Acute-on-chronic liver failure in a multi-ethnic Asian city: A comparison of patients identified by Asia-Pacific Association for the Study of the Liver and European Association for the Study of the Liver definitions

Table 1 Profile of patients with acute-on-chronic liver failure n (%)

	APASL only (n = 14)	EASL only (n = 15)	Both (n = 49)	P value3	Total (n = 78)
AGE (mean)	53 (48-57)	66 (61-71)	57 (54-60)	0.003	58 (55-61)
Race
Chinese	9 (64.3)	9 (60)	36 (73.5)	0.171	54 (69.2)
Malay	1 (7.1)	2 (13.3)	5 (10.2)		8 (10.3)
Indian	0	3 (20)	5 (10.2)		8 (10.3)
Others	4 (28.6)	1 (6.7)	3 (6.1)		8 (10.3)
Male gender	12 (85.7)	11 (73.3)	36 (73.5)	0.625	59 (75.6)
Diabetes mellitus	7 (50)	5 (33.3)	16 (32.7)	0.478	28 (35.9)
Cause of acute liver injury4
Infection	4 (28.6)	14 (93.3)	28 (57.1)	0.002	46 (59)
Hepatitis B flare	9 (64.3)	0	14 (28.6)	0.001	23 (29.5)
Variceal bleeding	4 (28.6)	2 (13.3)	13 (26.5)	0.535	19 (24.4)
Unknown cause	2 (14.3)	1 (6.7)	8 (16.3)	0.642	11 (14.1)
Alcohol	1 (7.1)	0	5 (10.2)	0.429	6 (7.7)
TCM	1 (7.1)	0	5 (10.2)	0.429	6 (7.7)
TIPSS	0	0	1 (2)	0.741	1 (1.3)
Underlying chronic liver disease
Hepatitis B	11 (78.6)	1 (6.7)	22 (44.9)	< 0.0001	34 (43.6)
Alcohol	2 (14.3)	3 (20)	11 (22.4)	0.799	16 (20.5)
Cryptogenic	0	3 (20)	6 (12.2)	0.234	9 (11.5)
Hepatitis C	0	2 (13.3)	3 (6.1)	0.339	5 (6.4)
NASH	0	2 (13.3)	2 (4.1)	0.23	4 (5.1)
Hepatitis B + alcohol	1 (7.1)	0	1 (2)	0.444	2 (2.6)
Others1	0	4 (26.7)	5 (10.2)	0.072	9 (11.5)
Liver cirrhosis	6 (42.9)	15 (100)	49 (100)	< 0.0001	70 (89.7)
HCC (Milan’s criteria)	0	1 (6.7)	4 (8.2)	0.627	5 (6.4)
Other cancers2	0	1 (6.7)	4 (8.2)		5 (6.4)
No malignancy	14 (100)	13 (86.7)	41 (83.7)		68 (87.2)
Previous decompensation	4 (28.6)	10 (66.7)	20 (43.5)	0.11	34 (45.3)

¹Other chronic liver diseases include Wilson's disease, Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis, Congenital fibrosis, Drug-induced chronic liver disease and autoimmune liver disease;

²Other cancers: Colon cancer, renal cell carcinoma, bladder cancer and ovarian cancer;

³P-value of comparison of patients falling under APASL, EASL and both criteria;

⁴Patients may have more than one cause of acute liver injury. TCM: Traditional Chinese Medicine; TIPSS: Transjugular intrahepatic portosystemic shunt; NASH: Non-alcoholic steatohepatitis; HCC: Hepatocellular carcinoma; APASL: Asia-Pacific Association for the Study of the Liver; EASL: European Association for the Study of the Liver.

Table 2 Outcome of patients with acute-on-chronic liver failure n (%)

	APASL only (n = 14)	EASL only (n = 15)	Both (n = 49)	P value	Total (n = 78)
MELD score (mean-range)	27 (23-31)	18 (13-23)	25 (22-28)	0.020	24 (33-26)
Transplant	4 (28.6)	0	7 (14.6)	0.089	11 (14.3)
Mortality (during admission)	4 (28.6)	8 (53.3)	33 (67.3)	0.033	45 (57.7)
Three month mortality	5 (35.7)	8 (53.3)	35 (71.4)	0.041	48 (61.5)

P value of comparison of patients falling under APASL, EASL and both criteria. APASL: Asia-Pacific Association for the Study of the Liver; EASL: European Association for the Study of the Liver.

Table 3 Organ failures, laboratory parameters and outcome of acute-on-chronic liver failure patients with respect to acute-on-chronic liver failure grade n (%)

