Type 2 diabetes mellitus characteristics affect hepatocellular carcinoma development in chronic hepatitis B patients with cirrhosis

Table 1 Baseline characteristics of the patients

Characteristic	T2DM at baseline, n = 196	Non-T2DM at baseline, n = 216	P value
Age in yr	55 (50-62)	54 (49-62)	0.090
Female sex	69 (35.2)	72 (33.3)	0.690
Smoking status	98 (50.0)	125 (57.9)	0.114
Alcohol abuse status	76 (38.8)	74 (34.3)	0.358
Dyslipidemia	64 (32.7)	58 (26.9)	0.235
Ascites	9 (4.6)	15 (6.9)	0.400
Esophagogastric varices	6 (3.1)	12 (5.6)	0.238
PT	10.4 (9.6-11.3)	11.8 (10.8-14.1)	< 0.001
INR	0.94 (0.87-1.01)	1.05 (0.96-1.24)	< 0.001
AST in IU/mL	25 (20-38)	27 (20-45)	0.389
ALT in IU/mL	26 (19-34)	28 (20-44)	0.101
Platelet count as × 109/ L	177 (132-203)	161 (112-207)	0.105
AFP in ng/mL	1.24 (0.56-20.83)	2.36 (1.53-25.00)	0.761
GGT in U/L	29 (17-58)	33 (19-80)	0.062
Total bilirubin in μmol/L	15.0 (10.5-18.5)	15.1 (11.1-24.9)	0.096
Albumin in g/L	39.7 (33.1-42.8)	37.8 (32.3-41.0)	0.090
MELD score	6 (5-8)	6 (5-10)	0.191
HBsAg in log IU/mL	2.50 (1.91-2.68)	2.64 (2.22-2.69)	0.104
HBV DNA in IU/mL	19500 (1260-234000)	23850 (8738-329000)	0.936
Creatinine in µmol/L	60 (52-74)	61 (50-74)	0.379
HBeAg positivity	50 (25.5)	56 (24.1)	0.727
Antiviral treatment	137 (69.9)	144 (66.7)	0.526
Duration of T2DM in yr
0-2.0	44 (22.4)
2.1-5.0	42 (21.4)
5.1-10.0	52 (26.5)
> 10.0	58 (29.6)
T2DM treatment
Metformin ± sulfonylurea	112 (57.1)
Insulin ± sulfonylurea	50 (25.5)
Diet alone	34 (17.3)

AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; HBeAg: Hepatitis B e-antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; INR: International normalized ratio; MELD: Model for end-stage liver disease; PT: Prothrombin time; T2DM: Type 2 diabetes mellitus.

Table 2 Cox regression analysis of factors related to hepatocarcinogenesis in the patients

Variable	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age in yr, > 65 vs ≤ 65	1.16 (0.63, 2.10)	0.649	1.38 (0.62, 3.11)	0.434
Sex, male vs female	4.37 (1.98, 9.64)	< 0.001	3.47 (1.36, 8.89)	0.010
Smoking status, yes vs no	1.97 (1.15, 3.38)	0.013	1.46 (0.61, 3.45)	0.394
Alcohol abuse status, yes vs no	1.83 (0.44, 2.55)	0.558	1.38 (0.80, 1.68)	0.008
Dyslipidemia, yes vs no	1.58 (0.30, 2.09)	0.090	0.80 (0.36, 1.79)	0.589
Diabetes mellitus, yes vs no	2.54 (1.41, 4.59)	0.002	6.73 (2.77, 16.36)	< 0.001
Ascites, yes vs no	2.68 (1.20, 5.98)	0.016	1.41 (0.31, 6.43)	0.660
Esophagogastric varices, yes vs no	1.20 (0.37, 3.87)	0.766	0.62 (0.13, 2.97)	0.552
AFP in ng/mL, > 20 vs ≤ 20	1.85 (0.98, 3.51)	0.059	3.89 (1.06, 14.27)	0.041
γ-GTP in U/L, per SD	1.24 (0.52, 2.14)	0.692	1.34 (0.75, 3.21)	0.530
HBsAg, > 2.0 log IU/mL vs ≤ 2.0 log IU/mL	1.74 (0.43, 2.28)	0.277	4.10 (1.52, 11.12)	0.005
HBV DNA, ≤ 20000 IU/mL vs > 20000 IU/mL	0.46 (0.20, 1.07)	0.072	1.09 (0.38, 3.15)	0.877
HBeAg positivity, yes vs no	0.59 (0.28, 1.28)	0.181	0.54 (0.20, 1.49)	0.236
Antiviral treatment, yes vs no	0.27 (0.16, 2.14)	0.365	0.74 (0.33, 1.67)	0.475

AFP: Alpha-fetoprotein; CI: Confidence interval; HBeAg: Hepatitis B e-antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HR: Hazard ratio; AFP: Alpha-fetoprotein; GTP: Guanosine triphosphate; HR: Hazard ratio.

Table 3 Factors correlated with hepatocarcinogenesis in the type 2 diabetes mellitus group

Variable	HR	95%CI	P value
Age > 65 yr	23.54	4.59-120.74	< 0.001
Male sex	3.64	1.01-13.20	0.049
Smoking	3.10	0.85-11.38	0.088
Alcohol abuse	0.38	0.11-1.31	0.125
Dyslipidemia	1.56	0.50-4.85	0.440
Ascites	0.50	0.07-3.60	0.489
Esophagogastric varices	0.54	0.05-6.34	0.623
AFP > 20 ng/mL	17.44	2.86-106.23	0.002
γ-GTP in U/L, per SD	2.31	1.55-14.01	0.762
HBsAg > 2.0 log IU/mL	11.93	2.82-50.41	0.001
HBV DNA > 20000 IU/mL	0.39	0.09-1.60	0.190
HBeAg positivity	0.96	0.29-3.11	0.941
Antiviral treatment	0.19	0.06-0.64	0.007
T2DM duration in yr
≤ 5	-	-	-
> 5	6.74	2.36-19.29	< 0.001
T2DM therapy
Yes/metformin ± sulfonylurea	-	-	-
Yes/insulin ± sulfonylurea	1.45	0.26-7.96	0.041
Yes/diet control only	10.70	2.91-39.31	< 0.001

AFP: Alpha-fetoprotein; CI: Confidence interval; HBeAg: Hepatitis B e-antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HR: Hazard ratio; T2DM: Type 2 diabetes mellitus; GTP: Glutamyltranspeptidase; AFP: Alpha-fetoprotein.