Erhöhte Lipasewerte beim akut-auf-chronischen Leberversagen (ACLF) sind mit einer erhöhten Mortalität assoziiert

Einleitung Das akute-auf-chronische Leberversagen (ACLF) ist durch die akute Dekompensation einer chronischen Lebererkrankung, das Auftreten von Organversagen und eine hohe kurzfristige Mortalität gekennzeichnet. Trotz gemeinsamer Risikofaktoren für Leber- und Pankreasschädigung wie Alkohol- oder Medikamentenmissbrauch, bleibt die Rolle der Bauchspeicheldrüse beim ACLF wenig erforscht. Diese Studie untersuchte Prävalenz, Dynamik und prognostische Bedeutung erhöhter Lipase- (eLIP) und (Alpha-)Amylasewerte (eAMY) im ACLF ([Abb. 1] [2] [3]).

Abb. 1  

Abb. 2  

Abb. 3  

Material und Methodik Retrospektiv wurden ACLF-Patienten (EASL-CLIF-Kriterien) am Allgemeinen Krankenhaus Wien (11/2003–11/2022) identifiziert. eLIP und eAMY wurden als Werte≥3-fach der oberen Grenze des Normbereichs (ULN) definiert. Labor- und klinische Daten wurden 30–365 Tage vor ACLF, bei Diagnose (D0), Tag 7 (D7), 28 (D28) und 90 (D90) nach Diagnosestellung erhoben. Cox-Proportional-Hazard-Modelle wurden für klinisch relevante Kofaktoren zu D0 bzw. D7 adjustiert (1: Alter, Geschlecht, Lebervenendruckgradienten (HVPG), Albumin, C reaktives Protein, MELD Na-Score; 2: Geschlecht, HVPG, CLIF-C ACLF score).

Ergebnisse Von 193 ACLF-Patienten (G1: 47,7%, G2: 32,1%, G3: 20,2%) hatten 43,5% erhöhte Lipase- und 50,2% erhöhte (Alpha-)Amylase-Werte, welche stark korrelierten (Spearman’s Rho: 0,687; p<0,001). eLIP wurde bei 8,8% an D0 und 15,7% an D7 beobachtet, während 3 Patienten klinische/radiologische Pankreatitis-Zeichen zeigten. MAP<70 mmHg (OR: 4,41; p=0,048) und Nierenversagen (nach EASL-CLIF, OR: 6,31; p=0,030) waren mit eLIP zu D0 assoziiert. Pankreasenzymwerte an D0 waren nicht mit Mortalität assoziiert (alle p>0,05). eLIP an D7 war ein unabhängiger Risikofaktor für Mortalität zu D28 (aHR: 2,15; p=0,031) und D90 (aHR: 2,14; p=0,011). Neu aufgetretene eLIP zu D7 war prognostisch besonders relevant (Mortalität D28: aHR: 4,35; p<0,001; D90: aHR: 4,19; p<0,001), auch nach Adjustierung auf den CLIF-C ACLF score zu D7 (D28: OR: 1,99; p=0,038; D90: OR: 2,19; p=0,012).

Zusammenfassung Erhöhte Pankreasenzymwerte treten beim ACLF häufig auf, auch ohne klinische Zeichen einer Pankreatitis. Lipasewerte≥3-fach des ULN am D7 sind mit einer erhöhten ACLF-Mortalität assoziiert ([Table 1] [2]).

Table 1 Patient characteristics.

