Liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients

Table 1 Correlation between clinicopathological characteristics and serum alanine aminotransferase, alanine aminotransferase, bilirubin, albumin, plasma DNA, or hepatitis B virus DNA levels in the 350 healthy controls and 313 patients

Group	Number of cases	Serum ALT (U/L)	P	Bilirubin (μM)	P	Plasma DNA (ng/mL)	P	HBV DNA (IU/mL)	P	Serum AST (U/L)	P	Albumin(g/L)	P
Healthy controls	350	19.1 (15.1)				25.5 (17.6)		0.0 (0.0)		16.4 (14.3)		46.0 (22.2)
Sex			< 0.01		0.865		< 0.01		---		< 0.01		0.062
Male	250	22.3 (14.1)		10.6 (5.8)		30.0 (16.1)		0.0 (0.0)		19.6 (14.1)		46.4 (20.8)
Female	100	12.6 (7.6)		10.2 (5.5)		16.7 (8.1)		0.0 (0.0)		10.1 (5.5)		45.5 (20.1)
Age (yr)			0.819		0.833		0.056		---		0.916		0.066
< 36	175	18.9 (17.9)		9.7 (5.4)		23.6 (16.4)		0.0 (0.0)		16.0 (15.9)		47.6 (20.3)
≥ 36	175	19.8 (13.7)		10.5 (5.7)		26.8 (19.3)		0.0 (0.0)		16.7 (12.2)		45.8 (23.4)
HBsAb			0.263		0.439		0.060		---		0.549		0.884
Nega-tive	166	18.7 (15.1)		10.3 (5.6)		27.3 (19.1)		0.0 (0.0)		15.8 (15.1)		45.7 (22.5)
Positive	184	19.1 (15.0)		10.3 (5.6)		24.2 (16.0)		0.0 (0.0)		16.5 (15.2)		46.2 (21.6)
Drink-ing history			< 0.01		0.002		0.000		---		0.000		0.711
No	278	18.6 (12.1)		10.4 (5.7)		22.8 (15.5)		0.0 (0.0)		15.8 (11.1)		46.1 (20.9)
Yes	72	34.1 (29.2)		21.0 (19.2)		38.3 (19.0)		0.0 (0.0)		33.5 (27.4)		45.4 (23.7)
Hepati-tis B patients	313	103.3 (118.5)	< 0.011	85.6 (77.2)	0.0001	132.9 (253.7)	< 0.011	6.1 (2.9)	< 0.011	97.0 (101.6)	< 0.011	42.7 (31.2)	< 0.011
Sex			0.972		0.606		0.772		0.149		0.656		0.761
Male	224	101.4 (114.4)		88.3 (91.6)		134.2 (260.2)		6.2 (2.7)		95.3 (99.5)		42.4 (32.7)
Female	89	113.5 (143.8)		82.9 (89.1)		132.2 (170.7)		5.6 (2.8)		101.7 (116.6)		43.0 (33.2)
Age (yr)			0.011		0.221		0.312		< 0.01		0.831		0.591
< 36	155	89.2 (120.0)		86.3 (90.4)		135.9 (256.6)		6.7 (3.0)		96.5 (98.3)		42.2 (30.4)
≥ 36	158	115.9 (124.9)		83.9 (91.5)		115.8 (244.5)		5.6 (2.6)		97.8 (103.2)		43.1 (29.7)
HBeAg			0.236		0.173		0.833		< 0.01		0.742		0.070
Nega-tive	159	109.7 (126.6)		84.4 (89.4)		126.3 (294.0)		5.4 (3.1)		97.7 (101.8)		43.3 (32.5)
Positive	154	101.4 (117.0)		86.1 (90.7)		135.7 (228.9)		6.5 (2.3)		97.4 (99.6)		40.6 (34.6)
Drink-ing history			0.487		0.577		0.574		0.200		0.433		0.654
No	187	107.0 (122.8)		85.0 (87.3)		126.3 (255.4)		6.2 (2.7)		95.8 (98.5)		42.0 (30.8)
Yes	126	100.6 (118.0)		86.9 (90.3)		142.8 (243.6)		6.0 (3.0)		98.3 (100.1)		43.2 (30.7)

¹Compared with the healthy controls. All continuous data are expressed as medians (interquartile range). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBV: hepatitis B virus; HBsAb: Hepatitis B surface antibody; HBeAg: Hepatitis B E-antigen.

Table 2 Serum alanine aminotransferase, alanine aminotransferase, bilirubin, albumin, plasma DNA, and serum hepatitis B virus DNA levels in different patient groups

Group	Number of cases	Serum ALT (U/L)	P	Bilirubin (μM)	P	Plasma DNA (ng/mL)	P	HBV DNA (IU/mL)	P	Serum AST (U/L)	P	Albumin(g/L)	P
Healthy controls	350	19.1 (15.1)				25.5 (17.6)		0.0 (0.0)		16.4 (14.3)		46.0 (22.2)
Acute HBV infec-tion	50	213.8 (355.9)		121.6 (207.0)		336.8 (179.5)		5.5 (2.4)		197.6 (312.5)		45.4 (24.6)
Chronic HBV infec-tion	263	88.3 (98.0)	< 0.011	73.9 (88.3)	< 0.011	106.4 (174.1)	< 0.011	6.2 (2.9)	0.059*	90.6 (93.7)	< 0.011	40.2 (41.3)	0.0041
Inflamma-tion			< 0.01		< 0.01		< 0.01		0.893		< 0.01		0.444
Mild	68	59.9 (41.5)		30.6 (31.4)		46.9 (29.5)		5.7 (2.5)		51.2 (50.6)		41.7 (28.6)
Modera-te	70	62.8 (68.0)		45.4 (50.4)		106.1 (127.2)		6.4 (3.1)		61.3 (72.9)		40.9 (30.4)
Marked	83	152.8 (114.7)		130 (125.5)		141.1 (77.4)		5.8 (2.8)		153.2 (160.8)		39.5 (32.6)
Severe	42	99.9 (148.0)		228 (254.9)		862.5 (1213.6)		6.8 (2.8)		91.7 (135.1)		39.8 (33.2)
Fibrosis			0.552		0.015		< 0.01		0.060		0.121		0.606
No cirrhosis	212	88.0 (106.4)		65.2 (58.2)		131.0 (235.8)		6.3 (3.1)		87.0 (93.0)		40.8 (38.6)
Stage 0	59	83.5 (98.6)		71.9 (70.3)		111.8 (477.0)		6.6 (3.0)		87.7 (91.6)		41.6 (38.5)
Stage 1	72	96.6 (81.2)		60.2 (66.7)		179.6 (235.3)		6.5 (3.0)		88.4 (90.3)		40.1 (38.3)
Stage 2	46	87.4 (89.0)		64.8 (79.6)		98.8 (90.1)		6.0 (2.7)		79.1 (82.5)		40.1 (38.7)
Stage 3	35	91.7 (110.3)		77.7 (72.4)		87.2 (77.7)		6.0 (2.7)		84.6 (88.0)		40.2 (39.9)
Cirrho-sis (Stage 4)	51	91.4 (73.5)		92.0 (99.4)		73.1 (44.8)		5.7 (2.1)		91.9 (94.5)		39.9 (43.8)

¹Compared with the acute hepatitis B virus infection patients. All continuous data are expressed as medians (interquartile range). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBV: Hepatitis B virus.