Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C

doi:10.3748/wjg.v20.i30.10449

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World Journal of Gastroenterology

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World J Gastroenterol. Aug 14, 2014; 20(30): 10449-10456
Published online Aug 14, 2014. doi: 10.3748/wjg.v20.i30.10449

Table 1 Characteristics of the study population

	HCV			Healthy subjects			Pvalue
	Median	LQ-UQ	Min-Max	Median	LQ-UQ	Min-Max	Pvalue
Age	32	23-48	18-61	32	23-48	26-56	P > 0.05
BMI	23.6	23.2-24.7	20.1-24.9	23.3	22.4-24.7	19.5-24.9	P > 0.05
ALT U/L	52	43-79	23-339
HCV viremia (IU/mL)	1230000	382000-3880000	112000-8950000
SOCS-3	5.17	2.09-9.78	0.5-24.53
HOMA	2.24	1.50-3.36	0.78-9.67	0.56	0.34-1.02	0.25-2	P = 0.0003
Visfatin (ng/mL)	2.64	1.17-3.58	0.45-9.37	2.75	2.47-3.8	1.26-5.27	P > 0.05
Omentin (ng/mL)	385.07	340.33-522.77	115.7-757.34	375.55	278.02-477.33	115.68-587.51	P > 0.05
Adiponectin (µg/mL)	7.23	5.48-8.72	3.51-18.48	9.335	6.275-11.20	5.89-15.33	P > 0.05
Resistin (ng/mL)	1.54	1.11-1.74	0.73-2.92	1.48	1.31-1.71	1.04-2.7	P > 0.05
Leptin (ng/mL)	4.85	2.425-13.6	0.77-54.65	5.785	3.81-17.06	1.85-42.76	P > 0.05
Osteopontin (ng/mL)	28.71	18.06-36.19	5.33-59.15	20.56	15.47-21.2	6.14-32.42	P > 0.05
	Number of patients (n)			Number of patients (n)
Age > 40	9			4			P > 0.05
Age < 40	22			5			P > 0.05
Women	10			4			P > 0.05
Men	21			5			P > 0.05

The mean HOMA-IR index in HCV infected patients was significantly higher compared to healthy controls (2.24 vs 0.59, P = 0.0003) (Table 1). However, there was no significant difference in adipocytokine concentration between patients with chronic hepatitis C and healthy subjects. LQ: Lower quartile; UQ: Upper quartile; BMI: Body mass index; ALT: Alanine aminotransferase; HCV: Hepatitis C virus; SOCS-3: Suppressor of cytokine signaling 3; HOMA: Homeostasis model assessment.

Table 2 Adipokines and homeostasis model assessment of insulin resistance in chronic hepatitis C

	Median (LQ-UQ)		Pvalue
	HOMA-IR > 2.5 (n= 15)	HOMA-IR < 2.5 (n= 16)
Omentin (ng/mL)	381.24 (332.79- 483.33)	399.91 (367.16-541.72)	Pvalue	P > 0.05
Adiponectin (μg/mL)	6.24 (5.48-7.92)	8.37 (5.63-12.18)	P > 0.05
Resistin (ng/mL)	1.56 (1.42-1.74)	1.24 (1.03-1.56)	P > 0.05
Leptin (ng/mL)	6.79 (2.34-13.11)	3.04 (2.51-17.2)	P > 0.05
Visfatin (ng/mL)	2.66 (1.09-3.12)	2.05 (1.17-3.3)	P > 0.05
Osteopontin (ng/mL)	28.71 (15.52-37.1)	31.18 (20.29-36.07)	P > 0.05

Adipokine levels were not related to HOMA-IR index in patients with chronic hepatitis C. HOMA-IR: Homeostasis model assessment of insulin resistance; LQ: Lower quartile; UQ: Upper quartile.

Table 3 Adipokines and liver steatosis in chronic hepatitis C

	With steatosis (n= 10)		Without steatosis (n= 21)		Pvalue
	Median (LQ-UQ)	Min-max	Median (LQ-UQ)	Min-max
SOCS3	6.553 (3.393-11.777)	1.042-24.537	5.106 (2.095-8.713)	0.5-17.95	P > 0.05
HOMA	2.815 (1.99-4.84)	1.25-9.67	1.995 (1.21-2.51)	0.78-7.25	P = 0.05
Adiponectin (μg/mL)	5.985 (4.83-7.23)	3.55-8.43	8.37 (5.71-9.07)	3.51-18.48	P = 0.047
Osteopontin (ng/mL)	33.51 (15.52-49.12)	5.33-59.15	24.7 (18.26-34.58)	11.57-47.85	P > 0.05
Leptin (ng/mL)	5.705 (3.04-17.2)	2.34-54.65	3.825 (1.33-13.11)	0.77-39.04	P > 0.05
Resistin (ng/mL)	1.65 (1.42-1.84)	1.17-2.36	1.51 (1.03-1.58)	0.73-2.92	P > 0.05
Omentin (ng/mL)	374.875 (332.79-483.33)	227.99-757.34	393.92 (360.09-522.77)	115.7-735.84	P > 0.05
Visfatin (ng/mL)	2.465 (1.37-3.12)	0.45-3.97	2.64 (1.17-4.08)	0.53-9.37	P > 0.05

Hepatic steatosis was related to increased HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs 8.37, P = 0.04). SOCS-3: Suppressor of cytokine signaling 3; HOMA-IR: Homeostasis model assessment of insulin resistance; LQ: Lower quartile; UQ: Upper quartile.

