Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B

Table 1 Clinical characteristics of participants in validation

Group	CHB	NASH	Ctrl
Individuals (n)	24	20	24
Gender (n)
Male	21	17	19
Female	3	3	5
Age (yr)	37.6 ± 9.0	39.4 ± 9.6	35.6 ± 10.2
ALT (IU/L)	82.6 (14-412)	51.7 (18-203)	21.5 (14-43)
AST (IU/L)	62.6 (9-206)	31.55 (17-62)	21.4 (16-49)
GGT (IU/L)	69.4 (10-580)	45.8 (13-124)	20.8 (12-33)
ALP (IU/L)	95.8 (51-211)	66.0 (41-90)	62.3 (42-96)
TBIL (μmol/L)	19.2 (10.2-50.7)	19.5 (13.1-31.7)	15.9 (6.9-27.1)
HBV DNA	7 377 395 (0-94 800 000)	0	0
Bile acid (μmol/L)	6.9 (1.4-13)	17.9 (3-118.7)	8.4 (4.1-12)
HBV status (n)
HBsAg+	24	0	0
HBsAg-	0	20	24

Bile acid were given as medians (range). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: γ-glutamyltransferase; ALP: Alkaline phosphatase; TBIL: Total bilirubinand; CHB: Chronic hepatitis B; NASH: Nonalcohlic steatohepatitis; Ctrl: Healthy donor; HBsAg: Hepatitis B surface antigen.

Table 2 Differentially expressed miRNAs in chronic hepatitis B patients and healthy donors

miRNA	Fold change	P value	CHB (log2) mean	Ctrls (log2) mean
hsa-miR-122	8.29	2.99E-03	8.14	5.09
hsa-miR-138	4.23	5.69E-03	2.68	0.60
hsa-miR-638	4.18	2.43E-03	12.62	10.55
hsv1-miR-H1	3.93	7.92E-03	7.67	5.70
hsa-miR-575	3.67	5.69E-03	9.59	7.71
hsa-miR-572	3.36	3.98E-03	7.58	5.83
kshv-miR-K12-3	3.34	2.60E-03	10.19	8.45
hsa-miR-1915	3.12	5.22E-03	11.30	9.66
hsa-miR-623	3.07	4.69E-03	6.85	5.23
hsa-miR-1268	2.81	6.43E-03	9.94	8.45
hsa-miR-939	2.63	3.94E-03	8.81	7.42
hsa-miR-498	2.29	4.30E-03	6.07	4.87
hsa-miR-421	0.37	4.05E-03	0.93	2.38
hsa-miR-598	0.35	5.24E-04	0.67	2.20
hsa-miR-155	0.34	6.40E-03	2.40	3.94
hsa-miR-424	0.33	9.76E-03	3.67	5.26
hsa-miR-23b	0.28	8.42E-03	5.44	7.29
hsa-miR-195	0.27	1.17E-03	1.20	3.10
hsa-miR-487b	0.26	5.46E-03	1.49	3.44
hsa-miR-224	0.25	3.71E-03	1.45	3.45
hsa-miR-495	0.24	2.50E-03	1.16	3.21
hsa-miR-181c	0.22	6.78E-03	1.88	4.03
hsa-miR-654-3p	0.21	8.27E-03	1.99	4.22
hsa-let-7e	0.21	2.52E-03	0.75	2.99
hsa-miR-382	0.21	9.11E-03	1.78	4.02
hsa-miR-171	0.19	9.66E-03	2.47	4.89
hsa-miR-128	0.18	6.17E-03	2.38	4.82
hsa-miR-625	0.18	2.70E-04	2.14	4.61
hsa-miR-30e1	0.16	2.94E-03	1.89	4.51
hsa-miR-139-5p	0.16	3.10E-03	2.39	5.03
hsa-miR-30c	0.16	8.92E-03	3.66	6.32
hsa-miR-744	0.15	9.63E-03	2.40	5.10
hsa-miR-374b	0.12	3.05E-03	2.35	5.44
hsa-miR-376c	0.11	4.32E-03	2.91	6.04

¹MicroRNA (miRNA) cloning studies sometimes identify two about 22 nt sequences miRNAs which originate from the same predicted precursor. When the relative abundancies clearly indicate which is the predominantly expressed miRNA, the mature sequences are assigned names of the form miRNA (the predominant product) and miRNA* (from the opposite arm of the precursor). For example, miR-123 and miR-123* would share a pre-miRNA hairpin, but more miR-123 would be found in the cell. In the past, this distinction was also made with "s" (sense) and "as" (antisense). CHB: Chronic hepatitis B; Ctrl: Healthy donor.

Table 3 Coefficient of Spearman correlation between microRNA variables and liver function parameter variables (all 68 samples)

Variables	miR-122	miR-638	miR-572	miR-575	miR-744
miR-122	1.000	0.757b	0.780b	0.614b	-0.669b
miR-638	0.757b	1.000	0.876b	0.822b	-0.733b
miR-572	0.780b	0.876b	1.000	0.794b	-0.639b
miR-575	0.614b	0.822b	0.794b	1.000	-0.570b
miR-744	-0.669b	-0.733b	-0.639b	-0.570b	1.000
ALT	0.559d	0.431d	0.375d	0.299c	-0.413d
AST	0.692d	0.474d	0.465d	0.324d	-0.434d
GGT	0.421d	0.371d	0.280c	0.214	-0.355d
ALP	0.358d	0.312d	0.320d	0.306c	-0.180
TBIL	0.034	0.041	-0.114	-0.074	-0.068
Bile acid	0.068	-0.020	0.008	-0.023	0.090

^bP < 0.01 microRNA (miRNA) vs miRNA without superscript b in the same column (2-tailed test);

^cP < 0.05 level miRNA vs liver function parameter (2-tailed test);

^dP < 0.01 level miRNA vs liver function parameter (2-tailed test). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: γ-glutamyltransferase; ALP: Alkaline phosphatase; TBIL: Total bilirubin and bile.