Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients

Table 1 Baseline characteristics of non-steatohepatitis patients without and with hepatocellular carcinoma

Variable	Total (n = 33)	Patients without HCC (n = 19)	Patients with HCC (n = 14)	P value
Age (yr)	73 (66–77)	73 (68–77)	72 (66–78)	NS
Sex (male ⁄ female)	20 ⁄ 13	9 ⁄ 10	11 ⁄ 3	NS
HBV/HCV/AIH	20/9/4	11/5/3	9/4/1	NS
Albumin (g/dL)	4.2 (3.8-4.5)	4.4 (4.3-4.6)	4.0 (3.8-4.1)	< 0.05
Total bilirubin (mg/dL)	0.8 (0.7-1.2)	0.8 (0.8-1.2)	0.9 (0.6-1.2)	NS
Aspartate aminotransferase (IU/L)	29 (25-38)	29 (26-34)	28 (24-4)	NS
Alanine aminotransferase (IU/L)	24 (17-36)	21 (17-34)	27 (19-38)	NS
Alkaline phosphatase (IU/L)	314 (233-442)	314 (232-451)	343 (2252-432)	NS
γ-glutamyl transpeptidase (IU/L)	34 (24-45)	34 (24-43)	38 (24-63)	NS
Prothrombin time (%)	83 (75-90)	81 (77-86)	88 (68-96)	NS
Child–Pugh score	5.0 (5-6)	5.0 (5-5)	5.0 (5-6)	NS
Platelet count (× 104⁄μL)	12.9 (9.2-15.1)	11.9 (9.1-14.5)	13.6 (9.9-16.2)	NS
Maximum tumor size (cm)			1.2 (1.1-1.3)
Total tumor volume (cm3)			6.3 (5.0-14.2)
UICC TNM stage (stage 1/stage 2/stage 3)			1/9/4

Data are expressed as the median (interquartile range). P-values represent comparisons between non-steatohepatitis patients with and without hepatocellular carcinoma. HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; HCV: Hepatitis C virus; AIH: Autoimmune hepatitis; UICC: Union for International Cancer Control; TNM: Tumor-node-metastasis.

Table 2 Diagnostic accuracy of biomarkers for the early diagnosis of hepatocellular carcinoma

Variable	OR (95%CI)	P value
Univariate analysis
AFP > 10 ng/mL	1.67 (0.332-8.37)	0.535
DCP > 40 mAU/mL	8.00 (0.776-82.5)	0.0806
AFP-L3% > 5%	1.35 (0.999-1.84)	0.0221
VEGF > 60pg/mL	2.67 (0.630-1.3)	0.183
VEGFR-2 > 6500 pg/mL	2.83 (0.666-12.0)	0.159
Total carnitine (per 1 μmol/L increase)	0.979 (0.933-1.03)	0.380
Free carnitine (per 1 μmol/L increase)	0.991 (0.943-1.04)	0.710
Acylcarnitine (per 1 μmol/L increase)	0.0865 (0.0158-0.475)	0.0049
Multivariate analysis
Acylcarnitine (per 1 μmol/L increase)	0.0941 (0.00137-0.646)	0.0162

HCC: Hepatocellular carcinoma; AFP: α-Fetoprotein; DCP: Des-γ-carboxy prothrombin; AFP-L3%: Lens culinaris agglutinin-reactive α-fetoprotein; VEGF: Vascular endothelial growth factor; VEGFR-2: VEGF receptor-2; CI: Confidence interval; OR: Odds ratio.

Table 3 Profiles of acylcarnitine in non-steatohepatitis patients without and with hepatocellular carcinoma

Variable	Patients without HCC (n = 19)	Patients with HCC (n = 14)	P value
Acetylcarnitine (AC2)	3.96 (3.33–4.92)	2.06 (1.335–2.255)	< 0.05
Propionylcarnitine (AC3)	0.339 (0.2875–0.4115)	0.3375 (< 0.24–0.473)	NS
Butyrylcarnitine (AC4)	< 0.1 (< 0.1–0.1)	0.0795 (< 0.1–0.196)	NS
Isovalerylcarnitine (AC5)	< 0.06 (< 0.06–0.1085)	< 0.06 (< 0.06–0.0787)	NS
Glutarylcarnitine (AC5DC)	< 0.05 (< 0.05–0.05)	< 0.05 (< 0.05–0.05)	NS
3-hydroxy isovalerylcarnitine (AC5OH)	< 0.1 (< 0.1–0.1)	< 0.1 (< 0.1–0.1)	NS
Hexanoylcarnitine (AC6)	0.0531 (< 0.05–0.0596)	< 0.05 (< 0.05–0.05)	< 0.05
Octanoylcarnitine (AC8)	0.176 (0.1425–0.2375)	0.0871 (0.0622–0.11025)	< 0.05
Decanoylcarnitine (AC10)	0.335 (0.256–0.432)	0.1315 (0.099675–0.171)	< 0.05
Dodecanolycarnitine (AC12)	0.105 (0.0849–0.1335)	0.02725 (0–0.06195)	< 0.05
Myristoylcarnitine (AC14)	< 0.06 (< 0.06–0.06)	< 0.06 (< 0.06–0.06)	NS
Myristoleylcarnitine (AC14:1)	0.185 (0.134–0.2325)	0.07825 (0.06305–0.09855)	< 0.05
Palmitoylcarnitine (AC16)	0.133 (0.1255–0.1485)	0.116 (0.10425–0.1310)	NS
3-hydroxy palmitoylcarnitine (AC16OH)	< 0.03 (< 0.03–0.03)	< 0.03 (< 0.0 –0.03)	NS
Octadecanoylcarnitine (AC18)	0.0429 (0.03245–0.04775)	0.03315 (0.006625–0.039525	< 0.05
Oleoylcarnitine (AC18:1)	0.871 (0.6825–1.0350)	0.721 (0.61275–0.83775)	NS
3-hydroxy octadecenoylcarnitine (AC18:1OH)	< 0.025 (< 0.025–0.02615)	< 0.025 (< 0.025–0.025)	NS
Short-chain fatty acids (AC2–AC6)	4.3362 (3.83995–5.561750)	2.4316 (1.86085–2.994125)	< 0.05
Medium-chain fatty acids (AC8 + AC10)	0.50600 (0.40700–0.69100)	0.21385 (0.16545–0.28075)	< 0.05
Long-chain fatty acid (AC12–AC18:1OH)	1.3668 (1.106550–1.5871)	0.9425 (0.836625–1.1087)	< 0.05

Data are expressed as the median (interquartile range). P-values represent comparisons between non-steatohepatitis patients with and without hepatocellular carcinoma. HCC: Hepatocellular carcinoma.