Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

Table 1 Clinical features of the study population

Feature	CHB, n = 64			Healthy donors, n = 37
	Treatment naïve, n = 52	ETV treated, n = 12	P1 value	Healthy adults, n = 24	Healthy children, n = 13	P2 value	P3 value
Age in yr	43.23 ± 11.15	42.42 ± 11.27	0.821	45.58 ± 11.29	4.85 ± 3.71	< 0.001	0.397
Sex, male, as n (%)	37 (71.15)	7 (58.33)	0.388	15 (62.50)	9 (69.23)	0.682	0.451
ALT in U/L	303.61 ± 511.12	28.09 ± 12.51	< 0.001	38.77 ± 9.48	13.05 ± 4.28	< 0.001	< 0.001
AST in U/L	176.37 ± 269.94	27.37 ± 24.17	< 0.001	26.98 ± 7.12	32.88 ± 8.63	0.057	< 0.001
GGT in U/L	136.863 ± 274.897	33.700 ± 33.330	0.002	24.059 ± 24.006	9.462 ± 2.218	0.303	< 0.001
ALP in U/L	91.877 ± 33.706	66.320 ± 16.710	0.006	68.109 ± 21.576	249.692 ± 61.245	0.003	0.002
TBIL in μmol/L	46.09 ± 88.60	16.78 ± 10.85	0.294	13.45 ± 5.91	5.91 ± 3.63	0.002	0.047
BUN in mmol/L	5.70 ± 1.84	-	-	5.46 ± 1.45	3.94 ± 0.68	< 0.001	0.764
SCr in μmol/L	66.50 ± 19.72	-	-	57.36 ± 13.08	29.47 ± 11.08	< 0.001	0.042
HBsAg in IU/mL	10921.33 ± 17128.93	4024.78 ± 3602.66	0.460	-	-	-	-
HBV DNA as log10 IU/mL	5.74 ± 1.98	1.28 ± 0.68	< 0.001	-	-	-	-
HBeAg, positive, as n (%)	29 (55.77)	5 (41.67)	0.378	-	-	-	-
TC in mmol/L	4.055 ± 1.100	-	-	-	-	-	-
TG in mmol/L	1.40 ± 0.84	-	-	-	-	-	-
HDL in mmol/L	1.26 ± 0.52	-	-	-	-	-	-
LDL in mmol/L	2.38 ± 0.79	-	-	-	-	-	-
IFNα in pg/mL	60.60 ± 39.43	75.23 ± 33.69	0.115	-	-	-	-
IFNγ in pg/mL	18.25 ± 19.46	15.86 ± 7.56	0.389	-	-	-	-
IL-12 in pg/mL	13.80 ± 11.01	15.97 ± 7.01	0.247	-	-	-	-
IP-10 in pg/mL	3523.89 ± 3095.67	892.17 ± 4396.24	0.001	-	-	-	-
TNFα in pg/mL	40.68 ± 19.13	26.08 ± 11.41	0.005	-	-	-	-

The P value is based on the statistical analysis by the Mann-Whitney U test or unpaired t test according to the characteristics of the data assessing overall group differences and comes from the chronic hepatitis B group and healthy adult group. P1, P2, and P3 values separately denote the significance of comparisons between the treatment-naïve group and Entecavir-treated group, healthy adult group and healthy children group, as well as the treatment-naïve group and healthy adult group. ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; CHB: Chronic hepatitis B; ETV: Entecavir; FBG: Fasting blood glucose; GGT: γ-Glutamyl transpeptidase; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; SCr: Serum creatinine; TBIL: Total bilirubin; TC: Total cholesterol; TG: Triglyceride.

Table 2 Correlation between clinical features and the level of soluble 4-1BB

	s4-1BB
	r	P value
HBsAg in IU/mL	0.748	< 0.001
HBV DNA as log10 IU/mL	0.406	0.004
HBeAg in s/co	0.356	0.019
ALT in U/L	0.234	0.102
AST in U/L	0.165	0.246
GGT in U/L	0.076	0.595
ALP in U/L	-0.065	0.651
TBIL in µmol/L	0.063	0.662
BUN in mmol/L	-0.075	0.623
SCr in µmol/L	-0.226	0.135
WBC as × 109/L	-0.171	0.229
HGB in g/L	-0.063	0.662
PLT as × 109/L	-0.150	0.293
INR	0.344	0.014
PTA, %	-0.353	0.012
FBG in mmol/L	-0.002	0.988
TC in mmol/L	-0.350	0.050
TG in mmol/L	-0.469	0.007
HDL in mmol/L	0.148	0.481
LDL in mmol/L	-0.360	0.077
IFNα in pg/mL	-0.282	0.146
IFNγ in pg/mL	-0.314	0.104
IL-12 in pg/mL	-0.076	0.702
IP-10 in pg/mL	0.154	0.434
TNFα in pg/mL	-0.031	0.874

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; BUN: Blood urea nitrogen; FBG: Fasting blood glucose; GGT: γ-Glutamyl transpeptidase; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HDL: High-density lipoprotein; HGB: Hemoglobin; INR: International normalized ratio; LDL: Low-density lipoprotein; PLT: Platelet; PTA: Plasma thromboplastin antecedent; s4-1BB: Soluble 4-1BB; SCr: Serum creatinine; TBIL: Total bilirubin; TC: Total cholesterol; TG: Triglyceride; WBC: White blood cell.