Serotonin: is it a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients?

Available online 19 April 2013

Peer review under responsibility of Alexandria University Faculty of Medicine.

Figures & data

Fig. 1 ROC curve for AFP and serotonin in liver Cirrhosis group.

Fig. 2 ROC curve for AFP and serotonin in liver Cirrhosis and HCC group.

Table 1 Clinical data of patients groups

	Group I (n=45)	Group II (n=30)	Test of sig.
Sex
Male	33(73.3%)	17(56.7%)	P=0.134
Female	12(26.7%)	13(43.3%)
Age(years)
Min-Max	38.0-75.0	34.0-74.0	P=0.466
Mean±SD	53.98± 9.07	55.60± 93.95
Median	52.0	54.0
BMI(Kg/m^2)
Min-Max	16.40-37.70	17.10-41.60	P=0.200
Mean±SD	26.56±3.75	27.90±5.17
Median	26.50	27.65
MBP(mmHg)
Min-Max	70.0-120.0	70.0-120.0	P=0.663
Mean±SD	87.57±10.87	89.70±12.79
Median	83.30	83.30
Child class
A	8 (17.8%)	1 (3.3%)	P=0.011*
B	27 (60.0%)	13 (43.3%)
C	10 (22.2%)	16 (53.3%)
Child class score
Min-Max	5.0-13.0	6.0-14.0	P=0.015*
Mean±SD	8.58±1.90	9.63±1.83
Median	9.0	10.0
MELD score
Min-Max	7.0-27.0	7.0-25.0	P=0.235
Mean±SD	13.60±4.91	14.47±4.19
Median	13.0	14.50

Group I= Patients with liver cirrhosis

Group II= Patients with liver cirrhosis and hepatocellular carcinoma

BMI= Body mass index

MBP= Mean blood pressure

MELD= Model of end stage liver disease

Table 2 Laboratory investigations in both patients groups.

	Group I (n=45)	Group II (n=30)	Test of sig.
Creatinine (mg/dl)
Min.-max	0.50 – 2.80	0.60 – 2.20	p = 0.229
Mean ± SD	1.04 ± 0.42	1.10 ± 0.36
Median	0.90	1.10
AST
Min.-max.	10.0 – 186.0	23.0 – 309.0	p = 0.001^*
Mean ± SD	53.40 ± 42.56	88.93 ± 64.90
Median	34.0	78.50
ALT
Min.-max.	7.0 – 97.0	6.0 – 140.0	p = 0.001^*
Mean ± SD	27.36 ± 20.21	44.37 ± 30.88
Median	20.0	33.50
Total Bilirubin
Min.-max.	0.40 – 14.0	0.50 – 25.0	p = 0.058
Mean ± SD	2.56 ± 3.04	4.22 ± 5.16
Median	1.60	2.0
Direct Bilirubin
Min.-max.	0.10 – 10.50	0.30 – 16.30	p = 0.026^*
Mean ± SD	1.40 ± 2.15	2.63 ± 3.54
Median	0.70	1.05
Total Proteins
Min.-max.	4.40 – 8.60	5.40 – 8.80	p = 0.021^*
Mean ± SD	6.73 ± 0.88	7.24 ± 0.96
Median	6.90	7.15
Albumin
Min.-max.	1.60 – 4.50	1.50 – 3.50	p = 0.392
Mean ± SD	2.61 ± 0.64	2.42 ± 0.42
Median	2.50	2.45
GGT
Min.-max.	6.30 – 208.0	14.0 – 479.0	p = 0.043^*
Mean ± SD	43.69 ± 37.44	76.77 ± 90.83
Median	33.0	37.0
ALP
Min.-max.	47.0 – 522.0	52.0 – 333.0	p = 0.041^*
Mean ± SD	110.91 ± 81.84	145.30 ± 82.21
Median	87.0	128.0

Group I= Patients with liver cirrhosis, Group II= Patients with liver cirrhosis and hepatocellular carcinoma ALT= alanine aminotransferase AST= aspartate aminotransferase

