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DOI: 10.1055/s-0045-1809245
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]).
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]).
|
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.
|
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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13. Mai 2025
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