Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study

doi:10.4254/wjh.v16.i5.809

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World Journal of Hepatology

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Prospective Study

World J Hepatol. May 27, 2024; 16(5): 809-821
Published online May 27, 2024. doi: 10.4254/wjh.v16.i5.809

Table 1 Etiological characteristics of 3375 acute-on-chronic liver disease patients, n (%)

Characteristic	Overall (n = 3375)	Noncirrhosis (n = 792)	Cirrhosis (n = 2853)	P value
Demographics
Sex, male	2489 (73.7)	606 (76.5)	1883 (72.9)	0.048
Age, yr (mean ± SD)	49.65 ± 12.14	42.51 ± 11.65	51.84 ± 11.43	< 0.001
Etiology
HBV	2409 (71.4)	691 (87.2)	1718 (66.5)	< 0.001
HCV	126 (3.7)	11 (1.4)	115 (4.5)	< 0.001
ALD	649 (19.2)	100 (12.6)	549 (21.3)	< 0.001
AILD	308 (9.1)	39 (4.9)	269 (10.4)	< 0.001
MAFLD	104 (3.1)	69 (8.7)	35 (1.4)	< 0.001
DILD	58 (1.7)	25 (3.2)	33 (1.3)	0.001
MLD	7 (0.2)	2 (0.3)	5 (0.2)	1
Schistosomiasis	49 (1.5)	4 (0.5)	45 (1.7)	0.017
Cryptogenic	169 (5.0)	10 (1.3)	159 (6.2)	< 0.001

HBV: Hepatitis B virus; HCV: Hepatitis C virus; ALD: Alcohol-associated liver disease; MAFLD: Metabolic-associated fatty liver disease; DILD: Drug-induced liver disease; AILD: Autoimmune liver disease; MLD: Metabolic liver disease.

Table 2 Clinical characteristics of acute-on-chronic liver disease patients, n (%)

