
Indeterminate nodule	5 (3.5)
Arterioportal shunt	1 (0.7)

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PT: Prothrombin time; AFP: Alpha-fetoprotein; RN: Regenerative nodule; DN: Dysplastic nodule; INR: International normalized ratio. Data are shown as the mean ± SD, median (range) or n (%) of patients.

Table 2 Risk factors for the development of hepatocellular carcinoma from sub-centimeter-sized nodules

Variables	Diagnosis		P value
	HCC (n = 33)	Non-HCC (n = 109)
Age (yr)	54.4 ± 8.3	48.9 ± 9.4	0.003
Male	24 (72.4)	60 (55.0)	0.070
Etiology of liver disease			0.364
Hepatitis B infection	27 (81.8)	99 (90.8)
Hepatitis C infection	3 (9.1)	6 (5.5)
Alcoholic liver cirrhosis	3 (9.1)	4 (3.7)
Liver cirrhosis	29 (87.9)	82 (75.2)	0.123
AST (UI/L)	49.3 ± 20.4	47.5 ± 28.5	0.736
ALT (UI/L)	50.9 ± 36.5	53.9 ± 44.3	0.722
PT (INR)	1.23 ± 0.17	1.18 ± 0.17	0.088
Bilirubin (mg/dL)	1.27 ± 0.78	1.23 ± 1.02	0.831
Platelets (109/L)	110.1 ± 53.9	129.9 ± 61.6	0.099
Albumin (g/dL)	3.56 ± 0.58	3.84 ± 0.55	0.012
Number of nodules			0.390
One	4 (12.1)	22 (20.0)
Two	1 (3.0)	6 (5.5)
Three	0 (0.0)	3 (2.8)
Four	0 (0.0)	1 (0.9)
Over four	28 (84.8)	77 (70.6)
Nodule pattern			0.011
Hypoechoic/low-attenuation	23 (69.7)	54 (49.5)
Hyperechoic/high-attenuation	1 (3.0)	30 (27.5)
Mixed	9 (27.3)	25 (22.9)
Initial radiologic diagnosis			0.036
RN/DN	31 (93.9)	88 (80.7)
Hemangioma	0 (0.0)	17 (15.6)
Indeterminate nodule	2 (6.1)	3 (2.8)
Arterioportal shunt	0 (0.0)	1 (0.9)
Baseline AFP (ng/mL, range)	8.5 (3.2-211.6)	5.4 (1.0-55.9)	0.035

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PT: Prothrombin time; AFP: Alpha-fetoprotein; RN: Regenerative nodule; DN: Dysplastic nodule; INR: International normalized ratio; HCC: Hepatocellular carcinoma. Data are shown as the mean ± SD, median (range) or n (%) of patients.

Table 3 Multivariate analysis of risk factors for the development of hepatocellular carcinoma from sub-centimeter-sized hepatic nodules

Variables	P value	OR	95% CI
Age (yr)	0.012	1.075	1.016-1.137
Male	0.009	3.969	1.403-11.226
PT (INR)	0.877	0.698	0.007-66.718
Platelets (109/L)	0.917	0.999	0.990-1.009
Albumin (g/dL)	0.478	0.624	0.169-2.298
Nodule pattern	0.081
Nodule pattern (1)1	1.000	0.812	0.233-2.827
Nodule pattern (2)2	0.054	0.075	0.006-1.026
Baseline AFP (ng/mL)	0.024	1.039	1.005-1.073

¹Between hypoechoic/low-attenuation and mixed echoic/attenuation;

²Between hyperechoic/high-attenuation and mixed echoic/attenuation. OR: Odds ratio; CI: Confidence interval; PT: Prothrombin time; AFP: Alpha-fetoprotein; INR: International normalized ratio. Data are shown as the mean ± SD, median (range) or number (%) of patients.