Cytokinome profile evaluation in patients with hepatitis C virus infection

Table 1 Differences in the serum levels of pro-inflammatory molecules between patients with either hepatitis C virus orliver cirrhosis and the healthy controls

	Controls vs HCV	Controls vs LC
IL-1α	a↑	b↑
IL-1β	b↑	b↑
IL-2R	a↑	b↑
IL-6	b↑	b↑
IL-8	b↑	b↑
CXCL1	b↑	b↑
CXCL9	b↑	b↑
CXCL10	b↑	b↑
CXCL12	a↑	a↑
MIF	a↑	b↑
β-NGF	b↑	b↑
HGF		b↑

P values obtained for all significant molecules in chronic hepatitis C virus (HCV) and HCV-related cirrhosis (LC) patients with respect to controls using the nonparametric Mann-Whitney U test. ^aP value < 0.05, ^bP < 0.01, up arrows indicate an increase in patients’ cytokine serum level vs healthy controls. HCV: Hepatitis C virus; LC: Liver cirrhosis; IL: Interleukin; NGF: Nerve growth factor; HGF: Hepatocyte growth factor; MIF: Migration inhibitory factor.

Table 2 Comparison of cytokine serum levels in all patients and healthy controls

Cytokines	Controls vs CHD	Controls vs LC	Controls vs LCD
Adiponectin	a↑	a↑	a↑
Adipsin	a↑	a↑	a↑
C-peptide	b↑	b↑	b↑
CXCL1	b↑	b↑	b↑
CXCL9	b↑	b↑	b↑
Ghrelin	a↓	a↓	a↓
GIP	a↑	a↑	a↑
Glucagon	a↑		b↑
HGF	b↑	b↑	b↑
IL-12	b↑	b↑	b↑
IL-18	b↑	b↑	b↑
IL-1α	b↑	b↑	b↑
IL-2R	b↑	b↑	b↑
Insulin	b↑	b↑	b↑
Leptin	b↑	b↑	b↑
MIF	b↑	b↑	b↑
PAI-1	b↑	b↑	b↑
Resistin	a↑	a↑	a↑
β-NGF	b↑	b↑	b↑

P values obtained for all significant molecules in patients with (1) HCV hepatitis and type 2 diabetes (CHD); (2) with HCV-related LC, and (3) with HCV-related cirrhosis and type 2 diabetes (LCD), with respect to healthy control subjects, were calculated using the nonparametric Mann-Whitney U test. ^aP value < 0.05, ^bP < 0.01; up- and down-arrows indicate if the pro-inflammatory molecule serum concentrations in patient groups increased/decreased vs healthy controls. HCV: Hepatitis C virus; LC: Liver cirrhosis; IL: Interleukin; NGF: Nerve growth factor; HGF: Hepatocyte growth factor; MIF: Migration inhibitory factor; PAI: Plasminogen activator inhibitor.

Table 3 Comparison of serum levels of significant cytokines between patients with live cirrhosis and patients with hepatocellular carcinoma

Cytokines	LC vs HCC
Adiponectin	b↓
Adipsin	a↓
CXCL12	a↑
Ghrelin	b↑
HGF	a↑
IL-16	b↑
IL-18	a↑
IL-2R	b↑
PECAM-1	a↑
Prolactin	a↑
sHER-2/neu	a↑
sIL-6Ra	a↑

P value was calculated using Mann-Whitney U test. ^aP value < 0.05, ^bP < 0.01, Up- and down-arrows indicate an increase/decrease in the serum concentrations in patient groups vs healthy controls. HCC:Hepatocellular carcinoma; LC: Liver cirrhosis; IL: Interleukin; HGF: Hepatocyte growth factor.

Table 4 List of cytokines with significantly different serum levels between liver cirrhosis and hepatocellular carcinoma patients, and the pathways in which they play important roles

Ingenuity canonical pathways	Molecules
T helper cell differentiation	IL-18, IL-6R, IL-2RA
Role of macrophages, fibroblasts, and endothelial	IL16, IL-18, IL-6R, CXCL12
Hepatic fibrosis/hepatic stellate cell activation	LEP, HGF, IL-6R
Leptin signaling in obesity	LEP, GHRL
IL-6 Signaling	IL-18, IL-6R
AMPK Signaling	LEP, ADIPOQ
Hepatic cholestasis	IL-18, GCG
Acute phase response signaling	IL-18, IL-6R
Role of cytokines in mediating communication between immune cells	IL-18
IL-2 signaling	IL-2RA
ErbB2-ErbB3 signaling	ERBB2
Role of JAK1 and JAK3 in cytokine signaling	IL-2RA
Chemokine signaling	CXCL12
HGF Signaling	HGF
Type II diabetes mellitus signaling	ADIPOQ
p38 MAPK signaling	IL-18
LXR/RXR activation	IL-18
CXCR4 signaling	CXCL12
NF-κB signaling	IL-18

LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; HGF: Hepatocyte growth factor.