Characteristic	Overall (n = 3375)	ACLF (n = 850)	non-ACLF
Characteristic	Overall (n = 3375)	ACLF (n = 850)	Overall (n = 2525)	CHAE (n = 577)	LC-A (n = 269)	LC-AD (n = 1679)
Demographics
Sex, male	2489 (73.7)	702 (82.6)	1787 (70.8)^a	431 (74.7)	174 (64.7)^b	1182 (70.4)
Age, yr [median (IQR)]	49.3 (41.6, 58.5)	47.5 (40.0, 55.1)	51.0 (42.7, 59.8)^a	42.2 (33.0, 50.0)	50.2 (43.8, 56.3)^b	53.0 (45.5, 61.4)^c^,^d
Precipitating events
Bacterial infection	771 (22.8)	311 (36.6)	460 (18.2)^a	31 (5.4)	41 (15.2)^b	388 (23.1)^c^,^d
HBV reactivation	378 (11.2)	122 (14.4)	256 (10.1)^a	149 (25.8)	25 (9.29)^b	82 (4.9)^c^,^d
Alcohol intake	327 (9.7)	99 (11.6)	228 (9.0)^a	45 (7.8)	22 (8.18)	161 (9.6)
Superimposed hepatitis viruses	94 (2.8)	46 (5.4)	48 (1.9)^a	18 (3.1)	1 (0.37)	29 (1.7)
Portal vein thrombosis	66 (2.0)	6 (0.7)	60 (2.4)^a	0 (0.0)	1 (0.37)	59 (3.5)^c^,^d
Surgery	40 (1.2)	5 (0.6)	35 (1.4)	1 (0.2)	2 (0.74)	32 (1.9)^d
Drug use	230 (6.8)	94 (11.1)	136 (5.4)^a	55 (9.5)	12 (4.46)	69 (4.1)^d
Physiological exhaustion	138 (4.1)	56 (6.6)	82 (3.3)^a	28 (4.9)	10 (3.72)	44 (2.6)^d
Undefined	925 (27.4)	164 (19.3)	761 (30.1)^a	181 (31.4)	86 (32.0)	494 (29.4)
Complications
HE
Non-overt HE	3080 (91.3)	726 (85.4)	2354 (93.2)	570 (98.8)	265 (98.5)	1519 (90.5)
Grade I-II	233 (6.90)	94 (11.1)	139 (5.50)^a	7 (1.21)	3 (1.12)^b	129 (7.68)^c^,^d
Grade III-IV	62 (1.84)	30 (3.53)	32 (1.27)^a	0 (0.00)	1 (0.37)^b	31 (1.85)^c^,^d
Gastrointestinal bleeding	520 (15.4)	38 (4.47)	482 (19.1)^a	0 (0.00)	0 (0.00)	482 (28.7)^c^,^d
Ascites	1662 (49.2)	515 (60.6)	1147 (45.4)^a	24 (4.16)	6 (2.23)	1117 (66.5)^c^,^d
Biochemical indicators, [median (IQR)]
WBC (× 10⁹/L)	4.91 (3.57, 6.90)	6.61 (4.75, 9.01)	4.49 (3.23, 6.12)^a	4.90 (4.08, 6.09)	4.09 (3.11, 5.48)^b	4.35 (2.95, 6.26)^c^,^d
HGB (g/L)	117 (95.0, 135)	120 (104, 135)	116 (92.0, 135)^a	140 (130, 153)	122 (108, 137)^b	104 (83.0, 122)^c^,^d
PLT (×10⁹/L)	89.0 (56.0, 137)	91.0 (62.0, 129)	89.0 (55.0, 140)	143 (114, 179)	85.0 (59.8, 132)^b	72.0 (48.0, 111)^c^,^d
PT (s)	13.9 (1.69, 18.4)	20.6 (2.57, 26.8)	13.2 (1.45, 16.3)^a	11.8 (1.29, 14.4)	1.90 (1.21, 14.8)	14.2 (1.58, 17.0)^c^,^d
INR	1.44 (1.21, 1.82)	2.13 (1.77, 2.65)	1.32 (1.15, 1.52)^a	1.17 (1.05, 1.34)	1.23 (1.10, 1.46)^b	1.38 (1.22, 1.59)^c^,^d
ALT (IU/mL)	89.0 (32.0, 448)	209 (73.7, 611)	62.3 (27.0, 359)^a	723 (416, 1137)	89.6 (39.8, 252)^b	38.2 (22.4, 80.4)^c^,^d
AST (IU/mL)	114 (47.1, 313)	198 (105, 451)	84.0 (39.2, 258)^a	432 (256, 748)	102 (51.8, 212)^b	54.0 (31.0, 106)^c^,^d
AKP (IU/L)	127 (92.0, 172)	148 (117, 190)	119 (84.7, 164)^a	130 (103, 168)	127 (92.0, 168)	112 (77.0, 161)^c^,^d
GGT (IU/L)	78.8 (38.0, 152)	78.0 (48.6, 127)	79.0 (33.8, 161)^a	151 (97.3, 231)	106 (41.0, 190)^b	54.3 (25.0, 117)^c^,^d
TB (mg/dL)	4.33 (1.68, 13.7)	20.1 (14.1, 27.4)	2.53 (1.33, 5.96)	3.37 (1.71, 8.38)	2.17 (1.34, 3.34)^b	2.44 (1.23, 5.85)^c^,^d
ALB (g/L)	31.7 (27.5, 36.0)	30.7 (27.3, 33.8)	32.1 (27.6, 36.8)^a	38.2 (34.1, 41.5)	33.5 (29.0, 37.4)^b	30.2 (26.3, 34.0)^c^,^d
CRE (mg/L)	0.77 (0.64, 0.94)	0.81 (0.65, 1.08)	0.76 (0.64, 0.91)^a	0.76 (0.64, 0.86)	0.75 (0.61, 0.92)	0.77 (0.64, 0.93)^d
BUN (mmol/L)	4.60 (3.50, 6.60)	4.40 (3.28, 6.60)	4.68 (3.60, 6.60)^a	3.90 (3.12, 4.70)	4.39 (3.70, 5.47)^b	5.30 (3.85, 7.51)^c^,^d
Na (mmol/L)	138 (135, 141)	136 (133, 139)	139 (136, 141)^a	139 (137, 141)	140 (137, 142)	138 (136, 141)^c^,^d
MELD score [median (IQR)]	11.5 (5.92, 18.2)	21.9 (18.5, 25.9)	8.75 (4.60, 13.0)^a	7.79 (3.81, 12.1)	6.56 (3.55, 9.58)^b	9.50 (5.09, 13.7)^c^,^d
Mortality (LT free)
28-d	278 (8.24)	203 (23.9)	75 (2.97)^a	1 (0.17)	2 (0.74)	72 (4.29)^c^,^d
90-d	492 (14.6)	326 (38.4)	166 (6.57)^a	7 (1.21)	8 (2.97)	151 (8.99)^c^,^d

^aP < 0.05 acute-on-chronic liver failure (ACLF) vs non-ACLF.

^bP < 0.05 chronic hepatitis with acute exacerbation (CHAE) vs liver cirrhosis active phase (LC-A).

^cP < 0.05 LC-A vs liver cirrhosis acute decompensation (LC-AD).

^dP < 0.05 CHAE vs LC-AD.

AoCLD: Acute-on-chronic liver disease; CHAE: Chronic hepatitis with acute exacerbation; LC-A: Liver cirrhosis active phase; LC-AD: Liver cirrhosis acute decompensation; ACLF: Acute-on-chronic liver failure; ALD: Alcohol-associated liver disease; MAFLD: Metabolic-associated fatty liver disease; DILI: Drug-induced liver injury; AILD: Autoimmune liver disease; MLD: Metabolic liver disease. LT: Liver transplantation; HE: Hepatic encephalopathy; IQR: Interquartile ranges; HGB: Hemoglobin; PLT: Platelet; PT: Prothrombin time; INR: International normalized ratio; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AKP: Anterior Knee Pain; TB: Total bilirubin; ALB: Albumin; CRE: Creatinine; BUN: Blood urea nitrogen; MELD: Model for end-stage liver disease; WBC: White blood cell; GGT: γ-glutamyl transferase.