	Overall	ACLF-1	ACLF-2	ACLF-3	p-value
Patients (n,%)	193	92 (47.67%)	62 (32.12%)	39 (20.21%)
Age, years (mean, SD)	56.64±11.73	59.56±10.95	55.87±11.14	50.96±12.4	0.001
Sex, n (%)					0.876
Male	122 (63.21%)	57 (62%)	39 (62.9%)	26 (66.7%)
Female	71 (36.79%)	35 (38%)	23 (37.1%)	13 (33.3%)
Etiology (n,%)					0.585
ALD	101 (52.3%)	52 (56.5%)	33 (53.2%)	16 (41%)
Viral hepatitis	32 (16.6%)	15 (16.3%)	9 (14.5%)	8 (20.5%)
ALD+viral hepatitis	7 (3.6%)	4 (4.3%)	1 (1.6%)	2 (5.1%)
MASLD	16 (8.3%)	7 (7.6%)	5 (8.1%)	4 (10.3%)
Cholestatic	8 (4.1%)	2 (2.2%)	2 (3.2%)	4 (10.3%)
Other	29 (15%)	12 (13%)	12 (19.4%)	5 (12.8%)
Pre-ACLF
Varices (n,%)					0.209
none	37 (19.17%)	14 (15.2%)	14 (22.6%)	9 (23.1%)
small	55 (28.50%)	33 (35.9%)	12 (19.4%)	10 (25.6%)
large	84 (43.52%)	41 (44.6%)	30 (48.4%)	13 (33.3%)
Splenomegaly (n,%)	142 (73.58%)	67 (72.8%)	47 (75.8%)	28 (71.8%)	0.519
VCTE-LSM (kPa)	49.6 (30.5-73.5)	53.3 (29.75-72.75)	58.2 (26.48-75)	42.85 (33.22-70.95)	0.803
HVPG (mmHg)	19 (16-23)	20 (17-23)	19 (16-23)	18 (14.25-21)	0.080
MELD-Na score (points)	19 (16-23)	19 (13-22.75)	20 (16-23)	19 (16-23)	0.339
Child-Turcotte-Pugh Score (points)	9 (8-10.75)	9 (7-10)	9 (8-10)	10 (8-11)	0.356
At ACLF-diagnosis (D0)
Organ failure (as per EASL-CLIF) (n,%)
Liver	49 (25.39%)	11 (12%)	22 (35.5%)	16 (41%)	<0.001
Kidney	128 (66.32%)	58 (63%)	42 (67.7%)	28 (71.8%)	0.600
Respiration	30 (15.54%)	1 (1.1%)	4 (6.5%)	25 (64.1%)	<0.001
Circulation	49 (25.39%)	1 (1.1%)	14 (22.6%)	34 (87.2%)	<0.001
Brain	77 (39.90%)	19 (20.7%)	27 (43.5%)	31 (79.5%)	<0.001
Coagulation	30 (15.54%)	3 (3.3%)	15 (24.2%)	12 (30.8%)	<0.001
MELD-Na score (points)	28 (24-32)	26 (22-29)	29 (25-33)	31 (27-36)	<0.001
Child-Turcotte-Pugh Score (points)	11 (9-13)	10 (9-11)	11.5 (10-13)	13 (12-13)	<0.001
CLIF-C ACLF Score (points)	47.37 (41.68-54.23)	42.98 (39.19-48.47)	48.49 (43.31-52.4)	59.78 (55.54-64.54)	<0.001
Lipase (U/L)	54 (27-87)	44.5 (25.25-84.5)	56.5 (32.75-91)	57 (25.5-81.5)	0.575
Alpha-Amylase (U/L)	63 (38-94.25)	66 (38-95.75)	61 (36-92)	66 (43-95)	0.831
Creatinine (mg/dL)	2.14 (1.50-2.68)	2.14 (1.64-2.36)	2.2 (1.39-2.84)	2.09 (1.44-2.65)	0.904
Blood Urea Nitrogen (mg/dL)	44.6 (29.4-63.8)	46.25 (31.17-61.05)	44.05 (29.12-69)	42 (24.15-62.85)	0.883
Bilirubin (mg/dL)	4.81 (1.60-12.36)	2.77 (1.27-5.96)	5.19 (1.71-15.92)	8.08 (4.82-20.8)	<0.001
Albumin (g/L)	27.1 (22.8-31.7)	28.6 (24.08-32.45)	26 (22.8-31.4)	25 (22.4-28.65)	0.024
INR	1.68 (1.36-2.16)	1.55 (1.26-1.9)	1.71 (1.3-2.35)	1.9 (1.64-2.7)	<0.001
CRP (mg/dL)	2.87 (1.23-7.7)	2.66 (1.22-6.49)	2.63 (1.16-7.44)	6.5 (1.33-11.53)	0.149
D7 post ACLF-diagnosis
Organ failure (as per EASL-CLIF) (n,%)
Liver	44 (22.8%)	10 (10.9%)	21 (33.9%)	13 (33.3%)	<0.001
Kidney	70 (36.3%)	29 (31.5%)	27 (43.5%)	14 (35.9%)	0.313
Respiration	31 (16.0%)	7 (7.6%)	8 (12.9%)	16 (41%)	<0.001
Circulation	52 (26.9%)	13 (14.1%)	21 (33.9%)	18 (46.2%)	<0.001
Brain	45 (23.3%)	12 (13%)	14 (22.6%)	19 (48.7%)	<0.001
Coagulation	28 (14.5%)	10 (10.9%)	11 (17.7%)	7 (17.9%)	0.391
MELD-Na score (points)	25 (20–31)	23.21±7.92	27.66±7.59	27.85±7.91	0.002
Child-Turcotte-Pugh Score (points)	11 (9-13)	10 (8-11)	11 (10-13)	13 (12-14)	<0.001
CLIF-C ACLF Score (points)	47.37 (41.68–54.23)	39.86 (35.14-47.75)	46.5 (38.9-57.13)	59.86 (47.4-68.13)	<0.001
Lipase (U/L)	61 (34.50-118)	61 (37-111)	56 (30-122.5)	65 (34-126)	0.844
Alpha-Amylase (U/L)	61 (40-105)	76 (42-103)	55 (33.5-111.5)	55 (35-93)	0.319
Creatinine (mg/dL)	1.46 (1-2.33)	1.46 (1.01-2.23)	1.6 (1.04-2.74)	1.15 (0.95-1.83)	0.159
Blood Urea Nitrogen (mg/dL)	39.50 (21.70-61.80)	36.15 (21.45-53.8)	49.1 (23.95-64.42)	35.4 (21.75-48.75)	0.218
Bilirubin (mg/dL)	5.56 (1.84-12.12)	2.63 (1.2-7.15)	6.92 (2.13-14.54)	11.71 (6.32-17.52)	<0.001
Albumin (g/L)	28.70 (25.30-32.65)	29.1 (25.55-33.48)	28.7 (24.58-32.55)	27.1 (25.15-29.65)	0.115
INR	1.70 (1.33-2.28)	1.53 (1.29-1.9)	1.77 (1.4-2.4)	1.84 (1.44-2.54)	0.015
CRP (mg/dL)	3.05 (1.39-6.05)	2.17 (0.89-5.08)	4.17 (1.98-6.36)	4.34 (2.19-6.58)	0.011

