Elevated calprotectin levels are associated with mortality in patients with acute decompensation of liver cirrhosis

Table 1 Characteristics of included patients

Parameter	Stable cirrhosis (n = 20)	Acute decompensation (n = 200)	P value
Age (yr), mean ± SD	51.35 ± 12.68	57.29 ± 11.56	0.056
Male gender, n (%)	15 (75.0)	143 (71.5)	0.740
Etiology of cirrhosis1, n (%)
Alcohol	12 (60.0)	106 (53.0)	0.549
Hepatitis C	6 (30.0)	58 (29.0)	0.925
Hepatitis B	3 (15.0)	10 (5.0)	0.102
Cryptogenicautoimmune	2 (10.0)	8 (4.0)	0.229
Autoimmune	0 (0.0)	11 (5.5)	0.605
NASH	0 (0.0)	25 (12.6)	0.139
Other2	2 (10.0)	11 (5.5)	0.335
Active alcoholism, n (%)	0 (0.0)	34 (17.0)	0.049
Prior decompensation, n (%)	15 (75.0)	173 (86.5)	0.182
Laboratory data
Leukocyte count (×109), median	4.96	6.54	0.008
Sodium (mEq/L), mean ± SD	138.05 ± 1.50	136.24 ± 5.21	< 0.001
Creatinine (mg/dL), median	0.8	1.11	< 0.001
INR, median	1.15	1.46	< 0.001
Albumin (g/dL), mean ± SD	3.54 ± 0.34	2.63 ± 0.68	< 0.001
CRP (mg/L), median	3.0	18.2	< 0.001
Total bilirubin (mg/dL), median	1.10	2.20	< 0.001
Calprotectin (ng/dL), median	396.5	477.2	0.127
Child-Pugh score, mean ± SD	6.40 ± 1.60	9.24 ± 1.92	< 0.001
Child-Pugh A, n (%)	13 (65.0)	12 (6.0)	< 0.001
Child-Pugh B, n (%)	6 (30.0)	97 (48.5)	0.114
Child-Pugh C, n (%)	1 (5.0)	91 (45.5)	< 0.001
MELD score, mean ± SD	9.4 ± 1.8	17.6 ± 7.0	< 0.001
Complication at evaluation, n (%)
Ascites	2 (10.0)	125 (62.5)	< 0.001
Hepatic encephalopathy	3 (15.0)	99 (48.5)	< 0.001
Gastrointestinal bleeding	-	66 (33.0)
Bacterial infection	-	70 (35.0)
Alcoholic hepatitis	-	11 (5.5)
CLIF-SOFA, median	-	7.00
ACLF, n (%)	-	56 (28.0)
ACLF grade, n (%)
Grade 1	-	37 (18.5)
Grade 2	-	11 (5.5)
Grade 3	-	8 (4.0)

¹More than one etiologic factor could be present in specific cases.

²Other etiologic factors included primary biliary cirrhosis, sclerosing cholangitis.

NASH: Non-alcoholic steatohepatitis; SD: Standard deviation; INR: International normalized ratio; CRP: C-reactive protein; MELD: Model for end-stage liver disease; CLIF-SOFA: Chronic liver failure - sequential organ failure assessment; ACFL: Acute-on-chronic liver failure.

Table 2 Univariate Cox-regression analysis of factors associated with 30-d mortality among patients hospitalized for acute decompensation of cirrhosis without acute-on-chronic liver failure

Parameter	Survivors (n = 123)	Non-survivors (n = 18)	Univariate analysis
			HR (95%CI)	P value
Age (yr), mean ± SD	55.80 ± 11.67	60.67 ± 9.36	1.039 (0.994–1.085)	0.087
Male gender, n (%)	77 (62.6)	15 (83.3)	2.743 (0.794–9.754)	0.111
Active alcoholism, n (%)	21 (17.1)	2 (11.1)	0.610 (0.140–2.654)	0.510
PPI, n (%)	60 (49.6)	11 (64.7)	1.755 (0.649–4.745)	0.268
Beta-blockers, n (%)	55 (45.5)	7 (41.2)	0.853 (0.325–2.241)	0.747
Prior decompensation, n (%)	104 (84.6)	16 (88.9)	1.409 (0.324–6.129)	0.647
Complication at admission, n (%)
Ascites	60 (48.8)	18 (100.0)	8.588 (2.644–27.898)	0.035
Hepatic encephalopathy	43 (35.0)	13 (72.2)	4.231 (1.508–11.869)	0.006
UGIB	47 (38.2)	5 (27.8)	0.660 (0.235–1.851)	0.429
Bacterial infection	43 (35.0)	11 (61.1)	2.678 (1.038–6.910)	0.042
Laboratory data
Leukocyte count (x109), median	5.51	8.21	1.096 (1.012–1.186)	0.024
Sodium (mEq/L), mean ± SD	137.05 ± 4.45	136.17 ± 6.38	0.962 (0.872–1.060)	0.432
Creatinine (mg/dL), median	1.00	1.02	1.940 (0.525–7.167)	0.320
INR, median	1.39	1.78	2.931 (1.840–4.668)	< 0.001
Albumin (g/dL), mean ± SD	2.65 ± 0.53	2.29 ± 0.92	0.328 (0.140–0.770)	0.010
CRP (mg/L), median	13.15	30.05	1.014 (1.004–1.024)	0.004
Total bilirubin (mg/dL), median	2.00	3.90	1.259 (1.137–1.394)	< 0.001
Calprotectin (ng/mL), median	372.7	838.3	1.018 (1.002–1.034)	0.024
MELD score, mean ± SD	14.10 ± 3.98	20.52 ± 3.85	1.276 (1.168–1.393)	< 0.001
Child-Pugh C, n (%)	38 (30.9)	17 (94.4)	31.205 (4.151–234.60)	< 0.001
CLIF-SOFA, median	6.00	8.00	1.835 (1.419–2.373)	< 0.001
CLIF-C ADs, median	49.07	60.29	1.173 (1.097-1.254)	< 0.001

HR: Hazard ratio; CI: Confidence interval; PPI: Proton-pump inhibitor; UGIB: Upper gastrointestinal bleeding, INR: International normalized ratio; CRP: C-reactive protein; ACFL: Acute-on-chronic liver failure; MELD: Model for end-stage liver disease; CLIF-SOFA: Chronic liver failure - sequential organ failure assessment; CLIF-C ADs: Chronic liver failure consortium acute decompensation score.