	ACLF0 (n = 6)	ACLF1 (n = 7)	ACLF2 (n = 24)	ACLF3 (n = 33)1	P value
Organ failures-clif-sofa score
Liver	1 (16.7)	1 (14.3)	12 (50)	27 (81.8)	< 0.0001
Kidney	0	4 (57.1)	10 (41.7)	25 (75.8)	0.002
Cerebral	0	1 (14.3)	2 (8.3)	13 (39.4)	0.018
Coagulation	1 (16.7)	1 (14.3)	16 (66.7)	25 (75.8)	0.002
Circulation	0	0	7 (30.4)	26 (78.8)	< 0.0001
Respiration	0	0	2 (8.3)	7 (21.2)	0.22
Chronic renal disease	0	2 (28.6)	5 (20.8)	3 (9.1)	0.245
Laboratory data (mean)
Leucocyte count at baseline, × 109/L	8 (6-11)	11 (6-16)	10 (7-12)	12 (10-13)	0.256
Platelet count at baseline	127 (42-212)	61 (40-82)	104 (78-129)	149 (105-193)	0.105
Bilirubin at baseline, mg/dL	7.0 (4.2-9.8)	7.7 (-3.1-18.5)	10 (4.9-15.1)	13.9 (9.9-17.8)	0.29
Peak bilirubin, mg/dL	11.3 (4.1-18.5)	10.7 (-4.2-25.5)	14.1 (9.1-19)	23 (18.7-27.3)	0.009
Creatinine at baseline, mg/dL	0.9 (0.4-1.3)	2.1 (1.3-2.9)	1.4 (1.1-1.8)	1.8 (1.1-2.4)	0.232
Peak creatinine, mg/dL	0.9 (0.5-1.2)	2.2 (1.4-3.1)	1.8 (1.4-2.1)	3.1 (2.6-3.7)	< 0.0001
Lactate at baseline, mmol/L	2.1 (1.4-2.7)	2.3 (2.1-2.6)	2.4 (1.7-3.2)	4.1 (2.4-5.7)	0.225
MELD score at baseline (mean)	23 (20-26)	21 (11-31)	20 (17-24)	26 (23-30)	0.113
Liver transplantation	1 (16.7)	0	6 (26.1)	1 (3)	0.043
Mortality during admission	0	3 (42.9)	10 (41.7)	28 (84.8)	< 0.0001
90-d mortality	0	3 (42.9)	11 (45.8)	29 (87.9)	< 0.0001

¹Only patients with cirrhosis were included in this analysis. P-value of comparison of patients with ACLF grade 0, 1, 2 and 3. ACLF: Acute-on-chronic liver failure.

Table 4 Demographics, type of organ failure and laboratory parameters of acute-on-chronic liver failure patients with respect to outcome n (%)

	Deaths (n = 45)	Survivors (n = 33)	P value
Age (mean-range)	60 (56-64)	55 (52-58)	0.0441
Liver transplantation	0	11 (34.4)	< 0.00012
Race
Chinese	33 (73.3)	21 (63.6)	0.0041
Malay	6 (13.3)	2 (6.1)
Indian	6 (13.3)	2 (6.1)
Others	0	8 (24.2)
Male gender	33 (73.3)	26 (78.8)	0.5791
Diabetes mellitus	13 (28.9)	15 (45.5)	0.1321
Previous hepatic decompensation	16 (37.2)	18 (56.2)	0.1011
Potential events leading to acute insult
Infection	28 (62.2)	18 (54.5)	0.4961
Hepatitis B flare	15 (33.3)	8 (24.2)	0.3841
Variceal bleeding	10 (22.2)	9 (27.3)	0.6081
Unknown cause	5 (11.1)	6 (18.2)	0.2872
Alcohol	2 (4.4)	4 (12.1)	0.2042
TCM	5 (11.1)	1 (3)	0.1892
TIPSS	1 (2.2)	0	0.5772
Underlying chronic liver disease
Hepatitis B	20 (44.4)	14 (42.4)	0.8591
Alcohol	10 (22.2)	6 (18.2)	0.6621
Cryptogenic	4 (8.9)	5 (15.2)	0.3072
Hepatitis C	3 (6.7)	2 (6.1)	0.6462
NASH	2 (4.4)	2 (6.1)	0.5672
Hepatitis B + alcohol	1 (2.2)	1 (3)	0.6702
Others1	6 (13.3)	3 (9.1)	0.4192
Liver cirrhosis	41 (91)	29 (87.9)	0.4592
HCC+ (Milan criteria)	3 (6.7)	2 (6.1)	0.7092
Other cancers2	2 (4.4)	3 (9.1)
None	40 (88.9)	28 (84.8)
Organ failures-clif-sofa score
Liver	31 (68.9)	17 (51.5)	0.1191
Kidney	31 (68.9)	10 (30.3)	0.0011
Cerebral	17 (37.8)	4 (12.1)	0.0121
Coagulation	31 (68.9)	19 (57.6)	0.3031
Circulation	28 (63.6)	7 (21.2)	< 0.00011
Respiration	8 (17.8)	1 (3)	0.0442
Chronic renal disease	9 (20)	2 (6.1)	0.0752
Leucocyte count at baseline (mean-range)	11 (10-12)	10 (8-12)	0.2733
Platelet count at baseline (mean-range)	135 (109-160)	120 (79-160)	0.5283
Amylase (mean-range)	117 (90-144)	72 (38-105)	0.0263
Maximal total bilirubin (mean-range)	20.2 (16.3-24)	15.9 (11.5-20.2)	0.1373
Maximal creatinine (mean-range)	2.9 (2.4-3.3)	1.6 (1.3-1.9)	< 0.00013
Maximal INR (mean-range)	4.3 (3.5-5.1)	3 (2.5-3.6)	0.0183
MELD at baseline (mean-range)	26 (23-29)	22 (19-25)	0.1193
Lactate at baseline (mean-range)	3.5 (2.4-4.6)	2.8 (2-3.7)	0.3113

¹χ² test;

²Fisher exact test;

³Independent t-test. TCM: Traditional Chinese Medicine; TIPSS: Transjugular intrahepatic portosystemic shunt; NASH: Non-alcoholic steatohepatitis; HCC: Hepatocellular carcinoma; APASL: Asia-Pacific Association for the Study of the Liver; EASL: European Association for the Study of the Liver.