Table 4 Adipokines and liver inflammation in chronic hepatitis C

	G≥2 (n= 9)		G < 2 (n= 22)		Pvalue
	Median (LQ-UQ)	Min-max	Median (LQ-UQ)	Min-max
Omentin (ng/mL)	381.24 (367.16-522.77)	115.7-757.34	389.46 (340.33-483.33)	227.99-735.84	P > 0.05
Adiponectin (μg/mL)	6.21 (5.71-7.56)	4.6-9.07	8 (5.48-9.06)	3.51-18.24	P > 0.05
Resistin (ng/mL)	1.24 (1.17-1.65)	0.91-2.36	1.55 (1.11-1.82)	0.73-2.92	P > 0.05
HOMA	2.1(1.59-3.99)	0.78-9.67	2.38 (1.25-2.84)	0.88-7.25	P > 0.05
Leptin (ng/mL)	10.83 (4.26-31.44)	1.69-54.65	3.43 (1.83-9.36)	0.77-39.04	P > 0.05
Visfatin (ng/mL)	2.05 (1.83-2.66)	0.65-8.89	2.78 (1.17-4.08)	0.45-9.37	P > 0.05
Osteopontin (ng/mL)	34.04 (32.7-36.19)	22.47-49.12	23.25 (15.05-36.07)	5.33-59.15	P = 0.03
SOCS-3	3.69 (2.67-7.05)	0.66-11.52	8.13 (1.74-11.78)	0.5-24.53	P > 0.05

Inflammatory activity (G ≥ 2) was associated with increased osteopontin concentration (34.04 vs 23.35, P = 0.03). No relationships were found between other adipokine concentrations and the grade of inflammatory activity. n: Number of patients, in liver biopsy: G: Grade of inflammation and necrosis; HOMA-IR: Homeostasis model assessment of insulin resistance; LQ: Lower quartile; UQ: Upper quartile.

Table 5 Adipokines and liver fibrosis in chronic hepatitis C

	S≥2 (n= 22)		S < 2 (n= 9)		Pvalue
	Median (LQ-UQ)	Min-max	Median (LQ-UQ)	Min-max
Omentin (ng/mL)	436.94 (367.16-538.15)	115.7-757.34	360.09 (296.34-383.55)	257.55-396.92	P = 0.03
Adiponectin (μg/mL)	7.39 (5.71-9.06)	4.6-18.48	6.46 (4.52-8.37)	3.51-11.28	P > 0.05
Resistin (ng/mL)	1.4 (1.03-1.58)	0.73-2.36	1.74 (1.54-2.67)	0.76-2.92	P = 0.047
HOMA (mmol/L)	2.1 (1.33-3.36)	0.78-9.77	2.5 (1.5-2.79)	0.88-5.17	P > 0.05
Leptin (ng/mL)	4.09 (2.51-8.56)	1.00-54.65	11.94 (1.17-21.5)	0.77-39.04	P > 0.05
Visfatin (ng/mL)	2.25 (1.17-3.3)	0.53-8.89	3.12 (1.57-5.26)	0.45-9.37	P > 0.05
Osteopontin (ng/mL)	32.84 (22.47-37.1)	8.46-59.15	20.29 (15.05-24.33)	5.33-38.46	P = 0.03
SOCS-3	4.51 (1.92-9.24)	0.66-24.53	8.61 (4.40-11.777)	0.5-17.95	P > 0.05

Advanced liver fibrosis (S ≥ 2) was more commonly observed in patients with increased serum levels of omentin and osteopontin (436.94 vs 360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration (1.40 vs 1.74, P = 0.047). Other adipokines were not related to the progression of liver fibrosis. No difference was found in HOMA-IR index according to stages of fibrosis in liver biopsy specimens. n: Number of patients; S: Stage of fibrosis; SOCS-3: Suppressor of cytokine signaling 3; HOMA-IR: Homeostasis model assessment of insulin resistance; LQ: Lower quartile; UQ: Upper quartile.

