Assessment of fibroblast growth factor 19 as a non-invasive serum marker for hepatocellular carcinoma

Table 1 Characteristics of all participants

		Control (n = 30)	Cirrhosis (n = 30)	HCC (n = 30)	P value	Post-hoc analysis
Age (yr)		51.07 ± 12.38	53.57 ± 10.48	57.37 ± 10.25	0.091
Sex	Female	12 (40%)	10 (33.3%)	11 (36.7%)	0.866
	Male	18 (60%)	20 (66.7%)	19 (63.3%)
Aetiology of hepatic disease			HCV (n = 18, 60%)	HCV (n = 25, 83.33%)	0.691
			HBV (n = 7, 23.3%)	HBV (n = 3, 10%)
			Others (n = 5, 16.6%)	Others (n = 2, 6.66%)
Child-Pugh Class	Class A		18 (60%)	5 (16.7%)	0.002
	Class B		6 (20%)	11 (36.7%)
	Class C		6 (20%)	14 (46.7%)
Fibroblast growth factor 19 (pg/mL)		69.60 ± 20.90	125.63 ± 31.54	236.44 ± 40.94	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 ≤ 0.001
Alpha fetoprotein (ng/mL)		3.35 (2.5 – 4.5)	6.4 (4 – 6.9)	513.5 (5.6 – 1500)	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 ≤ 0.001
Haemoglobin (g/dL)		13.16 ± 1.24	10.68 ± 1.11	10.49 ± 1.59	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 = 0.588
White blood cells (109/L)		7.09 ± 2.01	6.37 ± 2.27	5.86 ± 2.43	0.109
Platelets (109/L)		288.10 ± 92.79	144.17 ± 48.27	136.13 ± 43.78	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 = 0.636
Alanine aminotransferase (U/L)		20.67 ± 7.02	65.47 ± 33.00	52.97 ± 23.25	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 = 0.044
Aspartate aminotransferase (U/L)		23.23 ± 12.69	49.87 ± 24.78	45.93 ± 20.02	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 = 0.444
Creatinine (mg/dL)		0.90 ± 0.22	0.99 ± 0.36	1.11 ± 0.51	0.112
Urea (mg/dL)		21.70 ± 7.37	30.10 ± 18.82	32.97 ± 25.17	0.057
Albumin (g/dL)		3.96 ± 0.34	3.33 ± 0.53	2.65 ± 0.43	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 ≤ 0.001
INR		1.09 ± 0.11	1.54 ± 0.24	1.85 ± 0.36	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 ≤ 0.001
Bilirubin (mg/dL)		0.75 ± 0.26	1.80 ± 0.74	1.97 ± 0.42	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 = 0.211
Fasting blood glucose (µmoI/L)		5.19 ± 0.19	4.46 ± 0.28	4.46 ± 0.28	≤ 0.001	P1 ≤ 0.001
						P2 ≤ 0.001
						P3 = 1.000

HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; INR: International normalised ratio.

Table 2 Serum fibroblast growth factor 19 levels in the cirrhosis and hepatocellular carcinoma groups according to Child-Pugh score

	Child-Pugh Class	Cirrhosis (n = 30)	HCC (n = 30)
Fibroblast growth factor 19 (pg/mL)	Class A	129.311 (± 38.01)	223.320 (± 37.39)
	Class B	123.383 (± 21.51)	230.209 (± 30.96)
	Class C	116.833 (± 15.69)	246.029 (± 48.71)
	P value	0.7046	0.479

HCC: Hepatocellular carcinoma.

Table 3 Tumour characteristics of hepatocellular carcinoma cases

		HCC (n = 30)
Size	< 2 cm	3 (10%)
	2-3 cm	17 (56.7%)
	> 5 cm	10 (33.3%)
Number of tumour foci	Single	10 (33.3%)
	2-3	9 (30%)
	Multiple	11 (36.7%)
Portal vein thrombosis	No	21 (70%)
	Yes	9 (30%)
Metastasis	No	27
	Yes	3

HCC: Hepatocellular carcinoma.

Table 4 Serum fibroblast growth factor 19 levels according to variables in the hepatocellular carcinoma group

		FGF-19 pg/mL (mean ± SD)	P value
Size	< 2 cm	219.9 ± 51.79	0.254
	2-3 cm	229.2 ± 36.06
	> 5 cm	253.72 ± 44.39
Number	Single	234.17 ± 36.38	0.885
	2 - 3	242.28 ± 45.69
	Multiple	233.74 ± 44.22
Portal vein thrombosis	No	230.55 ± 39.13	0.235
	Yes	250.2 ± 44.08
Right upper quadrant pain	No	237.171 ± 41.026	0.885
	Yes	234.744 ± 43.163
Weight loss	No	229.132 ± 34.285	0.106
	Yes	256.550 ± 52.793
Pruritus	No	239.518 ± 39.170	0.505
	Yes	227.988 ± 47.214
Jaundice	No	226.182 ± 29.468	0.118
	Yes	249.86 ± 50.48
Fever	No	237.668 ± 40.531	0.834
	Yes	234.33 ± 43.54
Oedema	No	228.945 ± 37.054	0.16
	Yes	251.44 ± 46.12

FGF-19: Fibroblast growth factor 19.

Table 5 Correlation between fibroblast growth factor 19 and alpha fetoprotein with patients’ laboratory data

	AFP		FGF-19
	r	P value	r	P value
AFP	–	–	0.383	0.003
FGF-19	0.383	0.003	–	–
Age	0.062	0.640	0.125	0.343
Haemoglobin	-0.196	0.133	-0.060	0.651
White blood cells	-0.064	0.627	-0.144	0.272
Platelets	0.018	0.893	-0.151	0.248
Alanine aminotransferase	0.036	0.786	-0.151	0.249
Aspartate aminotransferase	0.040	0.764	-0.024	0.855
Creatinine	-0.164	0.211	0.093	0.480
Urea	-0.022	0.867	0.012	0.929
Albumin	-0.213	0.102	-0.500	0.000
INR	-0.001	0.993	0.357	0.005
Bilirubin	-0.093	0.479	0.008	0.952
Fasting blood glucose	-0.135	0.477	0.056	0.767

AFP: Alpha fetoprotein; FGF-19: Fibroblast growth factor 19; INR: International normalised ratio.

Table 6 Diagnostic performance of fibroblast growth factor 19 and alpha fetoprotein for differentiation of hepatocellular carcinoma cases

	Cut-off point	AUC	Sensitivity	Specificity	PPV	NPV
FGF-19	> 180 pg/mL	0.98	100%	90%	90%	100%
AFP	> 8.2 ng/mL	0.78	63.33%	83.33%	79.2%	69.4%

AFP: Alpha fetoprotein; AUC: Area under the curve; FGF-19: Fibroblast growth factor 19; HCC: Hepatocellular carcinoma; NPV: Negative predictive value; PPV: Positive predictive value.