Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection

doi:10.3748/wjg.v16.i18.2265

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. May 14, 2010; 16(18): 2265-2271
Published online May 14, 2010. doi: 10.3748/wjg.v16.i18.2265

Table 1 Comparison of baseline features among HBV, HCV, dual HBV and HCV, and non-HBV, non-HCV related hepatocellular carcinoma patients

	HBV n = 63	HCV n = 59	HBV + HCV n = 15	Non-HBV, non-HCV n = 28	P value
Age (yr)¹	55 (46-66)^a^c	66 (57-75)^a^d	60 (50-68)^d	61 (55-67)^c	< 0.001
Sex (M/F)	45/18	41/18	10/5	26/2	0.093
DM (%)	8 (12.7)^a	21 (35.6)^a^e	4 (26.7)	2 (7.1)^e	0.003
BMI (kg/m²)¹	24.3 (22.2-26.8)	23.8 (21.8-26.6)	23.6 (20.9-25.5)	24.5 (23.3-26.7)	0.439
Overweight (%)	24 (38)	22 (37)	4 (27)	10 (36)	0.797
Obesity (%)	4 (6)	5 (8)	1 (7)	2 (7)	0.965
AST (U/L)¹	48 (38-71)^a	72 (39-123)^a^e	72 (47-111)	38 (29-52)^e	0.002
ALT (U/L)¹	45 (34-63)^a	63 (29-100)^a^e	82 (54-117)	27 (21-39)^e	0.011
Child–Pugh class (A/B, C)	47/16	46/13	11/4	23/5	0.857
Platelet (10⁴/μL)¹	16.5 (12.0-25.0)^a	13.2 (8.7-17.1)^a^e	12.7 (7.6-18.1)^f	21.1 (15.3-24.1)^e^f	0.001
AFP (ng/mL)¹	15 (6-525)	28 (7-256)	38 (11-4388)	15 (6-8027)	0.468
Tumor size ( ≤ 3 cm) (%)	14 (22.2)^a	29 (49.2)^a^e	7 (46.7)	5 (17.9)^e	< 0.001
BCLC ( ≤ early stage) (%)	20 (31.7)^a^b	31 (52.5)^a^e^f	9 (60.0)^b	4 (14.3)^e^f	0.001
HOMA-IR	3.5 (2.0-8.6)^a	4.4 (2.9-6.6)^a	3.2 (1.7-10.7)	3.4 (2.0-4.6)	0.108
Insulin (μU/mL)¹	12.8 (8.4-25.0)	14.8 (9.9-21.30)	11.9 (8.1-23.5)	9.7 (7.6-14.8)	0.256
Adiponectin (μg/mL)	4.7 (2.9-8.1)^a^c	7.9 (5.2-11.0)^a^e	8.0 (3.8-10.9)^f	3.7 (2.0-6.0)^c^e^f	0.002

¹Median (interquartile range); P value by one-way ANOVA test or χ² test;

^aP < 0.05 between HBV and HCV;

^bP < 0.05 between HBV and HBV + HCV;

^cP < 0.05 between HBV and non-HBV, non-HCV;

^dP < 0.05 between HCV and HBV + HCV;

^eP < 0.05 between HCV and non-HBV, non-HCV;

^fP < 0.05 between HBV + HCV and non-HBV, non-HCV HCC with LSD post-hoc correction. HBV: Hepatitis B virus; HCV: Hepatitis C virus; DM: Diabetes mellitus; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; AFP: Alpha-fetoprotein; BCLC: Barcelona clinic liver cancer; HOMA-IR: Homeostasis model assessment of insulin resistance.