Table 6 Correlations between adipokines and hepatic expression of suppressor of cytokine signaling 3 in chronic hepatitis C

	SOCS-3	Pvalue
	Spearman’s rank correlationρ	Pvalue
Age	0.12	P > 0.05
HCV viral load (IU/mL)	0.15	P > 0.05
ALT (U/L)	0.41	P > 0.05
HOMA	0.39	P > 0.05
Adiponectin (μg/mL)	0.24	P > 0.05
Osteopontin (ng/mL)	0.30	P > 0.05
Visfatin (ng/mL)	0.23	P > 0.05
Resistin (ng/mL)	0.55	P > 0.05
Leptin (ng/mL)	0.14	P > 0.05
Omentin (ng/mL)	0.50	P > 0.05

No correlation was found between serum adipokine levels or HOMA-IR index and hepatic expression of SOCS-3. SOCS-3: Suppressor of cytokine signaling 3; HOMA-IR: Homeostasis model assessment of insulin resistance; ALT: Alanine aminotransferase.

Table 7 Adipokines and hepatitis C virus viremia

	VL≥600000 IU/mL (n= 12)		VL < 600000 IU/mL (n= 19)		Pvalue
	Median (LQ-UQ)	Min-max	Median (LQ-UQ)	Min-max
Age	32 (23-54)	18-61	32.5 (23.5-38)	18-61	P > 0.05
Adiponectin (μg/mL)	6.46 (5.48-8.72)	3.51-18.48	7.42 (5.48-8.75)	3.55-17.93	P > 0.05
Osteopontin (ng/mL)	31.18 (15.52-37.1)	11.57-59.15	26.84 (21.19-33.78)	5.33-54.98	P > 0.05
Leptin (ng/mL)	4.09 (1.59-21.5)	0.77-54.65	5.47 (2.51-13.11)	1.17-17.2	P > 0.05
Resistin (ng/mL)	1.42 (1.03-1.74)	0.73-2.92	1.56 (1.29-1.78)	0.87-2.71	P > 0.05
Omentin (ng/mL)	393.92 (342.46-534.21)	115.7-757.34	381.88 (312.96-497.43)	227.99-735.84	P > 0.05
HOMA	2.01 (1.5-3.99)	0.88-9.67	2.5 (1.25-3.36)	0.78-5.66	P > 0.05
Visfatin (ng/mL)	2.67 (1.17-3.97)	0.53-9.37	2.14 (1.23-3.11)	0.45-9.33	P > 0.05

Serum adipokine concentrations and HOMA-IR index were not found to be related to HCV viremia. VL: Viral load; SOCS-3: Suppressor of cytokine signaling 3: HOMA-IR: Homeostasis model assessment of insulin resistance; HCV: Hepatitis C virus; LQ: Lower quartile; UQ: Upper quartile.

Table 8 Adipokines and single nucleotide polymorphisms of interleukin 28B in chronic hepatitis C

	CC (n= 6)		TT/CT (n= 25)		Pvalue
	Median (LQ-UQ)	Min-max	Median (LQ-UQ)	Min-max
SOCS-3	11.52 (3.164-15.738)	2.17-17.95	5.10 (1.75-8.713)	0.5-24.537	P > 0.05
HCV viremia (IU/mL)	1195000 (362000-3830000)	112000-9850000	3780000 (799000-4290000)	382000-7210000	P > 0.05
ALT (U/L)	54 (43-83)	23-339	45 (44-47)	41-48	P > 0.05
HOMA	(1.02-3.99)	0.78-5.66	2.44 (1.5-2.84)	0.88-9.67	P > 0.05
Adiponectin (μg/mL)	7.56 (6-8.37)	5.33-9.07	6.35 (5.34-8.89)	3.51-18.48	P > 0.05
Osteopontin (ng/mL)	24.33 (22.18-32.98)	13.14-34.58	29.94 (16.79-37.78)	5.33-59.15	P > 0.05
Visfatin (ng/mL)	2.64 (1.57-6.35)	0.65-9.33	2.56 (1.13-5.69)	0.45-9.37	P > 0.05
Leptin (ng/mL)	13.11 (8.56-17.2)	5.47-39.04	3.04 (1.69-11.94)	0.77-54.65	P > 0.05
Omentin (ng/mL)	367.16 (257.55-399.91)	152.74-522.77	390.95 (341.39-536.18)	115.7-757.34	P > 0.05
Resistin (ng/mL)	1.17 (0.91-1.65)	0.76-1.74	1.55 (1.205-1.83)	0.73-2.92	P > 0.05

The single nucleotide polymorphisms (SNPs) of IL28B (rs 12979860) were not associated with adipokine levels or HOMA-IR index. Genotypes of IL28B: CC and not CC (CT and TT); SOCS-3: Suppressor of cytokine signaling 3; HOMA-IR: Homeostasis model assessment of insulin resistance; ALT: Alanine aminotransferase; LQ: Lower quartile; UQ: Upper quartile.

Citation: Wójcik K, Jabłonowska E, Omulecka A, Piekarska A. Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C. World J Gastroenterol 2014; 20(30): 10449-10456
URL: https://www.wjgnet.com/1007-9327/full/v20/i30/10449.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i30.10449