Data expressed as n (%), mean±standard deviation (SD) or median (IQR). Between ACLF grades, continuous variables were analyzed using either one-way ANOVA and Kruskal-Wallis tests, depending on whether the data followed a normal distribution with post hoc correction performed via Tukey’s test for ANOVA and Dunn’s test for Kruskal-Wallis. Categorical variables were compared using Pearson’s Chi-squared test or Fisher’s exact test. Abbreviations: ALD, Alcohol-related liver disease; HVPG, hepatic venous pressure gradient; INR, international normalized ratio; MASLD, Metabolic dysfunction- associated steatotic liver disease; MELD, model for end-stage liver disease; VCTE-LSM, vibration-controlled transient elastography liver stiffness measurement. P-values in bold indicate statistical significance.

Table 2 Risk factors for D28 mortality.

	Univariate Cox proportional hazard model			Multivariate Cox proportional hazard model
	HR	95% CI	p-value	aHR	95% CI	p-value
Model 1 – Risk factors at D0
Age, per year	0.99	0.97-1.01	0.517	1.02	0.99-1.04	0.141
Sex, male	1.03	0.64-1.63	0.916	0.88	0.54-1.42	0.594
HVPG, per mmHg	1.01	0.97-1.05	0.744	1.01	0.97-1.05	0.714
MELD-Na, per point	1.13	1.08-1.18	<0.001	1.14	1.09-1.20	<0.001
Albumin, per g/dL	0.96	0.93-0.99	0.011	0.99	0.95-1.02	0.435
CRP, per md/dL	1.03	1.00-1.07	0.031	1.03	1.00-1.07	0.037
Lipase≥180 U/L, binary	0.82	0.36-1.89	0.647	0.63	0.25-1.60	0.334
Model 2 – Risk factors at D7
Age, per year	0.99	0.97-1.01	0.517	1.02	0.99-1.05	0.144
Sex, male	1.03	0.64-1.63	0.916	0.63	0.35-1.15	0.133
HVPG, per mmHg	1.01	0.97-1.05	0.744	0.97	0.92-1.03	0.320
MELD-Na, per point	1.17	1.12-1.22	<0.001	1.20	1.14-1.25	<0.001
Albumin, per g/dL	0.95	0.92-0.99	0.010	0.99	0.95-1.04	0.758
CRP, per md/dL	1.08	1.02-1.15	0.007	1.05	0.97-1.13	0.214
Lipase≥180 U/L, binary	2.16	1.16-4.05	0.016	2.15	1.07-4.30	0.031
Model 3 – Risk factors at D7
Age, per year	0.99	0.97-1.01	0.517	1.01	0.99-1.04	0.246
Sex, male	1.03	0.64-1.63	0.916	0.57	0.31-1.03	0.063
HVPG, per mmHg	1.01	0.97-1.05	0.744	0.98	0.92-1.04	0.440
MELD-Na, per point	1.17	1.12-1.22	<0.001	1.21	1.15-1.27	<0.001
Albumin, per g/dL	0.95	0.92-0.99	0.010	1.05	0.98-1.13	0.173
CRP, per md/dL	1.08	1.02-1.15	0.007	0.99	0.95-1.03	0.624
De-novo eLIP at D7, binary	3.18	1.63-6.19	<0.001	4.35	2.13-8.87	<0.001

Uni- and multivariate Cox proportional hazard models were used to evaluate predictors of D28 mortality. Each model incorporated a single of the assessed risk factors (“interchangeable variates”) alongside indicated fixed covariates. The results are presented as HRs or aHRs, along with 95% CIs and p values. Abbreviations: aHR, adjusted HR; CRP, C-reactive protein; HR, hazard ratio; HVPG, hepatic venous pressure gradient; MELD: model for end-stage liver disease. P-values in bold indicate statistical significan

 

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Publication History

Article published online:
13 May 2025