Table 2 Comparison of baseline features, HOMA-IR and adiponectin level among chronic hepatitis, advanced fibrosis and HCC patients with chronic HCV infection

	Chronic hepatitis (F0-2) n = 86	Advanced fibrosis (F3-4) n = 43	Hepatocellular carcinoma n = 59	P value²
Age (yr)¹	53 (45-58)^a^b	56 (49-63)^a^c	66 (57-75)^b^c	< 0.001
Male sex (%)	44 (51)^b	17 (40)^c	41 (69)^b^c	0.008
DM (%)	13 (15)^b	12 (28)	21 (36)^b	0.016
BMI (kg/m²)¹	24.3 (21.8-26.3)	25.0 (22.0-29.4)	23.8 (21.8-26.6)	0.227
AST (U/L)¹	90 (64-122)	114 (87-178)^c	72 (39-123)^c	0.085
ALT (U/L)¹	127 (92-187)^b	140 (102-199)^c	63 (29-100)^b^c	0.001
Platelet (10⁴/μL)¹	20.2 (15.8-22.4)^a^b	13.7 (10.6-17.9)^a	13.2 (8.7-17.1)^b	< 0.001
Sugar (mg/dL)¹	91 (87-101)^b	98 (88-122)^c	114 (94-172)^b^c	< 0.001
Insulin (μU/mL)¹	10.3 (7.7-14.4)^b	11.7 (6.9-15.9)^c	14.8 (9.9-21.3)^b^c	0.003
HOMA-IR¹	3.5 (2.6-4.7)^b	4.1 (2.6-5.9)^c	4.4 (2.9-6.6)^b^c	0.018
Adiponectin (μg/mL)¹	5.0 (3.4-8.4)	5.8 (4.1-9.7)	7.9 (5.2-11.0)	0.222

¹Median (interquartile range);

²P value by one-way ANOVA test or χ² test;

^aP < 0.05 between chronic hepatitis and advanced fibrosis;

^bP < 0.05 between chronic hepatitis and hepatocellular carcinoma;

^cP < 0.05 between advanced fibrosis and hepatocellular carcinoma with LSD post-hoc correction.

Table 3 Univariate and multivariate analysis of factors associated serum adiponectin level in 188 patients with chronic HCV infection

	Univariate		Multivariate
	Coefficient	P value¹	Regression coefficient	SE	P value³
Age	0.388	< 0.001	0.140	0.028	< 0.001
Male sex²	NA	< 0.001	-2.925	0.744	< 0.001
BMI	-0.281	< 0.001	-0.495	0.101	< 0.001
HCC²	NA	0.136	-	-	-
DM²	NA	0.629	-	-	-
Child-Pugh classification	0.107	0.145	-	-	-
AST (U/L)	0.159	0.030	-	-	-
ALT (U/L)	-0.096	0.195	-	-	-
Platelet (10⁴/μL)	-0.198	0.009	-	-	-
Insulin (μU/mL)	-0.179	0.014	-	-	-
HOMA-IR	-0.290	< 0.001	-	-	-

¹P value by Spearman’s test or

²P value by Mann-Whitney U test;

³P value by stepwise linear regression analysis. NA: Not applicable.

Table 4 Stepwise logistic regression analysis of factors associated with HCC

	Comparison	OR	95% CI	P value
All patients
Age	Per 1 year increase	1.124	1.067-1.183	< 0.001
Insulin	Per 1 μU/mL increase	1.585	1.269-1.980	< 0.001
HOMA-IR	Per 1 increase	0.495	0.330-0.743	0.001
DM	Yes vs no	11.601	2.500-53.800	0.002
Sex	Male vs female	3.877	1.282-11.729	0.016
Non-DM patients
Age	Per 1 year increase	1.170	1.075-1.272	< 0.001
Insulin	Per 1 μU/mL increase	2.434	1.555-3.811	< 0.001
HOMA-IR	Per 1 increase	0.158	0.055-0.452	0.001
Sex	Male vs female	6.111	1.310-28.499	0.021

Citation: Hung CH, Wang JH, Hu TH, Chen CH, Chang KC, Yen YH, Kuo YH, Tsai MC, Lu SN, Lee CM. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol 2010; 16(18): 2265-2271
URL: https://www.wjgnet.com/1007-9327/full/v16/i18/2265.htm
DOI: https://dx.doi.org/10.3748/wjg.v16.i18.2265