GGT= gamma glutamyl transpeptidase, ALP- alkaline phosphatase

Table 3 Haematological investigations in both patients groups

	Group I (n=45)	Group II (n=30)	Test of sig
HB (g/dl)
Min.-max	5.80 – 13.20	6.90 – 14.50	P=0.685
Mean±SD	10.07±1.79	9.89±1.91
Median	9.80	9.55
WBCs x10^3
Min-max	1.16-15.80	1.90-13.27	P= 0.516
Mean±SD	5.51±2.92	5.29±2.90
Median	4.76	4.11
Platelets x10^3
Min-max	35.0-255.0	35.0-209.0	P=0.036^*
Mean±SD	130.80±60.1	100.07±47.08
Median	131.0	92.0
APRI score
Min-max	0.17-2.83	0.32-5.29	P <0.001^*
Mean±SD	1.08±0.77	2.29±1.48
Median	0.82	2.07
Proth activity
Min-max	26.10-92.30	23.30-91.30	P=0.665
Mean±SD	52.17±15.05	53.51±16.30
Median	49.10	50.60
INR
Min-max	1.04-2.50	1.06-3.20	P=0.664
Mean±SD	1.62±0.38	1.62±0.46
Median	1.60	1.54

Group I= Patients with liver cirrhosis

Group II = Patients with liver cirrhosis and hepatocellular carcinoma

Hb = haemoglobin level

NR = international normalized ratio

APRI = aspartate aminotransferase - to-platelet ratio index

* : Statistically significant at p ⩽ 0.05

Table 4 AFP and serotonin concentration in control and patients groups

	Control (n=10)	Group I (n=45)	Group II (n=30)	P value
AFP (ng/ml)
Min-Max	2.0-10.0	1.58-63.90	22.70-10271.0	P1=0.022*
Mean±SD	5.73±3.03	15.89±17.30	1406.96±2213.02	P2<0.001*
Median	5.10	10.30	462.0	P3<0.001*
Serotonin(ng/ml)
Min-Max	42.50-75.0	44.90-337.40	266.60-1577.40	P1<0.001*
Mean±SD	55.60±12.36	148.22±75.77	652.86±343.56	P2<0.001*
Median	51.50	119.40	478.35	P<0.001*

Group I= Patients with liver cirrhosis Group II= Patients with liver cirrhosis and hepatocellular carcinoma AFP= α fetoprotein

Table 5 Relation between child class and serotonin in total patients

	Child class			p
	A (n = 9)	B (n = 40)	C (n = 26)
Serotonin
Median(min.-max.)	172.10(81.10-311.10)	196.05(44.90-1317.70)	365.25(49.10-1577.40)	0.023^*
Mean ± SD	167.53±71.99	297.09±283.39	463.63±393.42

p: p value for Kruskal Wallis test

* Statistically significant at p ⩽ 0.05

Table 6 Correlation between AFP and serotonin

		Serotonin
		Control	Group I	Group II
AFP	rs	0.442	0.298^*	0.468^*
	P	0.200	0.047	0.009

Group I= Patients with liver cirrhosis

Group II= Patients with liver cirrhosis and hepatocellular carcinoma

AFP= α fetoprotein

r_s: Spearman coefficient

* : Statistically significant at p ⩽ 0.05

Table 7 Correlation between serotonin and APRI

		Serotonin
		Group I	Group II
APRI	rs	0.064	-0.363*
	P	0.675	0.049

Group I= Patients with liver cirrhosis

Group II= Patients with liver cirrhosis and hepatocellular carcinoma

APRI= aspartate aminotransferase – to-platelet ratio index

Table 8 Agreement (sensitivity, specificity and accuracy) for AFP and serotonin in liver Cirrhosis and HCC group.

		Control	Liver Cirrhosis + HCC	Sensitivity	Specificity	PPV	NPV	Accuracy
AFP	>10	10	2	93.33	100.0	100.0	83.33	95.0
	⩽10	0	28
Serotonin	>75	10	0	100.0	100.0	100.0	100.0	100.0