Table 3 Characteristics of subtypes of acute-on-chronic liver failure, n (%)

Characteristic	Type A (n = 215)	Type B (n = 100)	Type C (n = 535)
Demographics
Sex, male	175 (81.4)	87 (87.0)	440 (82.2)
Age, yr [median (IQR)]	42.0 (34.0, 49.9)	46.9 (39.7, 54.2)^a	49.2 (43.0, 57.0)^b^,^c
Precipitating events
HBV reactivation	33 (15.3)	11 (11.0)	78 (14.6)
Bacterial infection	54 (25.1)	34 (34.0)	223 (41.7)^b
Alcohol intake	21 (9.77)	8 (8.00)	70 (13.1)
Superimposed hepatitis viruses	13 (6.05)	9 (9.00)	24 (4.49)
Portal vein thrombosis	0 (0.00)	2 (2.00)	4 (0.75)
Surgery	2 (0.93)	0 (0.00)	3 (0.56)
Drug use	29 (13.5)	6 (6.00)	59 (11.0)
Physiological exhaustion	19 (8.84)	7 (7.00)	30 (5.61)
Undefined	55 (25.6)	34 (34.0)	75 (14.0)^b^,^c
Complications
Hepatic encephalopathy
Non-overt HE	186 (86.5)	96 (96.0)	444 (83.0)
Grade I-II	20 (9.30)	3 (3.00)	71 (13.3)^b
Grade III-IV	9 (4.19)	1 (1.00)	20 (3.74)^b
Gastrointestinal bleeding	0 (0.00)	0 (0.00)	38 (7.10)^b^,^c
Ascites	69 (32.1)	10 (10.0)^a	436 (81.5)^b^,^c
Biochemical indicators [median (IQR)]
WBC (× 10⁹/L)	6.84 (5.27, 8.88)	6.23 (4.58, 8.67)	6.66 (4.64, 9.16)
HGB (g/L)	131 (118, 144)	126 (108, 136)^a	116 (98.0, 130)^b^,^c
PLT (× 10⁹/L)	121 (91.0, 154)	89.0 (62.0, 130)^a	80.0 (52.5, 116)^b^,^c
PT (s)	20.2 (2.35, 26.5)	22.5 (19.0, 27.6)^a	20.2 (2.52, 26.6)^b
INR	2.05 (1.72, 2.48)	2.08 (1.76, 2.50)	2.21 (1.81, 2.75)^c
ALT (IU/mL)	531 (200, 1131)	231 (90.7, 607)^a	133 (53.2, 388)^b^,^c
AST (IU/mL)	318 (170, 743)	230 (121, 482)^a	170 (91.0, 342)^b^,^c
AKP (IU/L)	152 (124, 198)	155 (120, 198)	146 (113, 186)
GGT (IU/L)	88.0 (57.0, 141)	82.0 (54.0, 132)	72.0 (43.0, 118)^c
TB (mg/dL)	19.2 (13.7, 25.8)	20.3 (14.2, 25.5)	20.7 (14.2, 28.5)^c
ALB (g/L)	32.1 (29.5, 35.2)	31.4 (28.4, 33.9)^a	29.9 (26.8, 33.1)^b^,^c
CRE (mg/L)	0.77 (0.61, 0.94)	0.75 (0.61, 0.94)	0.86 (0.68, 1.13)^b^,^c
BUN (mmol/L)	3.51 (2.87, 4.55)	3.92 (2.94, 6.05)^a	5.00 (3.65, 8.11)^b^,^c
Na (mmol/L)	137 (135, 140)	137 (133, 140)	136 (131, 138)^b^,^c
MELD score [median (IQR)]	19.9 (17.4, 24.1)	20.7 (17.9, 25.4)	22.6 (19.3, 26.8)^b^,^c
Mortality (LT free)
28-d	38 (17.7)	18 (18.0)	147 (27.5)^b^,^c
90-d	58 (27.0)	36 (36.0)	232 (43.4)^b^,^c

^aP < 0.05, type A vs type B acute-on-chronic liver failure (ACLF).

^bP < 0.05, type B vs type C ACLF.

^cP < 0.05, type A vs type C ACLF.

Citation: Zhang YY, Luo S, Li H, Sun SN, Wang XB, Zheng X, Huang Y, Li BL, Gao YH, Qian ZP, Liu F, Lu XB, Liu JP, Ren HT, Zheng YB, Yan HD, Deng GH, Qiao L, Zhang Y, Gu WY, Xiang XM, Zhou Y, Hou YX, Zhang Q, Xiong Y, Zou CC, Chen J, Huang ZB, Jiang XH, Qi TT, Chen YY, Gao N, Liu CY, Yuan W, Mei X, Li J, Li T, Zheng RJ, Zhou XY, Zhao J, Meng ZJ. Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study. World J Hepatol 2024; 16(5): 809-821
URL: https://www.wjgnet.com/1948-5182/full/v16/i5/809.htm
DOI: https://dx.doi.org/10.4254/wjh.v16.i5.809